A universal limit for mammalian lifespan revealed by epigenetic entropy

Age-associated DNA methylation patterns have shown strong associations with species lifespan. However, it remains unclear whether epigenetic noise levels can account for the observed differences between mammalian species. In this study, we examined the rate of loss of epigenetic information with age by measuring entropy at mammalian conserved CpG sites across a diverse range of species. Longer-lived mammals tend to gain fewer noisy CpGs with age, irrespective of whether these originate from hyper- or hypomethylation processes. Importantly, we found that the rate of epigenetic entropy gain declines in a linear fashion with species maximum lifespan, pointing to the existence of a universal limit for mammalian lifespan in the vicinity of 220 years.