tag:theconversation.com,2011:/us/topics/telomeres-4831/articlesTelomeres – The Conversation2022-11-10T19:01:30Ztag:theconversation.com,2011:article/1942342022-11-10T19:01:30Z2022-11-10T19:01:30ZHow cancer cells can become immortal – research finds a mutated gene that helps melanoma defeat the normal limits on repeated replication<figure><img src="https://images.theconversation.com/files/494498/original/file-20221109-2908-x151bw.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3295%2C2608&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Melanoma is a particularly aggressive form of skin cancer.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/melanoma-cancer-cell-royalty-free-image/177233874">Dlumen/iStock via Getty Images Plus</a></span></figcaption></figure><p>A defining characteristic of cancer cells is their <a href="https://doi.org/10.1016/S0092-8674(00)81683-9">immortality</a>. Usually, normal cells are limited in the number of times they can divide before they stop growing. Cancer cells, however, can overcome this limitation to form tumors and bypass “mortality” by continuing to replicate. </p>
<p><a href="https://doi.org/10.1038/345458a0">Telomeres</a> play an essential role in determining how many times a cell can divide. These repetitive sequences of DNA are located at the ends of chromosomes, structures that contain genetic information. In normal cells, continued rounds of replication shorten telomeres until they become so short that they eventually trigger the cell to stop replicating. In contrast, tumor cells can maintain the lengths of their telomeres by activating an enzyme called <a href="https://doi.org/10.1186/s12929-018-0422-8">telomerase</a> that rebuilds telomeres during each replication.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/494502/original/file-20221109-16-a949gi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of chromosome with red telomeres at the ends" src="https://images.theconversation.com/files/494502/original/file-20221109-16-a949gi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/494502/original/file-20221109-16-a949gi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=655&fit=crop&dpr=1 600w, https://images.theconversation.com/files/494502/original/file-20221109-16-a949gi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=655&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/494502/original/file-20221109-16-a949gi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=655&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/494502/original/file-20221109-16-a949gi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=823&fit=crop&dpr=1 754w, https://images.theconversation.com/files/494502/original/file-20221109-16-a949gi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=823&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/494502/original/file-20221109-16-a949gi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=823&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Telomeres are protective caps at the ends of chromosomes.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/telomere-is-the-end-of-a-chromosome-royalty-free-illustration/916486974">FancyTapis/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>Telomerase is encoded by a gene called <a href="https://www.ncbi.nlm.nih.gov/gene/7015">TERT</a>, one of the most frequently mutated genes in cancer. TERT mutations cause cells to <a href="https://doi.org/10.1126/science.279.5349.349">make a little too much telomerase</a> and are thought to help cancer cells keep their telomeres long even though they replicate at high rates. <a href="https://www.cancer.org/cancer/melanoma-skin-cancer/about/what-is-melanoma.html">Melanoma</a>, an aggressive form of skin cancer, is highly dependent on telomerase to grow, and <a href="https://doi.org/10.1126/science.1230062">three-quarters</a> <a href="https://doi.org/10.1126/science.1229259">of all melanomas</a> acquire mutations in telomerase. These same TERT mutations also occur across <a href="https://doi.org/10.1158/1541-7786.MCR-16-0003">other cancer types</a>.</p>
<p>Unexpectedly, researchers found that TERT mutations could <a href="https://doi.org/10.1126/science.aao0535">only partially explain</a> the longevity of telomeres in melanoma. While TERT mutations did indeed extend the life span of cells, they did not make them immortal. That meant there must be something else that helps telomerase allow cells to grow uncontrollably. But what that “second hit” might be has been unclear.</p>
<p>We are researchers who study the role telomeres play in <a href="https://scholar.google.com/citations?user=ViGpANMAAAAJ&hl=en">human health and diseases</a> like <a href="https://scholar.google.com/citations?user=lUDPKTEAAAAJ&hl=en">cancer</a> in the Alder Lab at the University of Pittsburgh. While investigating the ways that tumors maintain their telomeres, we and our colleagues found another piece to the puzzle: <a href="https://www.science.org/doi/10.1126/science.abq0607">another telomere-associated gene</a> in melanoma.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/QVCjdNxJreE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Cancer is a result of uncontrollable cell growth.</span></figcaption>
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<h2>Cell immortality gets a boost</h2>
<p>Our team focused on melanoma because this type of cancer is linked to people with <a href="https://doi.org/10.1172/jci120851">long telomeres</a>. We examined DNA sequencing data from hundreds of melanomas, looking for mutations in genes related to telomere length. </p>
<p>We identified a cluster of mutations in a gene called <a href="https://medlineplus.gov/genetics/gene/tpp1/">TPP1</a>. This gene codes for one of the six proteins that form a molecular complex called <a href="https://doi.org/10.1101/gad.1346005">shelterin</a> that coats and protects telomeres. Even more interesting is the fact that TPP1 is known to <a href="https://doi.org/10.1038/nature05454">activate telomerase</a>. Identifying the TPP1 gene’s connection to cancer telomeres was, in a way, obvious. After all, it was <a href="https://doi.org/10.1038/nature05454">more than a decade ago</a> that researchers showed that TPP1 would increase telomerase activity.</p>
<p>We tested whether having an excess of TPP1 could make cells immortal. When we introduced just TPP1 proteins into cells, there was no change in cell mortality or telomere length. But when we introduced TERT and TPP1 proteins at the same time, we found that they worked synergistically to cause significant telomere lengthening. </p>
<p>To confirm our hypothesis, we then inserted TPP1 mutations into melanoma cells using CRISPR-Cas9 genome editing. We saw an increase in the amount of TPP1 protein the cells made, and a subsequent increase in telomerase activity. Finally, we returned to the DNA sequencing data and found that 5% of all melanomas have a mutation in both TERT and TPP1. While this is still a significant proportion of melanomas, there are likely other factors that contribute to telomere maintenance in this cancer.</p>
<p><a href="https://www.science.org/doi/10.1126/science.abq0607">Our findings</a> imply that TPP1 is likely one of the missing puzzle pieces that boost telomerase’s capacity to maintain telomeres and support tumor growth and immortality.</p>
<h2>Making cancer mortal</h2>
<p>Knowing that cancer use these genes in their replication and growth means that researchers could also block them and potentially stop telomeres from lengthening and make cancer cells mortal. This discovery not only gives scientists another potential avenue for cancer treatment, but also draws attention to an underappreciated class of mutations outside the traditional boundaries of genes that can play a role in cancer diagnostics.</p><img src="https://counter.theconversation.com/content/194234/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jonathan Alder receives funding from the National Heart, Lung, and Blood Institute to support this work. </span></em></p><p class="fine-print"><em><span>Pattra Chun-On does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>One enzyme plays a key role in how tumor cells replicate and divide indefinitely. Identifying the genes that give these cells their immortality could provide new drug targets to treat cancer.Pattra Chun-On, Ph.D. Candidate in Environmental and Occupational Health, University of PittsburghJonathan Alder, Assistant Professor of Medicine, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1864452022-07-19T12:25:44Z2022-07-19T12:25:44ZCells become zombies when the ends of their chromosomes are damaged – a tactic both helpful and harmful for health<figure><img src="https://images.theconversation.com/files/473984/original/file-20220713-9184-rhhs18.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3000%2C2213&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Telomeres (red) at the ends of chromosomes protect your DNA from damage.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/JUr1Ay">Thomas Ried/NCI Center for Cancer Research, National Cancer Institute, National Institutes of Health via Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>Damage to the ends of your chromosomes can create “zombie cells” that are still alive but can’t function, according to our recently published study in <a href="https://doi.org/10.1038/s41594-022-00790-y">Nature Structural and Molecular Biology</a>.</p>
<p>When cells prepare to divide, their DNA is tightly wound around proteins to form chromosomes that provide structure and support for genetic material. At the ends of these chromosomes are repetitive stretches of DNA called <a href="https://www.genome.gov/genetics-glossary/Telomere">telomeres</a> that form a protective cap to prevent damage to the genetic material. However, telomeres shorten each time a cell divides. This means that as cells divide more and more as you age, your telomeres become increasingly shorter and more likely to lose their ability to protect your DNA.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/474165/original/file-20220714-32290-qampef.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram depicting chromosomes in the nucleus, highlighting the telomeres at the ends of each DNA-containing arm." src="https://images.theconversation.com/files/474165/original/file-20220714-32290-qampef.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/474165/original/file-20220714-32290-qampef.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=381&fit=crop&dpr=1 600w, https://images.theconversation.com/files/474165/original/file-20220714-32290-qampef.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=381&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/474165/original/file-20220714-32290-qampef.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=381&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/474165/original/file-20220714-32290-qampef.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=479&fit=crop&dpr=1 754w, https://images.theconversation.com/files/474165/original/file-20220714-32290-qampef.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=479&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/474165/original/file-20220714-32290-qampef.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=479&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Telomeres serve as protective caps at the ends of each chromosome.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/telomere-chromosome-and-dna-royalty-free-illustration/961320764">FancyTapis/iStock via Getty Images</a></span>
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<p>Damage to genetic material can lead to mutations that cause cells to divide uncontrollably, resulting in cancer. Cells avoid becoming cancerous when their telomeres become too short after dividing too many times and potentially accruing damage along the way, however, by entering a zombielike state that stops cells from from dividing through a process called <a href="https://doi.org/10.7554/eLife.72449">cellular senescence</a>.</p>
<p>Because they are resistant to death, senescent – or “zombie” – cells accumulate with age. They can be beneficial to health by promoting senescence in nearby cells at risk of becoming cancerous and attracting immune cells to clear out cancer cells. But they can also contribute to disease by impairing tissue healing and immune function, and by secreting chemicals that promote inflammation and tumor growth.</p>
<p>We wanted to know if direct damage to telomeres can be sufficient to trigger senescence and make zombie cells. In order to figure this out, we needed to confine damage just to the telomeres. So we attached a protein to the telomeres of human cells grown in the lab. Then we added a dye to the protein that makes it sensitive to light. Shining a far-red light (or light with a wavelength slightly shorter than infrared light) on the cells induces the protein to produce oxygen <a href="https://www.verywellhealth.com/information-about-free-radicals-2249103">free radicals</a> – highly reactive molecules that can damage DNA – right at the telomeres, sparing the rest of the chromosome and the cell.</p>
<p>We found that direct damage to the telomeres was sufficient to turn cells into zombies, even when these protective caps weren’t shortened. The reason for this, we discovered, was likely a result of <a href="https://doi.org/10.1038%2Fncb2897">disrupted DNA replication</a> at the telomeres that leaves chromosomes even more susceptible to damage or mutations. </p>
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<a href="https://images.theconversation.com/files/473987/original/file-20220713-13035-8w2uvc.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of chromosomes with telomeres damaged by oxidation" src="https://images.theconversation.com/files/473987/original/file-20220713-13035-8w2uvc.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/473987/original/file-20220713-13035-8w2uvc.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=348&fit=crop&dpr=1 600w, https://images.theconversation.com/files/473987/original/file-20220713-13035-8w2uvc.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=348&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/473987/original/file-20220713-13035-8w2uvc.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=348&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/473987/original/file-20220713-13035-8w2uvc.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=437&fit=crop&dpr=1 754w, https://images.theconversation.com/files/473987/original/file-20220713-13035-8w2uvc.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=437&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/473987/original/file-20220713-13035-8w2uvc.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=437&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The telomeres (green) at the tips of chromosomes (blue) damaged by free radicals become fragile (green arrows) and trigger senescence.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1038/s41594-022-00790-y">Ryan Barnes/Opresko Lab</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
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<h2>Why it matters</h2>
