The ultimate human lifespan? Mammals may share the same boat
Mammals have all kinds of lifespans ranging from six months to 200 years old. This is a fact that has often perplexed scientists around the world.
Now, researchers from the Wellcome Sanger Institute in Cambridge may have solved that mystery and the solution relates to the speed of genetic damage, according to a press release by the institution released Wednesday. Their work analyzed the genomes from 16 species of mammal (from mice to giraffes) and found that the longer the lifespan of a species, the slower the rate at which DNA mutations occur.
Slowing down the rate of DNA mutations
This means that the long-living animals are the ones capable of successfully slowing down their rate of DNA mutations regardless of their size.
“To find a similar pattern of genetic changes in animals as different from one another as a mouse and a tiger was surprising. But the most exciting aspect of the study has to be finding that lifespan is inversely proportional to the somatic mutation rate. This suggests that somatic mutations may play a role in ageing, although alternative explanations may be possible. Over the next few years, it will be fascinating to extend these studies into even more diverse species, such as insects or plants," said Dr Alex Cagan of the Wellcome Sanger Institute and co-author of the new study.
For comparison, mice undergo 796 mutations a year resulting in short lives of 3.7 years while the average human undergoes only 47 mutations resulting in a lifespan of 83.6 years. The researchers further reviewed the genetic errors in the species' stem cells and found that the average number of mutations at the end of a lifespan across species was around 3,200.
The result of multiple forms of molecular damage
“Ageing is a complex process, the result of multiple forms of molecular damage in our cells and tissues. Somatic mutations have been speculated to contribute to ageing since the 1950s, but studying them had remained difficult. With the recent advances in DNA sequencing technologies, we can finally investigate the roles that somatic mutations play in ageing and in multiple diseases. That this diverse range of mammals ends their lives with a similar number of mutations in their cells is an exciting and intriguing discovery," said Dr Inigo Martincorena, the senior author of the study.
The study was published in the journal Nature.
The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans. Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found that somatic mutagenesis was dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans8, although the relative contribution of each signature varied across species. Notably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied showing a comparable association. Despite widely different life histories among the species we examined—including variation of around 30-fold in lifespan and around 40,000-fold in body mass—the somatic mutation burden at the end of lifespan varied only by a factor of around 3. These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing.