Men’s ‘biological clock’ linked to schizophrenia and autism

Men play an equal, if not larger, role in passing on genetic mutations to their children. Bettina Neuefeind

We all know about the reproductive “biological clock” in women reminding them of the finite time in which they can have children. Now researchers have found evidence that men also have a reproductive “best before” date.

Women are born with a certain number of eggs and as they age, the quantity and quality of these eggs decreases. By the time she’s in her mid- to late-30s, the chances of a woman’s eggs having an incorrect number of chromosomes, leading to disorders and diseases such as Downs Syndrome (characterised by an extra chromosome), dramatically increases.

By the time the woman is in her 40s, the chances of her becoming pregnant without medical intervention or using her own eggs is extremely low.

Men, in comparison, are generally thought to be able to father children at any age. Think of Charlie Chaplin, who had his last child at the ripe age of 72. This is largely because new (de novo) sperm production (spermatogenesis) occurs throughout adult life, regardless of age.

But wait

This picture is now changing. A recent study published in the peer-reviewed journal Nature demonstrates that as a man ages, the chances of his sperm containing more mutations within his genes also increases.

The researchers found children of older fathers had a greater chance of developing autism and schizophrenia.

The study authors studied the genomes of mothers, fathers and their children in Iceland to identify SNPs or “snips” (single nucleotide polymorphisms), the equivalent of a single letter change in a word. Similarly to changes in spelling for text messaging have altered the English language, SNPs may, in fact, be a natural part to evolution – not all mutations are bad.

SNPs seen in the child and not the parents are new mutations thought to result from changes within the egg or sperm itself. And some of them cause diseases.

Although both parents contribute equally to the genetic material of their children, the study also showed that fathers may contribute more new gene mutations in their children than mothers. Men passed on an average of 55 gene mutations to their children, compared to 14 gene mutations from the mother. This is most likely because the maternal egg reserve is established prior to birth, compared to the constant cell division and production of new sperm in males throughout life.

Women are not the only ones to have a reproductive ‘best before’ date. Daniel Oines

The researchers also found a significant relationship between the father’s age at conception and the number of mutations in his sperm: a 22-year-old passed on 39 gene mutations to his child compared to 91 gene mutations from a 40-year-old man. They predict that the number of new mutations in a man’s sperm doubles every 16 and a half years.

How they did it

In a sense, the study worked backwards, starting with a disease and then looking at the incidences of new mutations in children. The authors recruited children with non-inheritable autism or schizophrenia and worked out their genetic profiles and that of their parents. They found a strong link between the paternal age, increases in new gene mutations and the prevalence of these diseases.

The finding aligns with the increase in autism and schizophrenia diagnoses in the Western world and increasing parental age. But it’s unlikely to hold the solution because of the high variability in the characteristics of autism and the possibility that it is the result of many rather than a single gene mutation.

A limitation of the study as that it focused on children who were diagnosed as autistic or schizophrenic, and then looked at the correlation between paternal age and de novo mutations in children. The incidence of autism and schizophrenia and its link with paternal age in the general public is unknown.

Bu it’s not all bad news. The majority of new gene mutations are not associated with diseases and poor health outcomes for the child.

This is an important finding, especially given that more people are having children later in life. There’s already a push for increased public awareness of the impact of age and lifestyle on female fertility. But fathers’ age is commonly ignored. This clearly needs to change since men play an equal, if not larger, role in passing on mutations to their children and this impacts their health.

What this study does is demonstrate that there may be gender equality in reproductive “best before” dates and that the biological clock exists in both women and men.