<p>Telomeres naturally shorten with age. They limit how many times a cell can divide by signaling cells to become zombies when they reach a certain length. But an excess of free radicals produced from both normal bodily processes as well as exposure to harmful chemicals like air pollution and tobacco smoke can lead to a condition called <a href="https://doi.org/10.1016/j.mad.2018.03.013">oxidative stress</a> that can accelerate telomere shortening. This can prematurely trigger senescence and contribute to age-related diseases, including <a href="https://doi.org/10.1172/jci120216">immunodeficiency</a>, <a href="https://doi.org/10.1038%2Fs41556-022-00842-x">cardiovascular disease</a>, <a href="https://doi.org/10.1038/nrg3246">metabolic disease</a> and <a href="https://doi.org/10.1016%2Fj.cell.2020.12.028">cancer</a>.</p>
<p>Our study reveals that telomeres not only serve as alarm clocks that indicate a cell divided too many times, but also as warning bells for harmful levels of oxidative stress. Age-related shortening of telomeres isn’t the only thing that triggers senescence; telomere damage is also sufficient to turn a cell into a zombie.</p>
<h2>What other research is being done</h2>
<p>Researchers are studying treatments and interventions that can protect telomeres from damage and prevent zombie cell accumulation. A number of studies in mice have found that removing zombie cells can promote healthy aging by improving <a href="https://doi.org/10.1111/acel.13296">cognitive function</a>, <a href="https://doi.org/10.1038/nature10600">muscle mass and function</a> and recovery from <a href="https://doi.org/10.1126/science.abe4832">viral infections</a>. </p>
<p>Researchers are also developing drugs called <a href="https://doi.org/10.1146/annurev-pharmtox-050120-105018">senolytics</a> that can either kill zombie cells or prevent them from developing in the first place.</p>
<h2>What’s next</h2>
<p>This study focuses on the consequences of telomere damage in actively dividing cells, like kidney and skin cells. We’re now looking at how this damage will play out in cells that don’t divide, like neurons or heart muscle cells. While researchers have shown that the telomeres of nondividing cells and tissues <a href="https://doi.org/10.1038/s41556-022-00842-x">become more dysfunctional with age</a>, it’s unclear why this happens when these telomeres should not be shortening in the first place.</p><img src="https://counter.theconversation.com/content/186445/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Patricia Opresko receives funding from the National Institutes of Health and has received funding from the Glenn Foundation for Medical Research. </span></em></p><p class="fine-print"><em><span>Ryan Barnes receives funding from:
NIA F32AG067710-01
NIEHS K99ES033771</span></em></p>The protective caps at the ends of chromosomes naturally shorten over time. Researchers found that direct damage can prematurely trigger senescence and contribute to age-related diseases like cancer.Patricia Opresko, Professor of Environmental and Occupational Health, University of PittsburghRyan Barnes, Postdoctoral Researcher in Environmental and Occupational Health, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1277282019-12-05T01:45:05Z2019-12-05T01:45:05ZTick, tock… how stress speeds up your chromosomes’ ageing clock<figure><img src="https://images.theconversation.com/files/305098/original/file-20191204-70126-7cple3.jpg?ixlib=rb-1.1.0&rect=0%2C216%2C4380%2C3244&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">At a molecular level, stresses and strains can make your body clock break into a sprint.</span> <span class="attribution"><span class="source">Lightspring/Shutterstock</span></span></figcaption></figure><p>Ageing is an inevitability for all living organisms, and although we still don’t know exactly why our bodies gradually grow ever more decrepit, we are starting to grasp how it happens.</p>
<p>Our new research, <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/ele.13426">published in Ecology Letters</a>, pinpoints factors that influence one of the most important aspects of the ageing process, at the fundamental level of our DNA. It suggests how stress can cause the biochemical body clock built into our chromosomes to tick faster.</p>
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Read more:
<a href="https://theconversation.com/the-search-to-extend-lifespan-is-gaining-ground-but-can-we-truly-reverse-the-biology-of-ageing-75127">The search to extend lifespan is gaining ground, but can we truly reverse the biology of ageing?</a>
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<p>DNA - the genetic material in our cells - does not float freely in cells’ nuclei, but is organised into clumps called chromosomes. When a cell divides and produces a replica of itself, it has to make a copy of its DNA, and because of the way this process works, a tiny portion is always lost at one end of each DNA molecule. </p>
<p>To protect vital portions of DNA from being lost in the process, the ends of chromosomes are capped with special sequences called <a href="https://www.britannica.com/science/telomere">telomeres</a>. These are gradually whittled away during successive cell divisions.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/305097/original/file-20191204-70149-nj759j.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/305097/original/file-20191204-70149-nj759j.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/305097/original/file-20191204-70149-nj759j.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=472&fit=crop&dpr=1 600w, https://images.theconversation.com/files/305097/original/file-20191204-70149-nj759j.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=472&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/305097/original/file-20191204-70149-nj759j.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=472&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/305097/original/file-20191204-70149-nj759j.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=593&fit=crop&dpr=1 754w, https://images.theconversation.com/files/305097/original/file-20191204-70149-nj759j.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=593&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/305097/original/file-20191204-70149-nj759j.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=593&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Telomeres (highlighted in white) are like molecular buffers for your chromosomes.</span>
<span class="attribution"><a class="source" href="http://science.nasa.gov/media/medialibrary/2006/03/16/22mar_telomeres_resources/caps.gif">US Dept of Energy Human Genome Program</a></span>
</figcaption>
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<p>This gradual loss of telomeres acts like a cellular clock: with each replication they get shorter, and at a certain point they become too short, forcing the cell into a programmed death process. The key question is what this process, which plays out on a cellular level, actually means for our mortality. Does the fate of individual cells really matter so much? Does the ticking telomere clock really count down the remaining time our bodies have to live?</p>
<p>Cellular ageing is just one of many components of ageing - but it’s one of the most important. Gradual deterioration of our body’s tissues, and the irreversible death of our cells, are responsible for the most conspicuous effects of ageing such as loss of physical fitness, deterioration of connective tissues leading to skin wrinkles, or neurodegenerative diseases such as Parkinson’s disease.</p>
<h2>What makes us tick?</h2>
<p>Another crucial question is: are there factors that speed up or slow down the loss of our ticking telomeres? </p>
<p>So far, our answers to this question have been incomplete. Studies have provided glimpses of possible mechanisms, suggesting that things like <a href="https://science.sciencemag.org/content/347/6220/436/tab-figures-data">infections</a> or even <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/jeb.12479">dedicating extra energy to reproduction</a> might accelerate telomere shortening and speed up cellular ageing. </p>
<p>This evidence is piecemeal, but these factors all seem to have one thing in common: they cause “physiological stress”. Broadly speaking, our cells are stressed when their biochemical processes are disrupted, either by a lack of resources or for some other reason. If cells lose too much water, for example, we might say they are in “dehydration stress”.</p>
<p>More familiar types of stress also count. Tiredness and overwork put us under chronic stress, as does feeling anxious for prolonged periods. <a href="https://www.sciencedaily.com/releases/2018/07/180712141715.htm">Lack of sleep</a> or <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763246/">emotional stress</a> can alter internal cellular pathways, including telomere functioning.</p>
<p>With this in mind, we asked ourselves one simple question. Can various types of stress experienced by an individual actually accelerate their rate of ageing?</p>
<h2>Stress and strain</h2>
<p>In our research, led by my colleague Marion Chatelain of the University of Warsaw (currently University of Innsbruck), we chose to look at this question as broadly as possible. Many studies have looked at this problem in specific species, such as mice, rats, and various fish and bird species (both wild and in the lab). We compiled the available evidence into a summary of the existing knowledge, across all vertebrate organisms studied so far.</p>
<p>The emerging picture clearly suggests that telomere loss is profoundly impacted by stress. All else being equal, stress does indeed hasten telomere loss and accelerate the internal cellular clock. </p>
<p>Importantly, the type of stress matters: by far the strongest negative impact is caused by pathogen infections, competition for resources, and intensive investment in reproduction.</p>
<p>Other stressors, such as poor diet, human disturbance or urban living, also hastened cellular ageing, although to a lesser extent.</p>
<h2>Getting radical</h2>
<p>A natural question arises: what makes stress exert such a powerful influence on cellular clocks? Is there a single mechanism, or many? Our analysis may have identified one possible candidate: “oxidative stress”. </p>
<p>When cells are stressed, this often manifests itself through an accumulation of oxidising molecules, such as <a href="https://theconversation.com/health-check-the-untrue-story-of-antioxidants-vs-free-radicals-15920">free radicals</a>. Residing at the exposed ends of our chromosomes, telomeres are perfect targets for attack by these chemically reactive molecules. </p>
<p>Our analysis suggests that, regardless of the type of stress experienced, this oxidative stress might be the actual biochemical process that links stress and telomere loss. As to whether this means that we should eat more <a href="https://www.britannica.com/science/antioxidant">antioxidants</a> to guard our telomeres, this certainly requires more research.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/health-check-the-untrue-story-of-antioxidants-vs-free-radicals-15920">Health Check: the untrue story of antioxidants vs free radicals</a>
</strong>
</em>
</p>
<hr>
<p>I know what you’re wondering: does this mean we have discovered the secret of ageing? Can we use this knowledge to slow the ageing process or stop it in its tracks? The short answer is: no. </p>
<p>Ageing is too fundamental to our biology to get rid of it completely. But our study does underline an important truth: by reducing stress, we can do our bodies a big favour. </p>
<p>In the modern world, it is hard to escape stress completely, but we can make everyday decisions to reduce it. Get enough sleep, drink enough water, eat healthily and don’t push yourself too hard. It won’t buy you eternal life, but it should keep your cells ticking along nicely.</p>
<hr>
<p><em>The author thanks his colleagues <a href="https://www.uibk.ac.at/ecology/staff/persons/chatelain.html.en">Marion Chatelain</a> and <a href="https://cent.uw.edu.pl/en/person/prof-marta-szulkin/">Marta Szulkin</a> for their contributions to this article and the research on which it is based.</em></p><img src="https://counter.theconversation.com/content/127728/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Szymek Drobniak works for the University of New South Wales and the Jagiellonian University in Poland. He receives funding from the Australian Research Council. He is also a member of the Evolutionary Knowledge for Everyone association, the European Society for Evolutionary Biology and the Society for the Study of Evolution.</span></em></p>Emerging evidence suggests that prolonged stress exposure can accelerate the ticking rate of an internal cellular clock. By doing so, stress can contribute to faster ageing and body deterioration.Szymek Drobniak, DECRA Fellow, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1180192019-07-12T12:05:55Z2019-07-12T12:05:55ZDNA testing companies offer telomere testing – but what does it tell you about aging and disease risk?<figure><img src="https://images.theconversation.com/files/279839/original/file-20190617-118526-1vzymuy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A telomere age test kit from Telomere Diagnostics Inc. and saliva
collection kit from 23andMe.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/seattle-usa-july-6-2017-new-672722578?src=n_CtwFbEEZev1k4RH8-TdA-1-59&studio=1">Anna Hoychuk/Shutterstock.com</a></span></figcaption></figure><p>Over the past few years direct-to-consumer genetic tests that extract information from DNA in your chromosomes <a href="https://www.technologyreview.com/s/610233/2017-was-the-year-consumer-dna-testing-blew-up/">have become popular</a>. Through a simple cheek swab, saliva collection or finger prick, companies offer the possibility of learning more about your family tree, ancestry, or risk of developing diseases such as Alzheimer’s or even certain cancers. More recently, <a href="https://doi.org/10.1038/embor.2011.166">some companies</a> offer tests to measure the tips of chromosomes, called telomeres, to learn more about aging.</p>
<p>But what exactly are telomeres, what are telomere tests, and what are companies claiming they can tell you? Age based on your birthday versus your “telomere age”?</p>
<p>Telomeres play a big role in keeping our chromosomes and bodies healthy even though they make up only a tiny fraction of our total DNA. The Greek origins of the word telomere describes where to find them. “Telo” means “end” while “mere” means “part.” Telomeres cap both ends of all 46 chromosomes in each cell, and protect chromosomes from losing genetic material. They are often compared to the plastic tips at the ends of shoelaces that prevent fraying.</p>
