There have long been good reasons to suspect that an individual’s DNA shapes how they age and how long they live. But “it’s always been iffy as to whether there’s true genetic control of lifespan and longevity”, says Robert Williams, a geneticist at the University of Tennessee Health Science Center in Memphis.
Now, in a study that looked at more than 3,200 genetically diverse mice, Williams and his colleagues have identified several parts of the genome that influence longevity. Some of these genetic effects differed between male and female mice — and some affected lifespan only in mice that reached a certain age.
Longevity is a complex trait, and the study has done well to uncover firm genetic links, says João Pedro Magalhães, a geneticist at the University of Birmingham, UK. But the work poses many questions. “It’s a stepping stone,” he says, “towards understanding the genetics of longevity, and ultimately mechanisms.”
The study, published in Science on 29 September1, found that one part of chromosome 12 influenced longevity across all mice. But female life expectancy was also influenced by a region of chromosome 3. (Mice have 20 pairs of chromosomes.)
In males, the story was more complicated. Many male mice die young — probably because of the stress of male–male social interactions. Only after the authors had excluded these young deaths from their analysis did they find five chromosomal regions that influenced life expectancy in male mice that had lived to greater ages.
The chromosomal regions the researchers identified are large. “Right now, our loci are pretty fat — 100-plus genes per locus,” says Williams, so it is not yet clear exactly which genes underlie the longevity effects.
And it is uncertain what processes these gene variants are affecting, says Maroun Bou Sleiman, a geneticist at the Swiss Federal Institute of Technology in Lausanne who co-led the study. “The question that remains is, are these ageing genes that are determining longevity?” Genes could also prolong life by protecting against specific diseases, such as cancer. Finding true ageing genes, says Bou Sleiman, might allow researchers to develop interventions that keep people healthy for longer.
The researchers also looked at the mechanisms through which longevity genes might act, and found a compelling link between lifespan and growth rate. Mice born as part of a small litter are known to die younger, because they grow faster in the womb. The team found that one mouse chromosomal region that shapes life expectancy might be linked to growth rates.
Then the group used data from the UK Biobank to show that in humans, people who grow faster in childhood also have shorter lifespans, probably because they go on to have a higher body-mass index in adulthood. Together, the findings support the idea that early growth rates affect longevity.
“If you want to study ageing or longevity, keep an eye on life history,” says Bou Sleiman.