Scientists have sequenced the genome of the naked mole rat, a highly social underground rodent of extraordinary longevity that retains youthful biology, good health and fertility well into its final years. The naked mole rat lives ten times longer than its distant cousins the rat and the mouse, and the hope is that by comparing their genomes, scientists will unlock some of the genetic and biological secrets of aging and cancer, including in humans.
A large team of international researchers, including members of the University of Texas (UT) Health Science Center at San Antonio in the US, where there is a colony of more than 2,000 naked mole rats, worked on the study, which was published in Nature on 12 October.
Co-author Dr Rochelle Buffenstein, professor of physiology at the Barshop Institute for Longevity and Aging Studies, part of the UT Health Science Center San Antonio, told the media that aging and biomedical research could learn a lot from the naked mole rat ‘s capacity to resist cancer and maintain protein integrity in the face of oxidative damage.
“If we understand which genes are different or are expressed differently in naked mole rats — compared to short-lived mice that clearly have poor defenses against aging and cancer — we might find clues as to why the naked mole rat is able to extend both health span and longevity, as well as fight cancer, and this information could be directly relevant and translatable to humans.”
The naked mole rat (Heterocephalus glaber) lives for up to 31 years in captivity, the longest lifespan of any known rodent, including lab rodents. Resembling a pink “sabre-toothed sausage”, the naked mole rat is about the same size as a mouse and is remarkably tolerant of low oxygen and high levels of carbon dioxide.
Scientists are very interested in its biology because it shows little signs of aging (“negligible senescence”), no age-related increase in mortality, and remains highly fertile until death. As well as delayed aging, the naked mole rat is resistant to both spontaneous cancer and experimentally induced tumor formation, it can’t feel certain types of pain and is able to rewire its brain (high neural plasticity).
Moreover, unusual for a mammal, its body temperature is largely dependent on the temperature of its environment (poikilothermy); in this respect it is more like a reptile or an amphibian.
In the wild, naked mole rats live underground in full darkness in large family groups. Another unusual feature of this remarkable mammal is its reproductive behavior which is more like that of bees and termites in that each group has only one breeding female, “the queen”, who suppresses the sexual maturity of lower ranking females.
When they deciphered the animal’s genome, the researchers found:
“… unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing.”
“The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research,” they concluded.
Buffenstein described the animal’s genetic blueprint as a “treasure trove” for many areas of biology and medicine that will help scientists find out more about longevity, cancer resistance and pain tolerance, as well as how to live in a low-oxygen environment.
“Understanding their genomic footprint may reveal how they are able to maintain the integrity of their proteins and DNA far better than other animals do in old age, as well as how they mitigate the translation of oxidative damage into age-related declines and disease,” she added.
The National Institute on Aging, the Glenn Foundation for Medical Research, the Ellison Medical Foundation and the American Federation for Aging Research helped pay for the research.
Written by Catharine Paddock PhD