<p><a href="http://www.opreskolab.com">We are</a> <a href="https://www.publichealth.pitt.edu/home/directory/patricia-opresko">molecular</a> <a href="https://www.jefferson.edu/university/jmc/departments/biochemistry/faculty-staff/faculty/elise.html">biologists</a> studying how chemicals, agents from the environment and metabolism damage telomeres and affect their lengths and function, and how damaged telomeres affect the health of our cells and genome. The idea of offering telomere length as part of a genetic test is intriguing since telomeres protect our genetic material. But equating telomere length with something as complex as aging struck us as tricky and overly simplistic. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/279837/original/file-20190617-118539-130f0e2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/279837/original/file-20190617-118539-130f0e2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/279837/original/file-20190617-118539-130f0e2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=300&fit=crop&dpr=1 600w, https://images.theconversation.com/files/279837/original/file-20190617-118539-130f0e2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=300&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/279837/original/file-20190617-118539-130f0e2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=300&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/279837/original/file-20190617-118539-130f0e2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=377&fit=crop&dpr=1 754w, https://images.theconversation.com/files/279837/original/file-20190617-118539-130f0e2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=377&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/279837/original/file-20190617-118539-130f0e2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=377&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Telomeres get shorter with each round of cell division.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/telomere-shortening-each-round-cell-division-708788029?studio=1">Kateryna Kon/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Link between telomere length and human diseases</h2>
<p>Telomeres are important for human health and despite their protective function, they are not indestructible. Telomeres shorten every time a cell divides and shorten progressively as we age.</p>
<p>When telomeres become too short or lost, the chromosome tips are left unprotected and become sticky. This can cause chromosomes to fuse. To prevent further chromosome shortening and fusions, the cells enter senescence, a state in which they can no longer divide. Although they lose the ability to rejuvenate tissues, senescent cells can still promote inflammation and secrete factors that favor growth of nearby pre-cancerous or cancerous cells.</p>
<p>Unfortunately, our lifestyle can actually accelerate the shortening. Environmental exposures such as sunlight, air pollution, cigarette smoke and even inflammation or poor diet can damage cell components, including DNA. They do this by generating unstable oxygen molecules, or free radicals. Telomeres are particularly susceptible to damage by free radicals. </p>
<p>In collaboration with chemist <a href="https://www.cmu.edu/bio/people/faculty/bruchez.html">Marcel Bruchez</a>, we developed a new tool that damages only the telomeres. Using this tool we discovered that oxidative damage to telomeres is sufficient to not only accelerate their shortening but also to cause <a href="https://doi.org/10.1016/j.molcel.2019.04.024">telomere loss</a>. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/9gxogiUvVkk?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Our study shows oxidative damage to telomeres directly causes shortening.</span></figcaption>
</figure>
<p>In previous laboratory experiments, scientists found that eliminating senescent cells from mice led to the <a href="https://doi.org/10.1038/nature10600">delay or prevention of diseases and conditions</a> associated with aging including heart disease, diabetes, osteoporosis and lung fibrosis. This has led to the <a href="https://doi.org/10.1111/jgs.14969">pursuit of new drugs called senolytics</a> that could eliminate senescent cells in humans.</p>
<h2>Is longer better?</h2>
<p>Since short telomeres cause cells to senesce, this makes them interesting targets for healthy, disease-free aging. Also, since telomeres shorten with age, regardless of exposure to toxins this led to the notion that telomere length may provide information about a person’s “true” biological age. </p>
<p>Commercial tests typically measure telomere lengths or amounts of telomeric DNA in a blood sample. Companies compare your telomeres to telomeres from people of similar age to try to determine the biological age of your blood cells. </p>
<p>However, just as individuals of the same age vary in height and weight, so do telomeres. If a child falls in the 40th percentile for height, this means compared to 100 girls her age she is taller than 40. For this reason, charts similar to growth charts for children have been generated for telomeres. </p>
<p>Individuals with telomere lengths below the first percentile are at risk for developing specific diseases including anemia, immunodeficiency and pulmonary fibrosis, <a href="https://doi.org/10.1016/j.gde.2015.06.004">likely due to a gene mutation that impairs telomere maintenance</a> </p>
<p>At the other extreme, individuals with <a href="https://doi.org/10.1016/j.gde.2015.06.004">gene mutations that lead to very long telomeres</a> above the 99th percentile are at greater risk for developing inherited forms of melanoma and brain cancers. Longer telomeres allow a cell to divide more times, and with every division there is a chance that an error during genome duplication produces a mutation that promotes cancer. In a way, telomeres follow the Goldilock’ principle. Telomeres that are too short or too long are not optimal.</p>
<h2>Can telomere length predict health outcomes?</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/279847/original/file-20190617-118535-1tn0rfh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/279847/original/file-20190617-118535-1tn0rfh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/279847/original/file-20190617-118535-1tn0rfh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/279847/original/file-20190617-118535-1tn0rfh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/279847/original/file-20190617-118535-1tn0rfh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/279847/original/file-20190617-118535-1tn0rfh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/279847/original/file-20190617-118535-1tn0rfh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Exercise and a healthy diet are associated with longer telomeres.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/senior-couple-on-cycle-ride-countryside-180842051?src=yfmTSGPVrotvd6dZz9Vo8Q-1-46&studio=1">Monkey Business Images/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>But what about telomere lengths in between the extremes? Large studies involving hundreds to thousands of participants show general associations of shorter telomeres with <a href="https://doi.org/10.1161/CIRCGENETICS.113.000485">increased risk for some diseases of aging, including heart disease</a>, whereas <a href="https://doi.org/10.1001/jamaoncol.2016.5945">longer telomeres are associated with increased risk for some types of cancers</a>. </p>
<p>But translating these population studies to predictions about individual life spans and health is difficult. For example, as a group, men are taller than women, but that does not mean all men are taller than women. Similarly, some people with shorter telomeres do not develop heart disease in these population studies. More studies are needed to fully understand what an individual’s telomere length means for their health and aging. </p>
<p>While large population studies show a healthy diet is associated with longer telomeres, published reports about specific supplements <a href="https://doi.org/10.1016/j.metabol.2015.11.004">that claim to support telomere health are lacking.</a></p>
<p>If such a product could extend telomeres, would it be safe? Or would it increase one’s risk for developing cancer due to long telomeres? Can protecting telomeres or slowing their shortening promote disease-free aging? We do not have the answers to these questions yet.</p>
<p>Given the uncertainty and risk of wrong interpretation, should you have your telomeres measured? Maybe, if the results motivate healthy lifestyle changes. For now, a surer bet for healthy aging would be to spend the money on exercise programs and nutritious foods instead. </p>
<p>[ <em><a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=expertise">Expertise in your inbox. Sign up for The Conversation’s newsletter and get a digest of academic takes on today’s news, every day.</a></em> ]</p><img src="https://counter.theconversation.com/content/118019/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Patricia Opresko receives funding from the National Institutes of Health. </span></em></p><p class="fine-print"><em><span>Elise Fouquerel receives funding from National Institutes of Health. </span></em></p>Genetic testing companies are offering tests that analyze the ends of your chromosomes – telomeres – to gauge your health and your real age. But is there scientific evidence to support such tests?Patricia Opresko, Professor of Environmental and Occupational Health, University of PittsburghElise Fouquerel, Assistant Professor of Biochemistry and Molecular Biology, Thomas Jefferson UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1118122019-04-11T18:03:38Z2019-04-11T18:03:38ZDoes a year in space make you older or younger?<figure><img src="https://images.theconversation.com/files/266378/original/file-20190328-139374-iyqwl2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Are space twin Scott and Earth twin Mark no longer identical?</span> <span class="attribution"><a class="source" href="https://www.nasa.gov/content/scott-kelly-and-mark-kelly-at-the-johnson-space-center2">Robert Markowitz/NASA</a></span></figcaption></figure><p>Daily life aboard the International Space Station moves fast. Really fast. Traveling at approximately 17,000 miles per hour, 300 miles above the Earth, astronauts watch 16 sunrises and sunsets every “day” while floating around in a box with a handful of people they depend on for survival.</p>
<p>One need look no further than Hollywood blockbusters like “<a href="https://www.imdb.com/title/tt3659388/">The Martian</a>,” “<a href="https://www.imdb.com/title/tt1454468/?ref_=fn_al_tt_1">Gravity</a>” and “<a href="https://www.imdb.com/title/tt0816692/?ref_=fn_al_tt_1">Interstellar</a>” for futuristic visions of life beyond Earth as we venture longer and deeper into outer space. But what about the human body’s response to real-life spaceflight – what are the health effects? Will space travelers age at different rates than those of us on Earth? Just how adaptable to the space environment are we? </p>
<p>Certainly these are concerns for NASA. How space travel and long-duration missions might change the human body, and whether those changes are permanent or reversible once astronauts return to Earth, is largely unknown. The opportunity to explore these intriguing questions arose with identical twin astronauts Scott and Mark Kelly. </p>
<p>In November of 2012, NASA selected astronaut Scott Kelly for its first one-year mission. At a press conference not long thereafter, it was Scott who hinted that that this mission might provide the chance to compare the impact of space living on his body with his Earth-dwelling identical twin brother, Mark Kelly, who had also been an astronaut and former Navy test pilot. Remarkably, the Kelly twins were individuals of similar “nature (genetics) and nurture (environment),” and so the perfect space experiment was conceived – featuring “space twin and Earth twin” as the stars. Scott would spend a year in space aboard the International Space Station, while his identical twin brother, Mark, would remain on Earth.</p>
<p>The <a href="https://www.nasa.gov/twins-study">NASA TWINS Study</a> represents the most comprehensive view of the human body’s response to space flight ever conducted. Results will guide future studies and personalized approaches for evaluating health effects of individual astronauts for years to come.</p>
<p><a href="http://csu-cvmbs.colostate.edu/academics/erhs/Pages/susan-bailey.aspx">As a cancer biologist</a> at Colorado State University I study the impact of radiation exposure on human cells. As part of the TWINS Study, I was particularly interested in evaluating how the ends of the chromosomes, called telomeres, were altered by a year in space.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/266411/original/file-20190328-139356-g4thsi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/266411/original/file-20190328-139356-g4thsi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=443&fit=crop&dpr=1 600w, https://images.theconversation.com/files/266411/original/file-20190328-139356-g4thsi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=443&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/266411/original/file-20190328-139356-g4thsi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=443&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/266411/original/file-20190328-139356-g4thsi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=556&fit=crop&dpr=1 754w, https://images.theconversation.com/files/266411/original/file-20190328-139356-g4thsi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=556&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/266411/original/file-20190328-139356-g4thsi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=556&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">One day before astronaut Scott Kelly reaches the six-month mark in space, he talks live from onboard the ISS with John Hughs, left, his twin brother Mark Kelly and Astronaut Terry Virts, right.</span>
<span class="attribution"><a class="source" href="https://www.nasa.gov/image-feature/halfway-through-a-year-in-space">NASA/Bill Ingalls</a></span>
</figcaption>
</figure>
<h2>Teasing apart health effects of space living</h2>
<p>NASA put out a call and selected 10 peer-reviewed investigations from around the country for the TWINS Study. Studies included molecular, physiological and behavioral measures, and for the first time ever in astronauts, “omics”-based studies. Some teams evaluated the impact of space on the genome – the entire complement of DNA in a cell (genomics). Other teams examined which genes were turned on and producing a molecule called mRNA (transcriptomics). Some studies focused on how chemical modifications – which do not alter the DNA code – affected the regulation of the genes (epigenomics). Some researchers explored the proteins produced in the cells (proteomics), whereas others scrutinized the products of metabolism (metabolomics).</p>
<p>There were also studies examining how the space environment might alter the microbiome – the collection of bacteria, viruses and fungi that live in and on our bodies. One investigation examined the immune response to the flu vaccine. Other teams searched Scott’s biological samples for biomarkers of atherosclerosis and upward fluid shifts in the body due to microgravity, which can affect vision and cause headaches. Cognitive performance was also evaluated using computer-run cognition tests specifically designed for astronauts. </p>
<p>More than 300 biological samples – stool, urine and blood – were collected from the twins at multiple times before, during and after the one year mission. </p>
