Evolutionary transcriptomics shows that longevity in mammals is largely driven by polygenic selection and indirect selection
Mammals have a lifespan that is 100 times greater than the average. This natural experiment may reveal the evolutionary forces and cellular features that determine longevity. We conducted a transcriptomics comparison of liver, brain, and kidney tissues from 106 mammalian species to understand the relationship between gene variation and maximum life expectancy. In all three organs, we found that the expression was largely conserved. Very few genes showed a common pattern of expression with longevity. Many pathways, such as the \”Insulin Signaling Pathway\” and the \”FoxO Signaling Pathway\”, have accumulated correlations to maximum lifespan in mammals. Analysis of selection features reveals that genes associated with methionine restriction, whose expressions are linked to longevity, are strongly selected in long-lived mammal species. This suggests that natural selection as well as artificial intervention could use a similar approach to control lifespan. These results indicate that the natural regulation of lifespan via gene expression may be driven by indirect selection and polygenic models.
The authors have not declared any competing interests.