Predicting Lifespan with Mutation Rate

Differences in the rate that genetic mutations accumulate in healthy young adults could help predict remaining lifespan as well as remaining years of fertility in women, according to University of Utah Health scientists. The study, published today in Scientific Reports, found that young adults who acquired fewer mutations over time lived about five years longer than those who acquired them more rapidly.

Scientists have long known that DNA damage constantly occurs in the body. Because of this, there are various mechanisms in place that repair this damage and prevent potentially harmful mutations. But as we age, these mechanisms become less efficient, and more mutations accumulate.

The researchers analyzed DNA sequences in trios consisting of pairs of grandparents and one of their children. Mutations found in the child’s blood DNA that were not present in either parent’s blood DNA were then inferred to have originated in the parents’ germlines. The researchers were then able to determine which parent each germline mutation came from, and, therefore, the number of such mutations each parent had accumulated in egg or sperm by the time of conception of the child.

Next, the researchers compared each parent to others of the same sex and estimated their rate of aging. “So, 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 aging more slowly,” says first author Richard Cawthon.

Some young adults acquired mutations at up to three times the rate of others. After adjusting for age, the researchers determined that individuals with the slowest rates of mutation accumulation were likely to live about five years longer than those who accumulated mutations more rapidly—a difference comparable to the effects of smoking or lack of physical activity.

Women with the highest mutation rates had significantly fewer live births than other women and were more likely to be younger when they gave birth to their last child. This suggests that the high rate of mutation also affects fertility.

“The ability to determine when aging starts, how long women can stay fertile, and how long people can live is an exciting possibility,” Cawthon says. “If we can get to a point where we better understand what sort of developmental biology affecting mutation rates is happening during puberty, then we should be able to develop medical interventions to restore DNA repair and other homeostatic mechanisms back to what they were before puberty. If we could do that, it’s possible people could live and stay healthy much longer.”