Genome sequencing reveals insights into physiology and longevity of the naked mole rat

The naked mole rat (NMR, Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal(1). Although the size of a mouse, its maximum lifespan exceeds 30 years and makes this animal the longest living rodent. NMRs show negligible senescence, no age-related increase in mortality, and high fecundity until death(2). In addition to delayed aging, NMRs are resistant to both spontaneous cancer and experimentally induced tumorigenesis(3,4). NMRs pose a challenge to the theories that link aging, cancer and redox homeostasis. Although characterized by significant oxidative stress(5), the NMR proteome does not show age-related susceptibility to oxidative damage nor increased ubiquitination(6). NMRs naturally reside in large colonies with a single breeding female, the “queen,” who suppresses the sexual maturity of her subordinates(11). NMRs also live in full darkness, at low oxygen and high carbon dioxide concentrations(7), and are unable to sustain thermogenesis(8) nor feel certain types of pain(9,10). Here we report sequencing and analysis of the NMR genome, which revealed unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness, altered visual function, circadian rhythms and taste sensing, and insensitivity to low oxygen. This information provides insights into NMR’s exceptional longevity and capabilities to live in hostile conditions, in the dark and at low oxygen. The extreme traits of NMR, together with the reported genome and transcriptome information, offer unprecedented opportunities for understanding aging and advancing many other areas of biological and biomedical research.