As fathers age, certain harmful mutations are favored during sperm production.
Choosing or finding yourself having children at an advanced age can entail additional risks for the health of the unborn child: this also applies if the older one is the father. Sperm from older fathers are significantly more likely to carry harmful mutations. In fact, as we age, some dangerous mutations gain a biological advantage during sperm production. And they can thus multiply exponentially. This was revealed by an analysis published on Nature.
More informed decisions
It has long been known that the risk of genetic diseases in children increases as the parents’ age increases, but until now it was thought that the number of mutations in sperm rose steadily as the years passed, due to the accumulation of random mutations. The new study reveals, however, that in older fathers, harmful genetic mutations in sperm (which are passed on to the next generation) not only accumulate, but are also favored during the production of sperm in the testicles.
Among men who become fathers in their early 30s, about one in 50 sperm has a mutation that can cause disease. In 70-year-old fathers, this percentage rises to one sperm in 20. Knowing this can help those who wish to postpone fatherhood to make informed decisions, for example deciding to freeze seminal fluid for later use.
Sperm analyses
A group of scientists coordinated by the Wellcome Sanger Institute, in the United Kingdom, used an ultra-accurate DNA sequencing technique to analyze the sperm of 81 healthy men, aged between 24 and 75. The goal was to map how harmful mutations accumulate in sperm as they age.
In addition to observing that the risk of sperm carrying dangerous genetic mutations increases with the age of fathers, researchers have identified 40 genes in which certain changes in DNA gain a biological advantage during sperm production: among these there are several genes whose mutations are linked to neurodevelopmental disorders in children or the risk of developing tumors.
The Mutant Advantage
The exponential growth of spermatozoa with mutations is due to a form of natural selection that acts on the stem cells that give rise to spermatozoa: some mutations cause them to divide abnormally, creating a greater number of copies and giving them a competitive advantage during the production of male sexual cells.
The fact that “mutant” sperm grow exponentially with increasing age means, in simple terms, that postponing fatherhood by one year in the 30s has a different weight than postponing it by a year after the age of 50.
Consequences to be explored further
It remains to be understood how the accumulation of unfavorable mutations in the sperm of older fathers translates into the health of their children. Bearing in mind that not all sperm with harmful mutations manage to reach conception or give rise to life. Some of these can negatively impact fertility or embryonic development, or even increase the risk of spontaneous abortions.