Children conceived by older parents have a higher risk of inheriting genetic diseases and certain types of cancer, and researchers have recently discovered why.

As numerous studies in recent years have shown, the father’s age at conception is more important than the mother’s age in terms of the genetic mutations they can pass on to their children.

According to a study published in the journal Nature in 2012, with each year that passes until the moment of conception, a person passes on two more genetic mutations.

A man who becomes a father in his 20s passes on an average of 25 mutations to his child, while a father in his 40s passes on about 65 mutations, the cited study claims.

The increasing age of parents at the time of conception may be one of the reasons for the increase in the incidence of diseases such as autism and schizophrenia.

For example, a 40-year-old father’s risk of having a child with autism is twice as high as a 20-year-old father’s. The reasons why parents who survive adulthood pass on more genetic mutations to their children have long remained unknown.

Recently, researchers have discovered mechanisms that may explain the risk of genetic diseases in humans.

Genetic mutations are transmitted more easily

According to the results of a new study published in
nature.com/articles/s41559-022-01958-x” target=”_blank”>Nature Ecology&Evolution and conducted by researchers from Rockefeller University, USA. They studied mutations that occur during spermatogenesis – the process of sperm formation from germ cells – in laboratory in studies of fruit flies, American researchers noticed that mutations were more numerous in the testes of old males than of young ones.

Furthermore, many of these mutations appear to be eliminated in young parents during spermatogenesis by specific genome repair mechanisms. Next, the scientists tried to find out whether the repair mechanisms are less effective in older men, or whether this is due to a greater number of germ cell mutations. “Our results show that both reasons are valid.

At each stage of spermatogenesis, older flies have more mutations per RNA molecule than young ones,” explained Evan Witt, study coordinator and bioinformatics specialist.

Output mechanisms do not work

The genome, the set of genes that contain an individual’s genetic information, has a number of repair mechanisms.

Of all the organs in the body, the testicles have the highest level of gene expression. Furthermore, genes that are highly expressed during spermatogenesis tend to have fewer mutations than those that are not as well expressed. It may seem counterintuitive, but it makes sense: One theory to explain why the testes express so many genes suggests that it may be a kind of genomic surveillance mechanism—a way of identifying and eliminating problematic mutations.

In the case of “older” sperm, the researchers found that genetic mutations are transmitted much more easily because this mechanism is not working. For this study, researchers at Rockefeller University’s Laboratory of Evolutionary Genetics and Genomics sequenced single-cell RNA extracted from the germ cells of about 300 fruit flies, about half of which were young (48 hours old) and the rest considered old during their life cycle (25 days ).

Vinegar shrews have an increased reproduction rate, and the study of their mutations can provide new knowledge about humans. What is certain is that “if people inherit more mutations from older parents, this will increase the risk of new genetic disorders or cancer,” concludes Evan Witt, the study’s coordinator.

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