Genetic mutation rate could predict lifespan and fertility

Determining when ageing starts, our predicted remaining lifespan, and how long women remain fertile can be predicted from the rate we accumulate mutations as young adults, scientists claim.

Geneticists have long known that the efficiency at which we repair our DNA declines as we grow older, meaning we accumulate mutations over time. Researchers based at the University of Utah, have shown the rate this occurs can act as a useful biomarker, which they hope will lead to the development of interventions aimed at slowing the ageing process.

'If the results from this small study are validated by other independent research, it would have tremendous implications,' said Professor Lynn B Jorde, chair of the Department of Human Genetics at University of Utah and co-author.

Their study, published in Nature Scientific Reports, sequenced the DNA from 41 three-generation Utah families to measure the accumulation of germline mutations. This refers to mutations that occur in the sperm or the egg (germ cells), which are not found in any other parental cells but can be passed onto the offspring.

By detecting mutations in the DNA of children that were not present in their parents', they were able to identify mutations that could then be traced to the germline of either their mother or their father. This meant they could infer the number of mutations each parent had accumulated in their sperm or egg by the time of conception.

The authors showed these mutation rates could provide a measure of 'reproductive and systemic ageing', since they were associated with duration of childbearing in women as well as lifespan in both sexes.

Some individuals accumulated mutations up to three times slower than others and lived up to five years longer as a result – a difference similar to the effects of smoking or lack of physical activity. 'Compared to a 32-year-old man with 75 mutations, we would expect a 40-year-old with the same number of mutations to be ageing more slowly,' explains Dr Richard Cawthon, associate professor at the Department of Human Genetics at the University of Utah and lead author of the study. 'We’d expect him to die at an older age than the age at which the 32-year-old dies.'

Similarly, women with the lowest mutation rates had significantly more live births, and were more likely to be older when they gave birth to their last child, suggesting these mutation rates impact fertility too.

Consistent with previous reports, the scientists also found that mutations began to occur at an accelerating rate soon after puberty, meaning we start to age in our teens. Dr Cawthon hopes that in the future we will 'be able to develop medical interventions to restore DNA repair and other homeostatic mechanisms back to what they were before puberty', which could lower the risk of ageing-related diseases. 'If we could do that, it's possible people could live and stay healthy much longer' he explained.