14 October 2022

Biological age of sperm

Epigenetic changes in the sperm of older men can affect the health of their children


An international team of scientists has shown that with age, genetic and epigenetic (not affecting the DNA sequence) changes accumulate in mammalian spermatozoa, which can affect the activity of some genes and, as a result, the health of offspring. In the future, it remains to be seen whether this process is reversible.

The results of the study, supported by a grant from the Russian Science Foundation (RNF), are published in the journal Human Reproduction Update (Ashapkin et al., Age-associated epigenetic changes in mammalian sperm: implications for offspring health and development).

The number of children born from age-related fathers is increasing in the modern world. The fertility of men, that is, the ability to conceive a child, decreases with age, however, unlike women, they have a chance of natural conception almost until old age.

Spermatozoa are formed during the division of progenitor germ cells throughout life, while in women the stock of future eggs is finally formed in the mother's womb. When a cell divides, new copies of DNA are formed on an existing one, as on a matrix, but sometimes copying occurs with errors. A large number of new divisions — and a man has about 23 of them per year, that is, every 16 days — is accompanied by the risk of new mutations. With age, the progenitor cells of spermatozoa divide more and more, and at the same time more and more errors accumulate in their DNA.

The cause of changes in the hereditary material of germ cells can be not only mutations. So, during life, various tags are sometimes attached to genes. They do not change the DNA itself, but serve as a regulatory signal: they can turn on, turn off genes or change their mode of operation. Such labels are called epigenetic, that is, "supra-genetic". There is an assumption that due to epigenetic changes in the germ cells, parents can pass on to their offspring not only the program of development of the organism embedded in the genes, but also information about the environment in which children will grow and develop.

Scientists from the Research Institute of Physico-Chemical Biology named after A.N. Belozersky Moscow State University (Moscow) The School of Public Health and Medical Sciences of the University of Massachusetts at Amherst (USA) and the Center for Molecular Medicine and Genetics of the Wayne State University School of Medicine (USA) the results of studies on age-related epigenetic marks in mammalian spermatozoa and their impact on the health of offspring were analyzed and summarized.


The most important factors on the part of the father and mother, influencing through changes in the germ cells on the health of children. A drawing from the article by Ashapkin et al. – VM.

One of the most common epigenetic modifications is the methylation of the cytosine nucleotide — the addition of a small methyl group consisting of a carbon atom and three hydrogen atoms to one of the "bricks" of nucleic acid. Studies have shown that in genes associated with early fetal development and neuropsychiatric disorders, methylation changes with age, and in some areas the number of "tags" increases, while in others it decreases.

Several research teams were able to construct a sufficiently accurate (with an error of one and a half years) epigenetic clock of spermatozoa, allowing to determine the biological age of men. Moreover, it turned out that the increase in the "epigenetic" age is due to the fact that it takes longer for healthy married couples to conceive naturally. Also, with the help of these watches, it was shown that smoking accelerates the aging of spermatozoa. Shortly after fertilization, the embryo has a global erasure of the methyl tags inherited from the parents, but some modern studies suggest that epigenetic changes in the genome of sperm of older fathers may still be observed later in the descendants. The results have been demonstrated in many studies of various mammals (mice, rats and bulls) and in so far isolated studies in humans. Often it is assisted reproductive technologies, such as IVF and ICSI, that allow age couples to have children. Therefore, the authors of the review wondered whether these technologies themselves do not affect epigenetic changes in the fetus. 

One of the recent studies It was shown that with the artificial introduction of the selected sperm into the egg (ICSI), the epigenome of the fetus underwent stronger changes than with standard IVF, in which the sperm themselves fertilize the egg in a test tube.

"The biological role of epigenetic changes in germ cells is still unclear, but it seems that mammals transmit different information to the next generation in this way, depending on the age of the parents. If we understand how the epigenome of spermatozoa is formed and how it determines the health of offspring, we will be able to influence the health of the child even before conception," says Oleg Sergeev, Ph.D., Senior researcher at the Belozersky Research Institute of the Moscow State University, head of the project supported by the RNF grant.

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