Slow Aging: Insights from an Exceptionally Long-Lived Rodent, the Naked Mole-Rat

Abstract

As organisms age, one commonly notes a decline in vitality, fertility, and function with a concomitant increase in mortality risk. In short-lived animals, this decline is rapid, reflecting poor defense against aging. On the other hand, long-living organisms may show markedly attenuated rates of aging. Investigating how this is achieved may elucidate key mechanisms employed in slow or successful aging, characteristics we are interested in better understanding and even emulating. One such extraordinarily long-lived organism is the naked mole-rat. Naked mole-rats live in captivity an order of magnitude longer than similar-sized mice (>30 years). The common cause of death is still unknown and to date cancer has not been observed in these long-living rodents. Unlike the situation with most mammals, females continue to breed throughout their long lives and exhibit no decline in fertility well into their third decade. Only slight age-related changes are observed in all biochemical, physiological, and morphological characteristics studied to date. Clearly, these endogenous processes have evolved to dramatically extend healthy life span in this species, and typical age-associated acceleration in mortality risk that characterizes other mammalian species is attenuated. Studies addressing mechanisms of aging in this species have yielded surprising data: Naked mole-rat reproductive profiles are not typical of slow-aging K-selected animals and do not support the disposable soma theory of aging; short telomeres and low levels of telomerase in somatic tissue are in conflict with the telomere theory of aging; and high levels of oxidative damage diverge from those expected from the oxidative stress theory of aging. The challenge that lies ahead is to determine the mechanisms that facilitate the unusual profile associated with slow aging and prolonged health span in this rodent, and to test the ubiquity of these mechanisms in other species. As such, the naked mole-rat will prove to be an important animal model with which to address successful aging.