DNA methylation clocks tick in naked mole rats but queens age more slowly than nonbreeders

Steve Horvath(University of California, Los Angeles), Amin Haghani(University of California, Los Angeles), Nicholas Macoretta(University of Rochester), Julia Ablaeva(University of Rochester), Joseph A. Zoller(University of California, Los Angeles), Caesar Z. Li(University of California, Los Angeles), Joshua Zhang(University of California, Los Angeles), Masaki Takasugi(University of Rochester), Yang Zhao(University of Rochester), Elena Rydkina(University of Rochester), Zhihui Zhang(University of Rochester), Stephan Emmrich(University of Rochester), Ken Raj(Public Health England), Andrei Seluanov(Sivas State Hospital), Chris G. Faulkes(Queen Mary University of London), Vera Gorbunova(Sivas State Hospital)
Nature Aging
December 23, 2021
10.1038/s43587-021-00152-1
Cited by 110Open Access
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Abstract

Abstract Naked mole rats (NMRs) live an exceptionally long life, appear not to exhibit age-related decline in physiological capacity and are resistant to age-related diseases. However, it has been unknown whether NMRs also evade aging according to a primary hallmark of aging: epigenetic changes. To address this question, we profiled n = 385 samples from 11 tissue types at loci that are highly conserved between mammalian species using a custom array (HorvathMammalMethylChip40). We observed strong epigenetic aging effects and developed seven highly accurate epigenetic clocks for several tissues (pan-tissue, blood, kidney, liver, skin clocks) and two dual-species (human–NMR) clocks. The skin clock correctly estimated induced pluripotent stem cells derived from NMR fibroblasts to be of prenatal age. The NMR epigenetic clocks revealed that breeding NMR queens age more slowly than nonbreeders, a feature that is also observed in some eusocial insects. Our results show that despite a phenotype of negligible senescence, the NMR ages epigenetically.

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