<p>The Kelly twins are without a doubt one of the most profiled pairs – on or off our planet. They are also one of the most interviewed. One question often asked is whether Scott will return from space younger than Mark – a situation reminiscent of “Interstellar” or Einstein’s so-called “<a href="https://www.scientificamerican.com/article/how-does-relativity-theor/">Twin Paradox</a>.” However, because the ISS is not traveling anywhere near the speed of light relative to us, time dilation – or the slowing of time due to motion – is very minimal. So any age difference between the brothers would only be a few milliseconds.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/266408/original/file-20190328-139361-2ycan1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/266408/original/file-20190328-139361-2ycan1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/266408/original/file-20190328-139361-2ycan1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=735&fit=crop&dpr=1 600w, https://images.theconversation.com/files/266408/original/file-20190328-139361-2ycan1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=735&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/266408/original/file-20190328-139361-2ycan1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=735&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/266408/original/file-20190328-139361-2ycan1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=924&fit=crop&dpr=1 754w, https://images.theconversation.com/files/266408/original/file-20190328-139361-2ycan1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=924&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/266408/original/file-20190328-139361-2ycan1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=924&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Telomeres are the protective sections of DNA at the tip of the chromosomes. As people age the telomeres get shorter.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/telomere-vector-illustration-educational-medical-scheme-1144289204">VectorMine/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Even so, the question of spaceflight-associated aging and the accompanying risk of developing age-related diseases like dementia, cardiovascular disease and cancer – during or after a mission – is an important one, and one that we aimed to address directly with our study of telomere length. </p>
<p>Telomeres are the ends of chromosomes that protect them from damage and from “fraying” – much like the end of a shoestring. Telomeres are critical for maintaining chromosome and genome stability. However, telomeres naturally shorten as our cells divide, and so also as we age. The rate at which telomeres shorten over time is influenced by many factors, including oxidative stress and inflammation, nutrition, physical activity, psychological stresses and environmental exposures like air pollution, UV rays and ionizing radiation. Thus, telomere length reflects an individual’s genetics, experiences and exposures, and so are informative indicators of general health and aging. </p>
<h2>Telomeres and aging</h2>
<p>Our study proposed that the unique stresses and out-of-this-world exposures the astronauts experience during spaceflight – things like isolation, microgravity, high carbon dioxide levels and galactic cosmic rays – would accelerate telomere shortening and aging. To test this, we evaluated telomere length in blood samples received from both twins before, during and after the one year mission. </p>
<p>Scott and Mark started the study with relatively similar telomere lengths, which is consistent with a strong genetic component. Also as expected, the length of Earth-bound Mark’s telomeres was relatively stable over the course of the study. But much to our surprise, <a href="https://science.sciencemag.org/cgi/doi/10.1126/science.aau8650">Scott’s telomeres were significantly longer</a> at every time point and in every sample tested during spaceflight. That was exactly the opposite of what we expected. </p>
<p>Furthermore, upon Scott’s return to Earth, telomere length shortened rapidly, then stabilized during the following months to near pre-flight averages. However, from the perspective of aging and risk of disease, he had many more short telomeres after spaceflight than he did before. Our challenge now is to figure out how and why such spaceflight specific shifts in telomere length dynamics are occurring. </p>
<p>Our findings will have relevance to earthlings as well, since we all grow old and develop age-related conditions. These TWINS Study results may provide new clues into the processes involved, and thereby improve our understanding of what we might do to avoid them or extend health span.</p>
<p>The long-term health effects of long duration spaceflight are yet to be determined, but the TWINS Study represents a landmark step in humankind’s journey to the moon, Mars and beyond…and to making science fiction science fact. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/Nus-cMzhbug?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Susan Bailey describes the telomere study.</span></figcaption>
</figure><img src="https://counter.theconversation.com/content/111812/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Susan Bailey owns shares in KromaTid, Inc. </span></em></p>Before sending humans to Mars or the moon, scientists need to understand what long-term space living does to the human body. Now results are coming in from the Kelly brothers in the TWINS Study,Susan Bailey, Professor of Radiation Cancer Biology and Oncology, Colorado State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/992692018-07-16T10:40:07Z2018-07-16T10:40:07ZHow summer and diet damage your DNA, and what you can do<figure><img src="https://images.theconversation.com/files/227013/original/file-20180710-70042-k19evn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Bright sun and fatty foods are a bad recipe for your DNA.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/tropical-beach-young-woman-eating-bacon-79975609?src=nygk_hV_YRRiGe-FmHTS8A-1-15">By Tish1/shutterstock.com</a></span></figcaption></figure><p>Today, your body will accumulate <a href="https://www.ncbi.nlm.nih.gov/pubmed/28187286">quadrillions of new injuries in your DNA</a>. The constant onslaught of many forms of damage, some of which permanently mutates your genes, could initiate cancer and prove fatal. Yet all is not doomed: The lives we lead determine how well our cells can handle this daily molecular erosion.</p>
<p>Certain cells are particularly at risk. Your skin, for instance, is constantly being bombarded by high-energy UV light that wreaks havoc on your DNA. This UV light should not be taken lightly — <a href="https://www.aad.org/media/stats/conditions/skin-cancer">1 in 5 Americans develops skin cancer</a> in their lifetime, more than any other cancer. So as you’re hitting the beach with sugary margaritas in hand, remember that deadly <a href="https://www.aad.org/media/stats/conditions/skin-cancer">skin cancer rates are at record-highs</a>, as are cancers <a href="https://www.nature.com/scitable/topicpage/dna-replication-and-causes-of-mutation-409">associated with obesity</a>. </p>
<p>I am a medical student in <a href="https://www.opreskolab.com">Dr. Patricia Opresko’s lab</a> at the University of Pittsburgh, which stands at the intersection of two Nobel Prize-winning disciplines: DNA repair and telomeres. Telomeres are protective regions at the ends of our chromosomes that hold the DNA together like the plastic cap on your shoelace. Her lab’s work is revealing the molecular machinery that repairs your telomeres after <a href="https://doi.org/10.1038/ncomms9214">UV</a> and <a href="https://www.ncbi.nlm.nih.gov/pubmed/28981887">metabolic</a> (related to energy extraction from food) damage, and the many ways it can go awry. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/227009/original/file-20180710-70063-w6mmdf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/227009/original/file-20180710-70063-w6mmdf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=342&fit=crop&dpr=1 600w, https://images.theconversation.com/files/227009/original/file-20180710-70063-w6mmdf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=342&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/227009/original/file-20180710-70063-w6mmdf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=342&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/227009/original/file-20180710-70063-w6mmdf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=429&fit=crop&dpr=1 754w, https://images.theconversation.com/files/227009/original/file-20180710-70063-w6mmdf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=429&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/227009/original/file-20180710-70063-w6mmdf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=429&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Telomeres are protective caps on the end of chromosomes.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/telomeres-protective-caps-on-end-chromosomes-710795275?src=gVTu341uTq45n717aUCdLQ-1-0">By Fancy Tapis/shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Telomeres: Where chromosomes end and our research begins</h2>
<p>In the minute you’ve been reading, hundreds of trillions of new lesions have occurred in your DNA. Fortunately, a special class of proteins is vigilantly detecting and repairing these errors.</p>
<p>Repair is particularly important in telomeres. </p>
<p>The telomere is no small thing, at least not figuratively: Their length is correlated with many symptoms of aging. Human studies have shown that people with shorter telomeres suffer <a href="https://doi.org/10.1093/gerona/glq180">worsened immunity and heart disease along with greater mortality</a>. With every year, your telomeres get shorter, some cells stop replicating, and these symptoms worsen. We do not yet know whether telomeres are the secret to aging. What we do know is that UV and metabolic damage, which further shorten telomeres, can trigger cancer and aging; when you break the plastic cap, you unravel the whole shoelace.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/227011/original/file-20180710-70048-gd9ii2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/227011/original/file-20180710-70048-gd9ii2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/227011/original/file-20180710-70048-gd9ii2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/227011/original/file-20180710-70048-gd9ii2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/227011/original/file-20180710-70048-gd9ii2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/227011/original/file-20180710-70048-gd9ii2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/227011/original/file-20180710-70048-gd9ii2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A nasty sunburn can induce DNA damage in skin cells leading to skin cancer.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sunburn-beach-sun-light-on-shoulder-457727173?src=5lZafxTg3VeIOfhXVTldxw-1-3">By Jingjits Photography/shutterstock.com</a></span>
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<p>Bathing our skin in UV light causes an onslaught of damage. In fact, regular <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471149/">skin cells from older adults have about as many mutations as cancer cells</a>. At best, the sun’s dangerous rays can cause the skin cells to commit suicide and flake off. At worst, those cells remain and become cancerous.</p>
<p>One such “molecular sunburn” is called a photoproduct, which forms when the energy from UV light causes two adjacent units of your DNA to stick together, potentially interfering with its normal function. <a href="https://www.ncbi.nlm.nih.gov/pubmed/19812404">Ten thousand</a> photoproducts occur in every skin cell every day due to sun exposure. </p>
<h2>You (and your telomeres) are what you eat</h2>
<p>Telomeres are especially prone to such damage. And although telomeres don’t contain valuable body-building instructions like genes, when photoproducts damage our telomeres, a cell can turn on a special protein called telomerase which makes the telomeres longer. This might sound like a way to stay forever young. After all, aren’t short telomeres the culprit of aging? But in extending its telomeres, the cell no longer has a limit to how many times it can replicate. This explains why over <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384178/">85 percent of all cancers exhibit extended telomeres</a>. It seems that while longer telomeres are the key to our immortality, under the wrong circumstances, they can also be our downfall. When we fail to use UV protective sunscreen to safeguard our telomeres, we are, quite literally, flying too close to the sun.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/227015/original/file-20180710-70057-67h0b1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/227015/original/file-20180710-70057-67h0b1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=434&fit=crop&dpr=1 600w, https://images.theconversation.com/files/227015/original/file-20180710-70057-67h0b1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=434&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/227015/original/file-20180710-70057-67h0b1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=434&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/227015/original/file-20180710-70057-67h0b1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=545&fit=crop&dpr=1 754w, https://images.theconversation.com/files/227015/original/file-20180710-70057-67h0b1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=545&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/227015/original/file-20180710-70057-67h0b1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=545&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Overeating causes the production of more DNA damaging molecules that can harm telomeres, in some cases causing cancer.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-three-obese-fat-men-on-51152629">By Tish1/shutterstock.com</a></span>
</figcaption>
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<p>Your metabolism, which breaks down food to extract energy, generates high-energy particles called free radicals that, like UV light, can distort the units in your DNA. This, in turn, wears away at your telomeres. Such metabolic damage accumulates over a lifetime of eating. Scientists believe this is why older, overweight adults, who have spent many years metabolizing more food than average, have a far greater risk of <a href="https://doi.org/10.1111/j.1474-9726.2010.00583.x">telomere shortening</a> and <a href="https://www.cdc.gov/media/releases/2017/p1003-vs-cancer-obesity.html">cancer</a>. Moreover, it seems diets rich in <a href="https://doi.org/10.1002/ijc.24105">antioxidants, found in fruits, vegetables, nuts and legumes, which counter that metabolic damage, actually protect telomeres as well</a>. </p>
<h2>Lengthening our telomeres and our lives</h2>
<p>While our telomere length once seemed pre-determined by our genes, the more medical researchers learn, the more we realize the impact of our lifestyles. <a href="https://doi.org/10.1097/MCO.0b013e32834121b1">Smoking, UV-light exposure, obesity, lack of exercise, stress and poor diet can all diminish our telomeres</a>, squandering our molecular fountain of youth. </p>
<p>In Dr. Patricia Opresko’s lab, we are investigating how telomere repair keeps up with the damage wrought by our daily lives, as well as the dire consequences when it no longer can. The hope is that by better understanding the mechanisms of cancer formation, we can design better therapies. Yet our findings are important not only for treating cancer, but also for preventing it.</p>
