Naked mole-rats exhibit exceptional longevity in comparison to other rodent species. They can live nine times longer than similarly sized mice, for example. There are no doubt a sizable number of distinct mechanisms that contribute to this difference in species life span, and the existence of mammals with widely divergent life spans acts as a natural laboratory for researchers interested in better understanding aging. If one species lives a much longer life than another, then using their differences in order to identify the more important aspects of cellular metabolism in the matter of aging may well be a faster approach than other strategies that aim to reverse engineer the workings of aging. Thus research groups have been energetically investigating the biochemistry of naked mole-rats for many years now.

Naked mole-rats are exceptionally resistant to cancer, to the point at which for all of the populations maintained across the years in laboratories and zoos, only a few cases of cancer have ever been reported. Of late the ability of naked mole-rats to suppress cancerous mutations and cancerous cells has become one of the primary areas of study when it comes to their metabolic peculiarities. Avoiding death by cancer probably isn't one of the most important contributions to naked mole-rat longevity, however.

Instead, it seems likely that at least some of the major determinants of longevity relate to mitochondrial function and cellular resistance to oxidative damage. The horde of mitochondria in every cell act as power plants, but also as a source of oxidative molecules. These are generated as a byproduct of the energetic chemical reactions needed to package up the adenosine triphosphate (ATP) used as fuel for cellular processes. The presence of too many oxidative molecules are harmful to cells, and mitochondria themselves can be damaged by oxidative molecules in ways that contribute to aging. The situation is far from simple, however: oxidative molecules are used as signals for cellular maintenance, and thus small or brief increases are in fact beneficial. Further, antioxidant processes in mitochondria act to clean up much of the exhaust of new oxidative molecules. This is a complex, dynamic system of oxidants and reactions to oxidants that does not lend itself to easy predictions of outcomes.

The membrane pacemaker hypothesis suggests that the important factor in all of this, when considering differences between species, is the composition of cell membranes, particularly those of mitochondria. Different cell membrane lipids are more or less vulnerable to oxidative reactions and consequent functional damage. Species like naked mole-rats, with very high levels of all of the markers of oxidative stress, yet few to no apparent consequences, are perhaps a good argument for the membrane pacemaker way of looking at things. Equally, the research here makes a different argument - that this is all about the degree to which mitochondria can direct their own antioxidant processes to consume oxidizing molecules, and naked mole-rats are much better at this than mice. It is known that raising levels of mitochondrial antioxidants, either via gene therapy or by delivering artificial antioxidants that localize to mitochondria, appears to slow aging in a number of different species. The question, as always, is the size of any specific contribution to the overall outcome.

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