Demographic Aging is Absent in Naked Mole Rats

Naked mole rats are an extreme example of compression of morbidity in mammals, in that individuals show few signs of aging until very late in life. Their biochemistry is peculiar in a number of ways when compared with other mammals. Their senescent cells do little harm to surrounding tissues; their protein synthesis is highly efficient; the are better at repairing DNA damage; they exhibit impressive cancer suppression mechanisms; and so forth. Will it be possible to build human enhancements or medical technologies from what is learned of naked mole rat metabolism? It is plausible that this is a very complicated extremely long-term project; equally any part of naked mole rat biochemistry could turn out to inform a comparatively simple, targeted intervention. It is too early to say.

The species Heterocephalus glaber, commonly known as the naked mole-rat, is a eusocial mammal endemic to the arid and semi-arid regions of northeast Africa. In the wild, naked mole-rats live an almost completely subterranean lifestyle, in colonies of up to 295 animals (average size is 60 animals/colony) that cohabitate a network of tunnels that the mole-rats dig themselves with their large, ever-growing incisors. Naked mole-rats are notable for their extreme lifespans, living longer than any other documented rodent, with the longest previously-reported lifespan of 37 years and many animals living beyond 30 years. These values are notable in the context of this species' small body size due to the strong correlation across species between that value and mammalian lifespan: maximum lifespan potential (MLSP) increases by 16% for each doubling of average species body mass.

For most mammalian species, lifespan is limited by an exponential increase in the per-day risk of death (i.e. mortality hazard) with age in accord with a statistical distribution first defined by Gompertz based on human mortality. The increase in mortality hazard with age is referred to as "demographic aging". We have previously shown H. glaber to achieve its exceptional longevity through defiance of this trend, exhibiting near constant mortality hazard across the full spectrum of observed lifespans, with no hazard increase evident even many-fold beyond their expected MLSP. For naked mole-rats, the lack of demographic aging is accompanied by seemingly-indefinite maintenance of many physiological characteristics that typically change with age. Naked mole-rats are resistant to age-related diseases such as cancer, neurodegeneration, and cardiovascular disease and show signs of tissue regeneration and remodeling preventing the deterioration of age-associated physiological function.

Here, we re-visited the demographic analysis of our naked mole-rat collection, with husbandry data now extended by five years across an expanded set of animals. We found our original conclusions of naked mole-rat mortality hazard being age-independent to be reproduced, using either the total sum of all historical data or only those data collected after our previous study - the latter qualifying as a replication study.