University of Utah: Could Slowing the Rate of DNA Mutations Be the Key to the Elusive Fountain of Youth

Our cells mutate in the course of our lives despite our DNA repair mechanisms. According to recent research, an individual with a high mutation rate can live up to five years less than an individual with fewer mutations. In women, fertility is also linked to this mechanism.The Connection Between Heredity And Longevity

The faster our DNA is damaged, the more life expectancy and, for women, fertility, can be altered. For example, a high rate of mutation accumulation could lead to a five-year reduction in life expectancy compared to those who are mostly spared from mutations, according to research published in the journal Scientific Report. Although some of the factors driving this mutation rate are genetic, many are fortunately related to our environment and lifestyle, which calls for smoking bans, healthy eating, and physical activity.

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Mutations accumulate in our cells over the course of life

Our cells mutate in the course of our lives. Each time they divide in order to renew themselves, they have to duplicate their long DNA molecule, which contains all the genetic information that defines them. But copying means the risk of error, that is, mutation. Although in the worst case, these accumulated mutations can give the cells carcinogenic properties, their mere presence is an important indicator of the effectiveness of DNA repair mechanisms that would have been poorly copied. This process is present in all our cells, whether they are germinal cells (reproductive: eggs and spermatozoa) or somatic cells (others).

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Researchers at the University of Utah have hypothesized that the rate of mutations that persist and vary from person to person despite the control of DNA repair systems is predictive of life expectancy (the somatic cell side) and, in women, of fertility (the germ cell side). Indeed, it is known that these mechanisms become less efficient with age and that mutations can accumulate. As far as fertility is concerned, previous work has shown that women who have had their last child after 40 years live much longer than women who have had their last child at a younger age. Furthermore, reaching natural menopause much later in life is associated with a higher life expectancy.

Life expectancy and fertility prediction based on the mutation rate

The team thus sequenced the DNA of 61 men and 61 women who were grandparents in 41 different families whose samples were taken between the 1980s and 2000. By comparing the mutations found in their DNA with those of their children, the researchers were able to deduce which mutations had been transmitted by the parents (germ cell mutations) and which mutations were specific to them (somatic cell mutations). This enabled them to compare each parent of the first generation with other parents of the same sex and estimate their aging rate. “Compared to a 32-year-old man with 75 mutations, a 40-year-old man with the same number of mutations would be expected to age more slowly,” said Richard Cawthon, who led this work, in a press release. “He would be expected to die later than the 32-year-old man.

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Five years of additional life expectancy

This is indeed what the research team has determined. From puberty onwards, mutations accelerate, suggesting that aging begins in adolescence. DNA damage rates can then vary from individual to individual, “both due to inherited genetic factors and differences in environmental stress, including diet, exercise, other lifestyles and basic socio-economic factors (income and wealth, education and occupation),” researchers list.

After adapting to age, researchers found that people with the slowest rates of mutations accumulation are likely to live about five years longer than those who have accumulated mutations more rapidly. This difference is comparable to the effects of smoking or lack of physical activity, Cawthon says.

More mutations potentially mean less fertility for women

As puberty is apparently the starting point for accelerated mutation, a later onset of menstruation is associated with a longer life expectancy, a reduced risk of cancer, and a late menopause, the authors conclude. Women with the highest mutation rates were more likely to be younger when their last child was born. This suggests that the high mutation rate affected their fertility.

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A second shot at Youth

“The ability to determine when aging begins, how long women can remain fertile, and how long people can live is an exciting opportunity,” says Richard Cawthon. “When we reach a point where we can better understand what kind of developmental biology affecting mutation rates occurs during puberty, we should be able to develop medical interventions to restore DNA repair and other mechanisms to what they were before puberty. If we could do this, it would be possible for people to live much longer and stay healthy. Pharmaceutical and lifestyle interventions could possibly one day reprogram or reactivate the genes that maintain DNA stability and give us a second youth.

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References

Germline mutation rates in young adults predict longevity and reproductive lifespan

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