The Naked Mole-Rat: Beauty in the Beast
Upon hearing the words “naked mole-rat” some people experience relief knowing that they could never be so ugly. Others likely feel jealousy, knowing these animals achieve an extraordinary lifespan of more than 31 years without succumbing to many of the dysfunctions we commonly associate with aging. I sympathize with you if you’re an individual who’s green-eyed with envy at these critters, since aging is a major risk factor for many diseases, including cardiovascular disease – the number one killer of humans. Given this and the naked mole-rat’s longevity, my mentor, Dr. Rochelle Buffenstein, thought that this rodent might provide beneficial new insights into cardiovascular aging.
However, prior to my joining Dr. Buffenstein’s lab at the Barshop Institute in 2010, the only information we had about the naked mole-rat heart came from a paper in 1951 describing the species’ cardiac anatomy. Figuring out the species heart rate
was the first small step in filling this research void. Naked mole-rats have a very low heart rate of about 250 bpm. For a rodent of their size, it should be around 500-600 bpm1. The other facets of their cardiac function follow suit: depressed cardiac output and blood pressure, as well as cardiac contractility so low that it would border on a diagnosis of systolic heart failure in humans. Yet, when you stimulate naked mole-rats under exercise conditions, they display a more than two-fold increase
in their cardiac function. This is much greater than that achieved by a laboratory mouse stimulated under the same conditions. Such a large cardiac reserve is right in line with their overall physiology. The species has a low basal metabolic rate that can increase more than five-fold when these rodents are furiously excavating their subterranean burrows in the wild. It appears that the naked mole-rat heart is equivalent to a car engine that spends most its time idling on low, saving fuel, but can accelerate very well when it needs to. After characterizing the naked mole-rat heart, the question of how these animals’ hearts perform over the course of their lengthy lifespans still remained.
It’s well-known that mammals – including monkeys, dogs, mice, and humans – share various hallmarks of cardiovascular aging. You are probably well aware of a few of these. As we and other mammals age, systolic blood pressure increases, arteries stiffen, and there is a decline in the heart’s maximum function during exercise. The heart also undergoes structural changes – even in the absence of overt cardiovascular disease – that cause a decrease in the heart’s diastolic, or relaxation, capabilities. We wanted to see how the naked mole-rat stacked up against other species.
It turns out that none of the signs of cardiovascular aging, save for cardiac fibrosis, are present in naked mole-rats until 24 years of age.2 In human years, this would be equivalent to a person being free of cardiovascular declines until after the age of 90! You and I can expect to suffer cardiac functional declines by mid-age. The one age-related change we did find was increased collagen deposition, leading to hindered relaxation capabilities and diastolic function. However, this change in the naked mole-rat is largely attenuated in comparison to the declines that we or other mammals experience. Consequently, the aging naked mole-rat heart is unique among those of mammals.
We’re now moving on to finding out what the naked mole-rat is doing to delay or attenuate age-related cardiovascular declines. All signs point to their cardiovascular aging profile stemming from their evolved adaptions to a natural subterranean habitat and subsequent stress resistance. Maybe if we decided to take up residence underground and grew large teeth all our cardiovascular aging problems could be solved. But prior to undergoing some very costly relocation and orthodontic procedures, we’re hoping that gaining more insights from the naked mole-rat will help us better understand how to age successfully and maintain youthful cardiovascular health.
Kelly Grimes is currently a Ph.D. student in the laboratory of Dr. Buffenstein in the Physiology & Pharmacology Discipline. She has currently published four papers towards her degree.
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