Scientists discover «molecular clocks» of aging in sperm

What the scientists discovered

Scientists have described a previously unnoticed mechanism of age-related changes in male reproductive cells: as males age, not only the DNA but also the RNA molecules in sperm change. ScienceAlert reports the discovery, citing a study published in The EMBO Journal; Life.ru also covered it. The finding concerns small non-coding RNAs contained in sperm that participate in the regulation of cellular processes. The analysis used PANDORA-seq technology, which makes it possible to detect RNA varieties that are poorly captured by conventional sequencing.

A jump in mice and gradual changes in humans

In old mice, the number of long fragments of ribosomal RNA in the sperm heads increased, while short fragments became fewer. Moreover, the restructuring was uneven: a pronounced jump was observed in mid-life of the animals. In humans the picture is different: an analysis of sperm samples from two independent groups of donors confirmed a link between the ratio of long and short RNA fragments and the men's age, but an equally sharp age-related turning point has not yet been identified. «This is like discovering a molecular clock that ticks with age in both mice and humans,» explained Qi Chen, a researcher at the University of Utah. According to him, the changes may accumulate gradually before reaching a critical level.

Possible consequences and limitations

To assess possible effects, the scientists introduced into mouse embryonic stem cells a combination of RNA fragments characteristic of the sperm of old animals and recorded changes in the activity of genes associated with metabolism and neurodegenerative processes. This suggests that the father's age may influence early embryonic development not only through the accumulation of DNA mutations: sperm also pass RNA molecules to the egg that may potentially be involved in regulating the genes of the future organism. Importantly, the study does not yet prove that the detected changes directly cause infertility or diseases in children: the authors still have to establish the causes of the RNA restructuring and verify its consequences for human reproductive health. In the future, the discovery may help create ways to assess the biological age of sperm and sperm quality.

Context of previous work

The new study adds to earlier data on the «male» factor of age. As Life.ru reported, scientists previously discovered the accumulation of dangerous genetic mutations in sperm with age: having analyzed the DNA of more than a thousand sperm from 81 men aged 24 to 75, the researchers found that in mature men certain mutations occur more often, which potentially increases risks for offspring. At the same time, as noted in that publication, the presence of genetic changes does not mean they will necessarily be passed on to a child. The difference of the new work is that it points to another channel of age-related influence — RNA — but also leaves more open questions: in humans, the «jump» clearly visible in mice has not yet been confirmed.