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Looking for the Differences that Make Naked Mole Rats Long-Lived

Naked mole rats are of interest to researchers because they can live nine times as long as comparable rodent species: this implies that they are a good place to look for determinants of longevity and important mechanisms of aging. You can go far in biology by comparing similar species that nonetheless exhibit sharply defined differences in your area of interest. The naked mole rat genome was sequenced and published this year, but research into the genetics of aging in the species that predates the availability of the full genome is still arriving at the presses. For example, there is this open access paper:

RNA Sequencing Reveals Differential Expression of Mitochondrial and Oxidation Reduction Genes in the Long-Lived Naked Mole-Rat When Compared to Mice

The naked mole-rat is not only the longest-lived rodent, but has a much longer lifespan than expected for its relatively small body size and has been shown to be extremely resistant to neoplasia. Furthermore, since a number of other rodents including mice, rats and guinea pigs already have had their genome sequenced, the naked mole-rat is a prime candidate for comparative genomics studies. ... Using a combination of 2nd-generation sequencing platforms, [we] were able to compare gene expression between wild-derived mice and naked mole-rats without using a naked mole-rat reference genome.

Gene expression is the process by which proteins are produced from the DNA blueprint. How much of any given protein is produced at any given time, and how that changes over time and in response to circumstances, is at least as important as what the protein is. Examining different levels of protein production between neighboring species is a good way to narrow down the biological mechanisms that explain their differences. In this case:

Within over-expressed genes in the naked mole-rat, genes associated with oxidoreduction were strongly overrepresented as well as genes associated with mitochondria and more specifically mitochondrial matrix. Consistent with the free radical theory of ageing, the over-expression of genes related to oxidoreduction could protect the naked mole-rat from reactive oxygen species. [With caveats, and] in view of the hypothesis that mitochondria play a major role in mammalian ageing, these results point towards a putative role for oxidoreduction and mitochondrial alterations in the long lifespan of the naked mole-rat.

You might compare this view with the membrane pacemaker hypothesis, that has naked mole rat longevity stemming from the fact that vulnerable cell components such as mitochondria are have a composition that renders them resistant to damage caused by free radicals, the reactive byproducts of cellular-fuel-generation taking place within mitochondria. The mitochondria themselves are the first target for those free radicals, and if you look back in the Fight Aging! archives, you'll find an explanation as to how damage to mitochondria can spiral into damage throughout the body - and hence aging.

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