<p>My grandfather lost his battle against an aggressive form of skin cancer just weeks before my bar mitzvah. My grandmother, who valued education above all else, died of cancer days prior to my high school graduation. Their untimely loss inspired me to take up research in the very center where they received their care. Every cancer cell I study, and every hallway I walk, I am reminded of my grandparents and the countless other like them that could benefit from our research. </p>
<p>As King Henry VIII noted, time is the only invincible opponent. My grandparents are among the billions who succumbed to the onslaught of time. In studying telomeres, many are searching for an elusive fountain of youth that can reverse aging and overcome death. Yet the answers that we uncover are far less fanciful. It is not our telomeres that shorten our lifespans but our lives that shorten our telomeres. As many as half of medical deaths in the United States <a href="https://www.cdc.gov/media/releases/2014/p0501-preventable-deaths.html">are preventable</a>. Small choices as simple as using <a href="https://doi.org/10.1001/jamadermatol.2015.1253">UV-A and UV-B protective sunscreen</a>, eating smarter and exercising regularly can go a long way in empowering us to take command of our health.</p>
<p>We still have much to learn before we can use the secrets of our telomeres to surpass the limitations of our genetic makeup. But there are countless steps you can take today to protect your telomeres from the sun and from yourself. Research barters in knowledge, but it is action, inspired by knowledge, which can keep families like mine together for longer.</p><img src="https://counter.theconversation.com/content/99269/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adam Barsouk does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Scientists have long thought that regions of DNA called telomeres control how long you live. We are now learning that it is your diet and lifestyle that shape your telomeres, not the other way around.Adam Barsouk, Research Assistant, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/955912018-04-25T17:09:15Z2018-04-25T17:09:15ZEnd of ageing and cancer? Scientists unveil structure of the ‘immortality’ enzyme telomerase<figure><img src="https://images.theconversation.com/files/216380/original/file-20180425-175044-pm9x2m.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Telomeres on a chromosome.</span> <span class="attribution"><span class="source">AJC1/Flickr</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>Making a drug is like trying to pick a lock at the molecular level. There are two ways in which you can proceed. You can try thousands of different keys at random, hopefully finding one that fits. The pharmaceutical industry does this all the time – sometimes screening hundreds of thousands of compounds to see if they interact with a certain enzyme or protein. But unfortunately it’s not always efficient – there are <a href="http://www3.uah.es/farmamol/Public/PDF_files/screening.pdf">more drug molecule shapes</a> than seconds have passed since the beginning of the universe.</p>
<p>Alternatively, like a safe cracker, you can x-ray the lock you want to open and work out the probable shape of the key from the pictures you get. This is much more effective for discovering drugs, as you can use computer models to identify promising compounds before researchers go into the lab to find the best one. Now a study, <a href="http://nature.com/articles/doi:10.1038/s41586-018-0062-x">published in Nature</a>, presents detailed images of a crucial anti-ageing enzyme known as telomerase – raising hopes that we can soon slow ageing and cure cancer.</p>
<p>Every organism packages its DNA into chromosomes. In simple bacteria like E. coli this is a single small circle. More complex organisms have far more DNA and multiple linear chromosomes (22 pairs plus sex chromosomes). These probably appeared because they <a href="https://academic.oup.com/gbe/article/5/6/1142/617665">provided an evolutionary advantage</a>, but they also come with a downside. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/216252/original/file-20180425-175054-8dgqfa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/216252/original/file-20180425-175054-8dgqfa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/216252/original/file-20180425-175054-8dgqfa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/216252/original/file-20180425-175054-8dgqfa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/216252/original/file-20180425-175054-8dgqfa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/216252/original/file-20180425-175054-8dgqfa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/216252/original/file-20180425-175054-8dgqfa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">We may all soon live to be centenarians.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/portrait-hundred-years-old-woman-centenarian-1022974105?src=0iBzRDx-LwAG4CGu_doeWg-1-2">Dan Negureanu/Shutterstcock</a></span>
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<p>At the end of each chromosome is a protective cap called a <a href="https://en.wikipedia.org/wiki/Telomere">telomere</a> . However, most human cells can’t copy them – meaning that every time they divide, their telomeres become shorter. When telomeres become too short, the cell enters a toxic state called “senescence”. If these senescent cells are not cleared by the immune system, they begin to compromise the function of the tissues in which they reside. For millennia, humans have perceived this gradual compromise in tissue function over time without understanding what caused it. <a href="https://theconversation.com/the-secret-to-staying-young-scientists-boost-lifespan-of-mice-by-deleting-defective-cells-54068">We simply called it ageing</a>. </p>
<p>Enter telomerase, a specialised telomere repair enzyme in two parts – able to add DNA to the chromosome tips. The first part is a protein called TERT that does the copying. The second component is called TR, a small piece of <a href="https://theconversation.com/explainer-what-is-rna-15169">RNA</a> which acts as a template. Together, these form telomerase, which trundles up and down on the ends of chromosomes, copying the template. At the bottom, a human telomere is roughly 3,000 copies of the DNA sequence “TTAGGG” – laid down and maintained by telomerase. But sadly, production of TERT is repressed in human tissues with the exception of sperm, eggs and some immune cells. </p>
<h2>Ageing versus cancer</h2>
<p>Organisms regulate their telomere maintenance in this way because they are walking a biological tightrope. On the one hand, they need to replace the cells they lose in the course of their ordinary daily lives by cell division. However, any cell with an unlimited capacity to divide is the seed of a tumour. And it turns out that the majority of human cancers have active telomerase and shorter telomeres than the cells surrounding them. </p>
<p>This indicates that the cell from which they came divided as normal but then picked up a mutation which turned TERT back on. Cancer and ageing are flip sides of the same coin and telomerase, by and large, is doing the flipping. Inhibit telomerase, and you have a treatment for cancer, activate it and you prevent senescence. That, at least, is the theory.</p>
<p>The researchers behind the new study were not just able to obtain the structure of a proportion of the enzyme, but of the entire molecule as it was working. This was a tour de force involving the use of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409662/">cryo-electron microscopy</a> – a technique using a beam of electrons (rather than light) to take thousands of detailed images of individual molecules from different angles and combine them computationally.</p>
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<p>Prior to the development of this method, for which scientists <a href="https://theconversation.com/trio-behind-method-to-visualise-the-molecules-of-life-wins-2017-nobel-prize-in-chemistry-85209">won the Nobel Prize last year</a>, it was necessary to <a href="https://en.wikipedia.org/wiki/Protein_crystallization">crystallise proteins</a> to image them. This typically requires thousands of attempts and many years of trying, if it works at all. </p>
<h2>Elixir of youth?</h2>
<p>TERT itself is a large molecule and although it has shown to lengthen lifespan when introduced into <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494070/">normal mice using gene therapy</a> this is technically challenging and fraught with difficulties. Drugs that can turn on the enzyme that produces it are far better, easier to deliver and cheaper to make. </p>
<p>We already know of a few compounds to inhibit and activate telomerase – discovered through the cumbersome process of randomly screening for drugs. Sadly, they are not very efficient.</p>
<p>Some of the most provocative studies involve the compound TA-65 (Cycloastragenol) – a natural product which lengthens telomeres experimentally and has been claimed to show benefit in early <a href="https://academic.oup.com/gbe/article/5/6/1142/617665">stage macular degeneration</a> (vision loss). As a result, TA65 has been sold over the internet and has prompted at least one (subsequently <a href="http://www.ta65lawsuit.com/">dismissed</a>) lawsuit over claims that it <a href="https://www.nature.com/news/lawsuit-challenges-anti-ageing-claims-1.11090">caused cancer in a user</a>. This sad story illustrates an important public health message best summarised simply as “don’t try this at home, folks”. </p>
<p>The telomerase inhibitors we know of so far, however, have genuine clinical benefit in various <a href="https://www.ncbi.nlm.nih.gov/pubmed/28218725">cancers</a>, particularly in combination with other drugs. However, the doses required are relatively high. </p>
<p>The new study is extremely promising because, by knowing the structure of telomerase, we can use computer models to identify the most promising activators and inhibitors and then test them to find which ones are most effective. This is a much quicker process than randomly trying different molecules to see if they work.</p>
<p>So how far could could we go? In terms of cancer, it is hard to tell. The body can easily become resistant to cancer drugs, including telomerase inhibitors. Prospects for slowing ageing where there is not cancer are somewhat easier to estimate. In mice, deleting senescent cells or <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494070/">dosing with telomerase</a> (gene therapy) both give increases in lifespan of the order of 20% – despite being inefficient techniques. It may be that at some point <a href="https://theconversation.com/compound-found-in-berries-and-red-wine-can-rejuvenate-cells-suggests-new-study-86945">other ageing mechanisms</a>, such as the accumulation of damaged proteins, start to come into play.</p>
<p>But if we did manage to stop the kind of ageing caused by senescent cells using telomerase activation, we could start devoting all our efforts into tackling these additional ageing processes. There’s every reason to be optimistic that we may soon live much longer, healthier lives than we do today.</p><img src="https://counter.theconversation.com/content/95591/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Richard Faragher does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Detailed images of the anti-ageing enzyme telomerase are a drug designer’s dreamRichard Faragher, Professor of Biogerontology, University of BrightonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/893572018-01-22T11:28:19Z2018-01-22T11:28:19ZWhen a mom feels depressed, her baby’s cells might feel it too<figure><img src="https://images.theconversation.com/files/202172/original/file-20180116-53307-epjvhk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">At just 18 months old, young children can show biological evidence of added stress.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/little-boy-kid-blue-jeans-crying-297378290?src=G6FVz2rzEYQtdFqhHufgMg-1-28">Coy_Creek/shutterstock.com</a></span></figcaption></figure><p>An estimated <a href="https://www.cdc.gov/reproductivehealth/depression/index.htm">1 in 9 women</a> experience symptoms of postpartum depression. These symptoms – including mood swings, fatigue and reduced interest in activities – can make it difficult for mothers to bond with their newborns.</p>
<p>Early relationships between mothers and their infants can <a href="https://doi.org/10.1001/jama.2009.754">influence health</a> across the lifespan, for better or worse. For example, adults who report more household dysfunction and abuse during their childhood are <a href="https://doi.org/10.1016/S0749-3797(98)00017-8">more likely to suffer disease as adults</a>. Those with healthy and supportive relationships during early life <a href="https://www.ncbi.nlm.nih.gov/pubmed/11931522">are better at handling stress and regulating their emotions</a>.</p>
<p>However, scientists do not completely understand how these environments get “under the skin” to <a href="http://doi.org/10.1126/scisignal.2003580">shape health</a>. Our <a href="https://doi.org/10.1016/j.psyneuen.2017.11.008">2017 paper</a> showed a possible link between increasing depression symptoms in mothers and cellular damage in their infants.</p>
<h2>Telomeres and health</h2>
<p>How does stress affect our cells? One area of burgeoning research focuses on <a href="https://www.nature.com/articles/490169a">telomeres</a>. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/202463/original/file-20180118-158513-1l0h5mr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/202463/original/file-20180118-158513-1l0h5mr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/202463/original/file-20180118-158513-1l0h5mr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=639&fit=crop&dpr=1 600w, https://images.theconversation.com/files/202463/original/file-20180118-158513-1l0h5mr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=639&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/202463/original/file-20180118-158513-1l0h5mr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=639&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/202463/original/file-20180118-158513-1l0h5mr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=803&fit=crop&dpr=1 754w, https://images.theconversation.com/files/202463/original/file-20180118-158513-1l0h5mr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=803&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/202463/original/file-20180118-158513-1l0h5mr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=803&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The 46 human chromosomes are shown in blue, with the telomeres appearing as white pinpoints.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/nihgov/24190672366/">NIH Image Gallery</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>Telomeres are caps at the end of our DNA that protect chromosomes. They’re analogous to the plastic tips at the end of shoelaces that keep laces from unraveling. In essence, these plastic caps keep laces functional. The same can be said of your telomeres.</p>
<p>Since the length of telomeres is affected by our genetics and age, they’re sometimes thought of as part of a “biological clock” that reflects the age of our cells. As telomeres shorten over time, people are more likely to experience a host of <a href="https://www.nature.com/articles/490169a">negative health outcomes</a>, such as cardiovascular disease, dementia, diabetes, cancer, obesity and <a href="https://doi.org/10.1093/jnci/djv074">even death</a>.</p>
