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The Naked Mole Rat's Secret to Anti-Aging

Our gnarly, cold-blooded mammalian friends offer a novel way of clearing out junk proteins from cells.
Image: Roman Klementschitz/Wiki

Naked mole rats have it all figured out. Not only are they among the most well-adapted, finely-tuned creatures on Earth, they've also figured out (in an evolutionary sense) how to ditch aging. Or, rather, naked mole rats have figured out how to ditch one of aging's central mechanisms, the steady accumulation of junk protein material that grows and festers in the body like the rising tide of bags and stench following a New York City garbage strike.

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Our naked mole rat friends have devised a way of disposing of all of that uncollected waste, with the effect of vastly longer lives, at least relative to other rodents. This is according to a new study in the journal BBA: Molecular Basis of Disease describing a cellular factor that guards and guides the activity of the protein complex proteasome, whose job involves the chemical breaking down of leftover proteins. Proteasome is the garbage collector, the garbage truck, and the incinerator, in other words.

Proteins are a fundamental cellular currency, mediating communication among cells, acting as immune system agents, providing structural building materials, and sometimes serving as food/energy sources. Imagine if every word you've ever spoken, every thought you've exchanged with someone else, was really made up of a blob of biological gunk. And as you communicate more and more that gunk just accumulates around you, every thought falling as a wet splat onto the quickly mounting pile.

Or imagine the stacks of old mail in a hoarder's apartment, slowly accumulating and making it harder and harder for the resident to get around that apartment and do the stuff they need to do in order to function normally and, well, survive. Things in that apartment-cell just get slower and more confused as time goes on. This apartment-cell might be part of the nucleus pulpous material at the center of the human spinal cord. As the protein hoarding phenomenon progresses in not just that single apartment-cell but all the ones surrounding it, the pulpous slowly turns a brownish shade, drying as sulfurous materials collect. A 2002 study estimated that cellular junk proteins increase at a rate of about 1 percent per year.

The life expectancy of the naked mole rate is 31 years, roughly equal to the average human life expectancy at the beginning of the 20th century. This longevity traces back in part to exceptionally robust proteasome proteins in the naked mole rats that are uniquely able to survive a progressive onslaught of proteasome poisons. This resistance is enabled by a particular "transferable chaperone-containing cytosolic factor." This factor basically hangs out with the proteasomes, acting to modulate the garbage collector protein's activity. The proteasomes remain active in the factor's presence, and are moreover pushed to increase production of peptidase materials, enzymes that work to break the chemical bonds in certain proteins. It'd be sort of like taking a mulcher to our hoarder example's junk mail.

The robustness of our mole rat friends goes a bit beyond the above, however, and includes rather bizarre adaptations like an inability to feel pain on their skin, "cold blood," exceptionally low rates of metabolism and respiration, an impressive talent for backwards scurrying, and teeth better suited to digging through dirt than normal teeth functions. They live off a combination of their own feces and large tubers (roots) found deep underground. It's tempting to call the species overadapted—imagine a naked mole rat in even just a slightly different environment—but it's safe to say Earth won't run out of suitable dirt anytime soon either.

The good news is that the anti-aging factor used by mole rats is portable. In science-speak, "Moreover, mouse, human, and yeast proteasomes exposed to the proteasome-depleted, naked mole-rat cytosolic fractions, recapitulate the observed inhibition resistance, and mammalian proteasomes also show increased activity," the paper explains. Maybe it's time to look at our rat-worm friends for promises of immortality (or at least much longer lives) rather than Ray Kurzweil and his Singularity.