The exceptional longevity of the naked mole‐rat may be explained by mitochondrial antioxidant defenses

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12916

Daniel Munro, Cécile Baldy, Matthew E. Pamenter, Jason R. Treberg

TWO THEORIES OF AGEING

The oxidative damage theory of ageing postulates that  a slow and steady accumulation of oxidative damage to macromolecules, which increases with age, causes the decline of physiologic functions. The oxidative damage is caused by reactive oxygen species (ROS) of mitochondrial origin.

The mitochondrial oxidative stress hypothesis states that ageing is primarily driven by loss of mitochondrial function with time, caused by oxidative stress. This theory stems from the fact that ROS are mostly released inside mitochondria, therefore directly exposing them to damage.

THE PRESENT STUDY

Naked mole-rat (NMR) can live >30 years in lab conditions, with a very long healthy lifespan, in comparison to <4 years for mice. Studies have shown that NMRs are subject to extensive oxidative damage (evidence found in liver cells) and high ROS productions, as much as mice. Therefore, their longevity has been widely used to contradict the oxidative damage theory of ageing. The mitochondrial oxidative stress hypothesis cannot explain these observations.

The authors, writing in Aging Cell, showed that NMRs mitochondria are much more efficient than mice's in consuming ROS. They also find evidence that skeletal muscle and heart mitochondria of mice and NMRs produce similar quantities of ROS.  Therefore, the authors conclude that the marked difference in longevity between the two species is to be attributed to the much greater capacity of NMRs mitochondria to clean ROS.

This finding supports the mitochondrial oxidative stress hypothesis, without positing that NMRs mitochondria produce less ROS. Further research could tell whether other long-lived species share this greater mitochondrial detoxifying capacity.