<p>Interestingly, telomeres can degrade more quickly when a person suffers from <a href="https://doi.org/10.1111/j.1467-8721.2009.01596.x">psychological stress</a>. When we experience stress, our bodies release a hormone called cortisol, which influences our emotional responses as well as our energy metabolism, learning and memory. This may be one <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557830/">mechanism</a> that connects psychological stress to telomere length and ultimately physical health. Cells that are exposed to cortisol have shorter telomeres and <a href="https://doi.org/10.1016/j.bbi.2007.12.004">less telomerase</a>, which is the enzyme responsible for maintaining the ends of telomeres. </p>
<p>This process may explain how psychological stress is converted to biological “wear and tear.” Indeed, <a href="https://www.nature.com/articles/mp2014119">adolescents with depressed mothers</a> have heightened cortisol stress responses and shorter telomeres than their peers, even when the adolescents themselves are not depressed.</p>
<h2>Our study</h2>
<p>We examined whether increasing maternal depressive symptoms affected infant stress and later cell health. </p>
<p>Infancy is a sensitive period, when individuals are strongly influenced by their environment. One way to study how early stress may influence health is to look at how infants respond to their parents’ stress. Studies suggest that infants exposed to maternal depression may be <a href="https://doi.org/10.1097/CHI.0b013e3181b21651">less likely to engage socially and experience more negative emotion</a>.</p>
<p>For our study we recruited 48 mothers with 12-week-old infants and followed these families until the infants were 18 months old. At 6 and 12 months of age, the infants were brought to the lab to engage in mildly stressful tasks. For example, in the “still face experiment,” mothers alternated between playing with their infant and not reacting to their infant’s bids for attention. This can <a href="https://www.washingtonpost.com/blogs/she-the-people/wp/2013/09/16/affects-of-child-abuse-can-last-a-lifetime-watch-the-still-face-experiment-to-see-why/">elicit stress</a> in infants, as they rely on their caregivers to not only feed them, but to also soothe their emotions.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/apzXGEbZht0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">An example of the ‘still face experiment.’</span></figcaption>
</figure>
<p>During each visit, we measured infants’ stress by collecting saliva samples to look at changes in cortisol. We also collected information on how many depression symptoms mothers were feeling. Finally, when the infants were 18 months of age, we brought the families back into our lab and collected saliva to measure the length of the infant’s telomeres.</p>
<p>Worsening depression symptoms in mothers related to greater infant cortisol stress responses between 6 and 12 months of age. In addition, infants with higher cortisol stress responses were more likely to have shorter telomeres at 18 months of age, indicating greater cellular wear and tear.</p>
<h2>Better mental health</h2>
<p>While these findings are preliminary and should be replicated with a larger group of infants, our results highlight how patterns of health across the lifespan may be influenced in the first 18 months of life. This early stress may put young children on track for the early onset of poor health outcomes. </p>
<p>The silver lining is that infancy is a sensitive developmental period, when humans are especially responsive to their environments. Fostering positive experiences between infants and their mothers – as well as providing affordable, scientifically supported treatment services for mothers experiencing depression – may allow infants to move toward a healthier life trajectory.</p>
<p>In our view, these results show how important it is to fund effective maternal mental health treatment and early childhood policies.</p><img src="https://counter.theconversation.com/content/89357/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Benjamin W. Nelson received funding from the Mind and Life Institute to conduct this research.</span></em></p><p class="fine-print"><em><span>Heidemarie Laurent received funding from the Society for Research on Child Development to conduct this study.</span></em></p><p class="fine-print"><em><span>Nick Allen does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>At less than 2 years old, children of mothers with increasing depressive symptoms can show signs of added stress and quicker cellular aging.Benjamin W. Nelson, Doctoral Student in Clinical Psychology, University of OregonHeidemarie Laurent, Assistant Professor of Psychology, University of Illinois at Urbana-ChampaignNick Allen, Professor of Psychology and Director of the Center for Digital Mental Health, University of OregonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/730312017-02-17T16:34:05Z2017-02-17T16:34:05ZMore lessons from Dolly the sheep: Is a clone really born at age zero?<figure><img src="https://images.theconversation.com/files/157348/original/image-20170217-10195-zo9i2d.png?ixlib=rb-1.1.0&rect=4%2C1527%2C3275%2C2965&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">More Dollies, cloned from the same cell line.</span> <span class="attribution"><span class="source">Courtesy of Kevin Sinclair, University of Nottingham</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>In 1997 <a href="http://doi.org/10.1038/385810a0">Dolly the sheep was introduced</a> to the world by biologists Keith Campbell, Ian Wilmut and colleagues. Not just any lamb, Dolly was a clone. Rather than being made from a sperm and an egg, she originated from a mammary gland cell of another, no-longer-living, six-year-old Fynn Dorset ewe. </p>
<p>With her birth, a scientific and societal revolution was also born.</p>
<p>Some prominent scientists <a href="http://www.nytimes.com/1998/01/30/us/with-no-other-dollys-cloning-report-draws-critics.html">raised doubts</a>; it was too good to be true. But more animals were cloned: first the <a href="http://doi.org/10.1038/28615">laboratory mouse</a>, then <a href="http://doi.org/10.1126/science.280.5367.1256">cows</a>, <a href="http://doi.org/10.1038/8632">goats</a>, <a href="http://doi.org/10.1038/35024082">pigs</a>, <a href="http://doi.org/10.1038/424635a">horses</a>, even <a href="http://doi.org/10.1038/436641a">dogs</a>, <a href="http://doi.org/10.1016/j.ydbio.2006.02.016">ferrets</a> and <a href="http://doi.org/10.1095/biolreprod.109.081083">camels</a>. By early 2000, the issue was settled: Dolly was real and cloning adults was possible.</p>
<p>The implications of cloning animals in our society were self-evident from the start. Our advancing ability to reprogram adult, already specialized cells and start them over as something new may one day be the key to creating cells and organs that match the immune system of each individual patient in need of replacements.</p>
<p>But what somehow got lost was the fact that a clone was born – at day zero – created from the cell of another animal that was six years old. Researchers have spent the past 20 years trying to untangle the mysteries of how clones age. How old, biologically, are these animals born from other adult animals’ cells?</p>
<h2>Decades of cloning research</h2>
<p>Dolly became an international celebrity, but she was not the first vertebrate to be cloned from a cell taken from the body of another animal. In 1962, developmental biologist <a href="http://doi.org/10.1083/jcb.1812pi">John Gurdon</a> <a href="http://dev.biologists.org/content/develop/10/4/622.full.pdf">cloned the first adult animal</a> by taking a cell from the intestine of one frog and injecting it into an egg of another. Gurdon’s work did not go unnoticed – he went on to share the <a href="https://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/popular-medicineprize2012.pdf">2012 Nobel Prize</a> in Physiology or Medicine. But it was Dolly who had captured our imagination. Was it because she was a warm-blooded animal, a mammal, much closer to human? If you could do it in a sheep, you could do it on us!</p>
<p>Dolly, along with Gurdon’s frogs from 35 years earlier and all the other experiments in between, redirected our scientific studies. It was amazing to see a differentiated cell – an adult cell specialized to do its particular job – transform into an embryonic one that could go on to give rise to all the other cells of a normal body. We researchers wondered if we could go further: Could we in the lab make an adult cell once again undifferentiated, without needing to make a cloned embryo?</p>
<p>A decade after Dolly was announced, stem cell researcher <a href="https://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/yamanaka-facts.html">Shynia Yamanaka’s team</a> did just that. He went on to be the Nobel corecipient with Gurdon for showing that mature cells could be <a href="http://doi.org/10.1016/j.cell.2006.07.024">reprogrammed to become pluripotent</a>: able to develop into any specialized adult cell.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/157263/original/image-20170217-4280-lo3qhr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/157263/original/image-20170217-4280-lo3qhr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/157263/original/image-20170217-4280-lo3qhr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=390&fit=crop&dpr=1 600w, https://images.theconversation.com/files/157263/original/image-20170217-4280-lo3qhr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=390&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/157263/original/image-20170217-4280-lo3qhr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=390&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/157263/original/image-20170217-4280-lo3qhr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=490&fit=crop&dpr=1 754w, https://images.theconversation.com/files/157263/original/image-20170217-4280-lo3qhr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=490&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/157263/original/image-20170217-4280-lo3qhr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=490&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An adult body cell can be made into an induced pluripotent stem cell that in turn can develop into any kind of differentiated cell.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/induced-pluripotent-stem-cell-ips-regenerative-363797669?src=2eqGFx-_3l5j5NslRYdyYA-1-17">Regenerative medicine image via www.shutterstock.com.</a></span>
</figcaption>
</figure>
<p>Now we have the possibility of making individualized replacement cells – potentially any kind – to replace tissue damaged due to injury, genetic disorders and degeneration. Not only cells; we may soon be able to have <a href="http://doi.org/10.1016/j.cell.2016.12.036">our own organs grown in a nonhuman host</a>, ready to be transplanted when needed.</p>
<p>If Dolly was responsible for unleashing the events that culminate with new methods of making fully compatible cells and organs, then her legacy would be to improve the health of practically all human beings on this planet. And yet, I am convinced that there are even better things to come.</p>
<h2>Dolly’s secrets still unfolding</h2>
<p>In the winter of 2013, I found myself driving on the wrong side of the road through the Nottingham countryside. In contrast to the luscious landscape, I was in a state gloom; I was on my way to see Keith Campbell’s family after his sudden death a few weeks earlier. Keith was a smart, fun, loving friend who, along with Ian Wilmut and <a href="http://dolly.roslin.ed.ac.uk/facts/the-life-of-dolly/">colleagues at the Roslin Institute</a>, had brought us Dolly 15 years earlier. We had met at a conference in the early 1990s, when we were both budding scientists playing around with cloning, Keith with sheep, me with cows. An extrovert by nature, he quickly dazzled me with his wit, self-deprecating humor and nonstop chat, all delivered in a thick West Midlands accent. Our friendship that began then continued until his death. </p>
<p>When I knocked at the door of his quaint farmhouse, my plan was to stay just a few minutes, pay my respects to his wife and leave. Five hours and several Guinnesses later, I left feeling grateful. Keith could do that to you, but this time it wasn’t him, it was his latest work speaking for him. That’s because his wife very generously told me the project Keith was working on at the time of his death. I couldn’t hide my excitement: Could it be possible that after 20 years, the most striking aspect of Dolly’s legacy was not yet revealed?</p>
<p>See, when Dolly was cloned, she was created using a cell from a six-year-old sheep. And <a href="http://dolly.roslin.ed.ac.uk/facts/the-life-of-dolly/">she died at age six and a half</a>, a premature death for a breed that lives an average of nine years or more. People assumed that an offspring cloned from an adult was starting at an age disadvantage; rather than truly being a “newborn,” it seemed like a clone’s internal age would be more advanced that the length of its own life would suggest. Thus the notion that clones’ biological age and their chronological one were out of sync, and that “cloned animals will die young.” </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/157265/original/image-20170217-4236-1ur3act.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/157265/original/image-20170217-4236-1ur3act.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/157265/original/image-20170217-4236-1ur3act.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=558&fit=crop&dpr=1 600w, https://images.theconversation.com/files/157265/original/image-20170217-4236-1ur3act.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=558&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/157265/original/image-20170217-4236-1ur3act.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=558&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/157265/original/image-20170217-4236-1ur3act.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=701&fit=crop&dpr=1 754w, https://images.theconversation.com/files/157265/original/image-20170217-4236-1ur3act.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=701&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/157265/original/image-20170217-4236-1ur3act.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=701&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Telomeres get clipped with each cell division, limiting how many times a cell can copy itself.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/telomere-cell-division-488807065">Chromosome image via www.shutterstock.com.</a></span>
</figcaption>
</figure>
<p>Some of us were convinced that if the cloning procedure was done properly, the biological clock should be reset – a newborn clone would truly start at zero. We worked very hard to prove our point. We were not convinced by a single DNA analysis done in Dolly showing slightly shorter <a href="http://learn.genetics.utah.edu/content/basics/telomeres/">telomeres</a> – the repetitive DNA sequences at the end of chromosomes that “count” how many times a cell divides. We presented strong scientific evidence showing that cloned cows had all the <a href="http://doi.org/10.1126/science.288.5466.665">same molecular signs of aging</a> as a nonclone, predicting a normal lifespan. Others <a href="http://doi.org/10.1038/35030301">showed the same in cloned mice</a>. But we couldn’t ignore reports from colleagues interpreting <a href="http://doi.org/10.1038/20580">biological signs in cloned animals</a> that they attributed to <a href="http://dx.doi.org/10.1095/biolreprod66.6.1649">incomplete resetting of the biological clock</a>. So the jury was out. </p>
