Why Naked Mole-Rats Have High Oxidative Damage but Live a Long Life: A Simple Explanation Based on the Oxidative Stress Theory of Aging

Abstract

Compared to mice with the same body mass, naked mole-rats have a lower metabolic rate, higher homeostasis-maintaining activities, higher oxidative damage levels, but a longer lifespan. These observations have raised serious challenges to the widely accepted oxidative stress theory of aging, which suggests a negative correlation between damage levels and lifespan. Here, we introduce a simple theoretical model based on energy conservation and the oxidative stress theory. Employing the model and the physiological parameters of mice and naked mole-rats, we explain why naked mole-rats have higher damage levels despite their higher somatic maintenance efforts; why damage levels in naked mole-rats seem not to change over age; and how these factors concertedly result in a longer lifespan in naked mole-rats. Our results highlight the energy tradeoff between biosynthesis and somatic maintenance, and suggest that the rate of damage accumulation over age and the existence of a threshold of damage for death are the keys to solve the paradox raised by naked mole-rats.