Epigenetic aging of the demographically non-aging naked mole-rat

Csaba Kerepesi, Margarita V. Meer, Julia Ablaeva, Vince G. Amoroso, Sang-Goo Lee, Bohan Zhang, Maxim V. Gerashchenko, Alexandre Trapp, Sun Hee Yim, Ake T. Lu, Morgan E. Levine, Andrei Seluanov, Steve Horvath, Thomas J. Park, Vera Gorbunova and Vadim N. Gladyshev ()
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Csaba Kerepesi: Brigham and Women’s Hospital and Harvard Medical School
Margarita V. Meer: Brigham and Women’s Hospital and Harvard Medical School
Julia Ablaeva: University of Rochester
Vince G. Amoroso: Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago
Sang-Goo Lee: Brigham and Women’s Hospital and Harvard Medical School
Bohan Zhang: Brigham and Women’s Hospital and Harvard Medical School
Maxim V. Gerashchenko: Brigham and Women’s Hospital and Harvard Medical School
Alexandre Trapp: Brigham and Women’s Hospital and Harvard Medical School
Sun Hee Yim: Brigham and Women’s Hospital and Harvard Medical School
Ake T. Lu: David Geffen School of Medicine, University of California
Morgan E. Levine: Yale School of Medicine
Andrei Seluanov: University of Rochester
Steve Horvath: David Geffen School of Medicine, University of California
Thomas J. Park: Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago
Vera Gorbunova: University of Rochester
Vadim N. Gladyshev: Brigham and Women’s Hospital and Harvard Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract The naked mole-rat (NMR) is an exceptionally long-lived rodent that shows no increase of mortality with age, defining it as a demographically non-aging mammal. Here, we perform bisulfite sequencing of the blood of > 100 NMRs, assessing > 3 million common CpG sites. Unsupervised clustering based on sites whose methylation correlates with age reveals an age-related methylome remodeling, and we also observe a methylome information loss, suggesting that NMRs age. We develop an epigenetic aging clock that accurately predicts the NMR age. We show that these animals age much slower than mice and much faster than humans, consistent with their known maximum lifespans. Interestingly, patterns of age-related changes of clock sites in Tert and Prpf19 differ between NMRs and mice, but there are also sites conserved between the two species. Together, the data indicate that NMRs, like other mammals, epigenetically age even in the absence of demographic aging of this species.

Date: 2022
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DOI: 10.1038/s41467-022-27959-9

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