<p>Aging studies are very hard to do because there are only two data points that really count: date of birth and date of death. If you want to know the lifespan of an individual you have to wait until its natural death. Little did I know, that is what Keith was doing back in 2012.</p>
<p>That Saturday afternoon I spent in Keith’s house in Nottingham, I saw a photo of the animals in Keith’s latest study: several cloned Dollies, all much older than Dolly at the time she had died, and they looked terrific. I was in awe.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/157344/original/image-20170217-10223-1ot826b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/157344/original/image-20170217-10223-1ot826b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/157344/original/image-20170217-10223-1ot826b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=327&fit=crop&dpr=1 600w, https://images.theconversation.com/files/157344/original/image-20170217-10223-1ot826b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=327&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/157344/original/image-20170217-10223-1ot826b.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=327&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/157344/original/image-20170217-10223-1ot826b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=410&fit=crop&dpr=1 754w, https://images.theconversation.com/files/157344/original/image-20170217-10223-1ot826b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=410&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/157344/original/image-20170217-10223-1ot826b.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=410&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Four 8-year-old Finn-Dorset clones born in July 2007 and derived from the mammary gland cell line that gave rise to Dolly.</span>
<span class="attribution"><a class="source" href="http://www.nature.com/articles/ncomms12359">K. D. Sinclair, S. A. Corr, C. G. Gutierrez, P. A. Fisher, J.-H. Lee et al. doi:10.1038/ncomms12359</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The data were confidential, so I had to remain silent until late last year when <a href="http://dx.doi.org/10.1038/ncomms12359">the work was posthumously published</a>. Keith’s coauthors humbly said: “For those clones that survive beyond the perinatal period […] the emerging consensus, supported by the current data, is that they are healthy and seem to age normally.” </p>
<p>These findings became even more relevant when last December researchers at the <a href="http://www.scripps.edu">Scripps Research Institute</a> found that induced pluripotent stem cells reprogrammed using the “Yamanaka factors” <a href="http://dx.doi.org/10.1038/nbt.3749">retain the aging epigenetic signature of the donor individual</a>. In other words, using these four genes to attempt to reprogram the cells does not seem to reset the biological clock. </p>
<p>The new Dollies are now telling us that if we take a cell from an animal of any age, and we introduce its nucleus into a nonfertilized mature egg, we can have an individual born with its lifespan fully restored. They confirmed that all signs of biological and chronological age matched between cloned and noncloned sheep. </p>
<p>There seems to be a natural built-in mechanism in the eggs that can rejuvenate a cell. We don’t know what it is yet, but it is there. Our group as well as others are hard at work, and as soon as someone finds it, the most astonishing legacy of Dolly will be realized.</p><img src="https://counter.theconversation.com/content/73031/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>José Cibelli does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>It took years of attempts before scientists were able to clone a mammal from an adult cell. And with that success came plenty more questions.José Cibelli, Scientific Director LARCEL-BIONAND, Spain and Professor of Animal Biotechnology, Michigan State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/519232015-12-08T14:07:11Z2015-12-08T14:07:11ZFive surprising findings about death and dying<figure><img src="https://images.theconversation.com/files/104647/original/image-20151207-3131-phvx7h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Just thinking about death triggers odd behaviour, shows research.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Near-Death-Experience_Illustration.jpg">Jesse Krauß/wikimedia</a></span></figcaption></figure><p>In this world nothing can be said to be certain, except death and taxes, as Benjamin Franklin <a href="http://www.ncbi.nlm.nih.gov/pubmed/22390145">famously wrote</a>. Few of us find taxes exciting, but <em>death</em> – even just thinking about it – affects us profoundly in many different ways. This is why researchers across so many different fields study it from their perspectives. </p>
<p>Here are five research findings – biochemical, medical, genetic, sociological and psychological – that you may not be aware of.</p>
<h2>1. Decomposing human flesh smells (sickly) sweet</h2>
<p>It is difficult to describe what the <a href="https://theconversation.com/the-smell-of-death-its-chemical-pattern-could-become-a-powerful-forensic-tool-47966">stench of death</a> is like, but most people agree it is bad. However, the smell of human decomposition is actually very complex, involving over <a href="http://www.compoundchem.com/2014/10/30/decompositionodour/">400 volatile chemical compounds</a>. </p>
<p>We share many of these with other animals, but a <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137341">recent study</a> found that there might be five <a href="http://www.bbc.co.uk/schools/gcsebitesize/science/triple_aqa/alcohols_carboxylic_acids_esters/esters/revision/1/">esters</a> – organic compounds that react with water to produce alcohols and acids – that are unique to humans. This is compared to 26 in other animal species from frogs and robins to pigs. The interesting thing about them is that they are also produced by fruits, especially when they rot. Those familiar with the smell, such as forensic scientists or morticians, often report a “sickly sweet” smell when describing corpses. Now we might know why.</p>
<h2>2. No, your nails and hair won’t keep growing</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/104652/original/image-20151207-3125-1dr1d5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/104652/original/image-20151207-3125-1dr1d5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/104652/original/image-20151207-3125-1dr1d5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/104652/original/image-20151207-3125-1dr1d5l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/104652/original/image-20151207-3125-1dr1d5l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/104652/original/image-20151207-3125-1dr1d5l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/104652/original/image-20151207-3125-1dr1d5l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/104652/original/image-20151207-3125-1dr1d5l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Finally no more hairstyle appointments.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/jnissa/608764942/in/photolist-cexmZb-cfXX6f-wD2dnr-byBHHp-nAmWMn-ca3aVA-oMGkCE-a8uNkS-d9QTP2-c7Mg3N-ca3amC-ptSGH-oRPwL8-9LFTTw-d9QUM7-c7MkoN-a24cSu-oMFRKs-aahxXi-8QBGvS-oqYXRJ-qThjeT-9ACocT-aVej2R-VN5Bh-jbUXvz-6ReK2K-dwRFxh-4B3rzZ-aAL3ht">Jocelyn Saurini/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>You may have heard that our nails and hair keep growing – at least for a while – after we die. This conjures up creepy images of exhumed corpses with an urgent need for barbers or pedicurists. The idea probably came from actual observations of hair and nail “growth”, but it’s all an illusion. The truth is that the rest of our bodies shrink due to dehydration, making the nails and hair look longer. </p>
<p>What we think of as hair and nails are actually <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.013734">already dead</a>: the only living parts are the the hair follicle and nail matrix under the skin. But these organs require hormonal regulation to produce hair and nails, not to mention the supply of ingredients like proteins and oils which cease upon death, or very soon after. </p>
<h2>3. Telomere length predicts lifespan</h2>
<p>For a long time we thought that our cells might be immortal, and that under the right environmental conditions, they would go on replicating forever. But, <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137341">as discovered</a> in 1961, they don’t: after some 50 to 70 divisions, they stop. A decade later <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137341">a hypothesis</a> was put forward: telomeres – repeated DNA sequences at the ends of our chromosomes – shorten with every division, and when they get too short, divisions stop and the cells die. </p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/104656/original/image-20151207-3116-1adj71r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/104656/original/image-20151207-3116-1adj71r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/104656/original/image-20151207-3116-1adj71r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/104656/original/image-20151207-3116-1adj71r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/104656/original/image-20151207-3116-1adj71r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/104656/original/image-20151207-3116-1adj71r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/104656/original/image-20151207-3116-1adj71r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/104656/original/image-20151207-3116-1adj71r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Shorter chromosome ends (telomeres) means shorter lifespan.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/ajc1/10085714333/sizes/o/">AJCann/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Since then, there has been <a href="http://jnci.oxfordjournals.org/content/107/6/djv074.short">increasing evidence</a> that telomere length can be used to predict lifespan, and <a href="http://www.ncbi.nlm.nih.gov/pubmed/23260664">not just in humans</a>. However, <a href="http://biomedgerontology.oxfordjournals.org/content/66A/2/202.full">not all research</a> confirms this, and it is not yet clear whether shortened telomeres are the cause of ageing or just a symptom. If telomere length does control ageing, then it may be possible to significantly lengthen lifespans by manipulating their length. At the moment we still know too little about telomeres to do this, but watch this space.</p>
<h2>4. The fear of death declines with age</h2>
<p>It seems counter-intuitive to think that we would fear death less as we get older, but studies run in the United States have shown this is the case. <a href="http://geronj.oxfordjournals.org/content/32/1/76.short">One study</a> found that people in their 40s and 50s, expressed greater fears of death than those in their 60s and 70s. Similarly, <a href="http://www.drpaulwong.com/wp-content/uploads/2013/09/1987-Gesser-Wong-Reker-Death-Attitude-Profile.pdf">another study</a> found that people in their 60s reported less death anxiety than both people in middle age (35 to 50 years) and young adults (18 to 25 years).</p>
<p><a href="http://www.pnas.org/content/107/22/9985.abstract">Yet another study</a> found that after a peak in their 20s, participants’ death anxiety tended to decline with age. For men, the decline plateaued in their 60s, whereas for women, there was some evidence for a slight bump between their 40s and 50s. I found similar patterns in my own research for a <a href="http://www.bloomsbury.com/us/death-anxiety-and-religious-belief-9781472571625/">forthcoming book</a> – but only in the United States. I saw no such trends in Brazil, the Philippines, Russia, and South Korea.</p>
<p>All of these studies also survey people of different ages but fail to follow individuals across their lifespans. It is therefore possible that the relationship between age and death anxiety is driven by a generational effect: maybe our forebears were just made of sterner stuff than we are.</p>
<h2>5. Thinking about death makes us prejudiced</h2>
<p>Briefly describe the emotions that the thought of your own death arouses in you. Jot down what you think will happen to you physically as you die and once you are physically dead. These are instructions that have been given to thousands of people across over <a href="http://psr.sagepub.com/content/14/2/155.long">200 studies</a> over the past 25 years.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/104661/original/image-20151207-3154-1ixei30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/104661/original/image-20151207-3154-1ixei30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/104661/original/image-20151207-3154-1ixei30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/104661/original/image-20151207-3154-1ixei30.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/104661/original/image-20151207-3154-1ixei30.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/104661/original/image-20151207-3154-1ixei30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/104661/original/image-20151207-3154-1ixei30.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/104661/original/image-20151207-3154-1ixei30.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Does regular contemplation of death make you a bigot?</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/jdhancock/8703995094/in/photolist-eg9fuW-9atqQ-rhH2vz-9CyDT-qpYDPb-ffLahJ-fcM268-osDRbc-2twRrQ-iYZum-8Kg9PV-4a6BaC-ffU3TS-kku4Np-A2zwzi-8HHUqG-dKURbJ-8vRkqQ-dssekL-wirzLb-4y9XXp-gJVNvx-639MnV-5ZJtAd-2unXKb-36wPw3-8mQpt3-bepe2Z-4Zwfhh-eDDXQy-xJpJ35-bGDGt6-NnEbG-bYnbSY-BHiCvh-xTogv1-awiHg8-c3mdQE-BnqJsS-a9Scvj-6CLi9o-diPmms-bJtJHa-2y8Vbg-8FSNZg-dzYfmN-vC3WEK-4oWk8u-dhcF1o-8SxTyh">JDHancock/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The results suggest that thinking about death – compared to thinking about more banal stuff, or even other sources of anxiety – makes people <a href="http://link.springer.com/article/10.1023/A:1010613909207">more tolerant of racists</a>; <a href="http://people.uncw.edu/ogler/Experimental/TM%201.pdf">harsher toward prostitutes</a>; <a href="http://www.sciencedirect.com/science/article/pii/S0022103108000991">less willing to consume foreign goods</a>; and even makes liberals <a href="http://www.sciencedirect.com/science/article/pii/S0022103109000948">less supportive of LGBT rights.</a>. </p>
