Epigenetic aging of the demographically non-aging naked mole-rat [RRBS]

The naked mole-rat (NMR) is an exceptionally long-lived rodent that does not show increased mortality with age, uniquely defining NMR as a demographically non-aging mammal. Here, we performed bisulfite sequencing on over one hundred NMR blood samples differing in age, assessing more than 3 million common CpG sites. We observed an information loss of the NMR methylome during aging suggesting that NMR ages. Unsupervised clustering based on the 758 CpG sites whose methylation level strongly correlate with age suggests an age-related shift of the NMR methylome. We also developed an epigenetic aging clock that accurately predicts the NMR age spread across the genome. Based on the clock, NMRs age much slower than mice and much faster than humans, consistent with their known maximum lifespans. We further found that patterns of age-related methylation changes of aging clock sites in Tert and Prpf19 showed differences between NMRs and mice. Together, the data indicate that NMRs, like other mammals, epigenetically age even in the absence of demographic aging of this species. Examination of DNA methylation (RRBS) of naked mole-rat blood samples ranging in age from 0.01 years to 11.63 years.