<p>However, it also makes people <a href="http://www.ncbi.nlm.nih.gov/pubmed/16060742">want to have more children</a> and to <a href="http://people.uncw.edu/ogler/Experimental/TMT%20offspring%202.pdf">name their children after themselves</a>. In other words, thinking about death makes us want to pursue symbolic immortality, the vicarious living on through our offspring or through groups we identify with. There is even some evidence that, in the face of death, nonreligious people are <a href="https://journals.equinoxpub.com/index.php/JCSR/article/view/17287">more willing to believe in God</a> and <a href="http://www.ncbi.nlm.nih.gov/pubmed/21995319">an afterlife</a>.</p><img src="https://counter.theconversation.com/content/51923/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jonathan Jong receives funding from The Royal Society of New Zealand to study the relationship between death anxiety and religious belief.</span></em></p>It’s a myth that hair and nails continue to grow after you die. What else have science discovered about death?Jonathan Jong, Research Fellow, Coventry UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/488002015-10-08T21:32:56Z2015-10-08T21:32:56ZChemistry Nobel DNA research lays foundation for new ways to fight cancer<figure><img src="https://images.theconversation.com/files/97830/original/image-20151008-9679-pj29id.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">You'd be in bad shape if your cells couldn't fix DNA issues that arise.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/redondoself/3354943757">redondoself</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Our cells are up against a daily onslaught of damage to the DNA that encodes our genes. It takes constant effort to keep up with the DNA disrepair – and if our cells didn’t bother to try to fix it, we might not survive. The DNA damage repair pathways are an essential safeguard for the human genome.</p>
<p>The <a href="http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2015/press.html">2015 Nobel Laureates in chemistry</a> received the prize for their pioneering work figuring out the molecular machinery that cells use to repair that DNA damage. In their basic research, <a href="http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2015/lindahl-interview.html">Tomas Lindahl</a>, <a href="http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2015/modrich-interview.html">Paul Modrich</a> and <a href="http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2015/sancar-interview.html">Aziz Sancar</a> each narrowed in on one piece of the DNA repair puzzle.</p>
<p>They’ve laid the framework for the research that many basic and translational scientists are expanding upon to try to crack cancer. Ironically, we’re finding ways to turn that DNA repair system against cancerous cells that have often arisen from DNA damage in the first place. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/97832/original/image-20151008-26883-2grjpe.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/97832/original/image-20151008-26883-2grjpe.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/97832/original/image-20151008-26883-2grjpe.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=463&fit=crop&dpr=1 600w, https://images.theconversation.com/files/97832/original/image-20151008-26883-2grjpe.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=463&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/97832/original/image-20151008-26883-2grjpe.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=463&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/97832/original/image-20151008-26883-2grjpe.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=582&fit=crop&dpr=1 754w, https://images.theconversation.com/files/97832/original/image-20151008-26883-2grjpe.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=582&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/97832/original/image-20151008-26883-2grjpe.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=582&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">UV light from the sun is one cause of DNA mutations.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:DNA_UV_mutation.png">NASA/David Herring</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>DNA under siege</h2>
<p>DNA is composed of four simple letters, or nucleotides, A, T, C and G. When combined, these nucleotides form the genetic code. There are <a href="https://www.genome.gov/11006943">approximately 30,000 genes</a> in the human genome. </p>
<p>Each time a cell grows and divides, every single gene needs to be faithfully copied to the next generation of cells. This process of DNA replication is constantly threatened by both internal and external sources of DNA damage. There are environmental sources such as radon from the earth or UV light from the sun. Or it can be just a mistake, happening within the cell as a consequence of normal growth and division. Some studies have estimated that a single cell can experience <a href="http://doi.org/10.1128/9781555816704">several thousand DNA damage events in a single day</a>.</p>
<p>The question then becomes: how does the cell repair all of this damage? Or perhaps more worrisome, what happens if the cell doesn’t repair the damage?</p>
<h2>A full toolbox to deal with the damage</h2>
<p>To counter the daily onslaught of DNA damage, mammalian cells have evolved a number of intricate mechanisms to not only recognize DNA damage, but repair it and restore the original genetic sequence.</p>
<p>Consider a typo that changes the letter N to the letter M, causing “grin” to become “grim.” That single typo has now changed the entire meaning of the word. It works just the same in the “words” of the genetic code when an incorrect nucleotide takes the place of the right one. The DNA damage repair enzymes function like an eraser reverting the mutant M back to the original N. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/97829/original/image-20151008-9659-yrqfn.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/97829/original/image-20151008-9659-yrqfn.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/97829/original/image-20151008-9659-yrqfn.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=794&fit=crop&dpr=1 600w, https://images.theconversation.com/files/97829/original/image-20151008-9659-yrqfn.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=794&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/97829/original/image-20151008-9659-yrqfn.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=794&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/97829/original/image-20151008-9659-yrqfn.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=997&fit=crop&dpr=1 754w, https://images.theconversation.com/files/97829/original/image-20151008-9659-yrqfn.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=997&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/97829/original/image-20151008-9659-yrqfn.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=997&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">DNA excision repair gets rid of a mistaken nucleotide and fills in what should be there.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Dna_repair_base_excersion_en.svg">LadyofHats</a></span>
</figcaption>
</figure>
<p>Following DNA damage, the cell must first recognize the damage and then alert the system that there’s a problem. The recognition machinery then activates various factors to halt cell growth until the damage has been repaired. And if things are too far gone, additional factors are poised and ready to induce cell death.</p>
<p>That’s the most basic way to think about the DNA damage response pathway, as a simple chain of events. Of course it’s a lot more complicated, a complex network of checks and balances to ensure that the DNA damage is not only recognized but clearly identified to ensure that the correct factors are recruited to repair the lesion.</p>
<p>Much like a homeowner wouldn’t want an electrician to fix the leaky roof, a DNA “typo” shouldn’t be fixed by a mechanism used to heal double-strand DNA breaks, for instance. Therefore, sensing which specific genetic lesion is the problem is one of the earliest and most critical steps in the DNA damage response pathway.</p>
<p>It’s hard to say exactly how many DNA damage response “sensors” there are or exactly who they are, but that’s something the field is actively investigating. Likewise, while the number of DNA damage repair pathways we know about hasn’t necessarily increased since the groundbreaking Nobel work was done, the complexity of our understanding has.</p>
<h2>What if the repair process itself is broken?</h2>
<p>In a limited capacity, mutations actually aid evolution. There have to be changes for natural selection to act on, so these DNA mutations are a significant factor in Darwin’s theory of evolution. However, what is a blessing may also be a curse.</p>
<p>Mutations in essential genes can <a href="http://www.ncbi.nlm.nih.gov/pubmed/11792820">lead to death</a> even before we enter the world. However, mutations in nonessential genes may not be evident until later in life. When these mutations persist – or even worse, accumulate – it can lead to genomic instability. And that’s a hallmark of cancer cells.</p>
<p>You can imagine, then, that a single mutation in a component of the DNA damage response pathway could lead to the accumulation of DNA damage, genomic instability and ultimately the progression toward cancer. And it’s true, we frequently find mutations in the DNA damage response pathway in cancer. Deciphering exactly how these pathways work is essential to our understanding not only of cancer, but also of how we might exploit these pathways to actually treat the disease.</p>
<h2>Harnessing the repair systems to our own ends</h2>
<p>These damage repair pathways are essential to prevent the accumulation of genetic lesions and ultimately inhibit the progression toward cancer. Is there a way we can exploit the system, push it over the edge and cause an unwanted cell not just to gain mutations but to die?</p>
<p>To that end, researchers are hard at work trying to further define the nitty gritty details that regulate the DNA damage response. Others are trying to identify factors that we could target therapeutically.</p>
<p>It may seem counterintuitive to target the DNA damage response pathway once it’s already been inactivated by a mutation. But the approach has its advantages.</p>
<p>Generally, when a genetic mutation inactivates one branch of repair, the cell will try to compensate by using another type of repair just to keep the cell alive. Would you rather call the electrician and hope he can fix the leaky roof or risk having the entire roof collapse in on you?</p>
<p>The cell opts for a back-up mechanism to try to resolve the damage. In general, this results in inadequate repair and the acquisition of additional mutations, fueling the genomic instability and cancer progression.</p>
<p>We want to eliminate the back-up mechanism – send the electrician out of town. Research has demonstrated that when one type of repair mechanism is inactivated by a genetic mutation and you therapeutically inactivate the back-up mechanism, the cancerous cell dies. Likewise, if we combine drugs that induce a particular type of damage and then inactivate that specific repair pathway, cells die. Clinical scientists have demonstrated that this can lead to tumor regression in patients sparking a <a href="http://doi.org/10.2217/fon.14.60">surge of research in this area</a>.</p>
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<figcaption>
<span class="caption">In these dividing cells, DNA is colored white. They were treated with ATR molecules that interfere with DNA damage repair.</span>
<span class="attribution"><span class="source">Dr Neil J Ganem, Boston University</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Targeting telomeres</h2>
<p><a href="http://www.bumc.bu.edu/busm-pm/research/laboratories/laboratory-of-genome-instability-and-cancer-therapeutics/">My lab</a> is interested in understanding how the DNA damage response is regulated specifically at telomeric DNA.</p>
<p>The telomere is a repetitive DNA sequence that caps the ends of each human chromosome. Telomeres function as a barrier, protecting the human genome from degradation and/or the fusion of whole chromosomes.</p>
<p>Each time a cell divides, a portion of this barrier is lost; over time the shortened telomere compromises the genome’s stability. To avoid damage to the genome, critically short telomeres send a signal to the cell to either stop growing or induce cell death.</p>
<p>Cancer cells, however, have evolved mechanisms to overcome progressive telomere shortening and bypass this growth arrest. In other words, they outmaneuver the normal routine, dividing and growing while avoiding the usual step of telomere shortening that eventually leads to death for normal cells. One way they counter telomere shortening and promote telomere elongation is by <a href="http://doi.org/10.1038/nrg2763">activating the Alternative Lengthening of Telomeres pathway</a> (ALT). </p>
<p>The <a href="http://www.the-scientist.com/?articles.view/articleNo/42444/title/Control-ALT--Delete-Cancer/">ALT mechanism is active</a> in 10%-15% of <a href="http://doi.org/10.1016/j.ajpath.2011.06.018">all human cancers</a>. This incidence skyrockets to approximately 60% in some of the most aggressive forms of human cancer, including osteosarcoma and glioblastoma. These cancers are often resistant to common therapeutic strategies and there are no therapies that specifically target the ALT pathway.</p>
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<figcaption>
<span class="caption">Representative chromosome spread from ALT cells where telomeres are stained with either a red or green probe. A yellow signal indicates a recombination event between red and green telomere ends.</span>
<span class="attribution"><span class="source">Rachel Litman Flynn</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>In my lab, we’re focusing on one of the molecules that senses DNA damage in the first place, the ATR kinase. We’ve found that preventing it from doing its job leads to both a decrease in recombination at telomeres and an increase in telomere loss at the chromosome ends, suggesting a defect in ALT activity.</p>
<p>Perhaps most significant is that ATR inhibitions led to <a href="http://doi.org/10.1126/science.1257216">catastrophic cell division and robust cell death</a> in ALT-positive cancer cells, yet had little effect on non-cancerous cell lines.</p>
<p>These studies may allow us to drive ATR inhibitors into preclinical development with the ultimate goal of improving the therapeutic strategies in the treatment of some of the most aggressive forms of human cancer.</p>
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<figcaption><span class="caption">Time-lapse live-cell imaging experiment from the author’s lab investigating how to disrupt cancer cells by disrupting telomere maintenancete.</span></figcaption>
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<p>It’s this kind of translational research that builds on the framework laid by the work of our newest Nobel laureates in chemistry. Their basic research is proving to be the foundation for new ways to target – and hopefully treat – cancer.</p><img src="https://counter.theconversation.com/content/48800/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rachel Litman Flynn receives funding from the NIH-NCI and Karin Grunebaum Research Foundation. </span></em></p>Cells must repair the thousands of bits of DNA damage they incur every day. These cellular mechanisms fend off cancerous tumors, and cancer researchers are working to harness their power.Rachel Litman Flynn, Assistant Professor of Pharmacology and Medicine, Boston UniversityLicensed as Creative Commons – attribution, no derivatives.