Naked Mole-Rat Skin Shows Fewer Signs of Aging

Naked mole-rats exhibit a maximum life span that is many times longer than is the case for similarly sized mammals. Further, they are negligibly senescent, showing few age-related declines in function across much of that lengthy life span. That includes maintenance of stem cell populations and regenerative capacity, as well as a near immunity to cancer. Accordingly, the research community is very interested in uncovering the genetic and biochemical differences that allow naked mole-rats to achieve these desirable outcomes.

In today's open access paper, the authors report on their investigation of the biochemistry and aging of naked mole-rat skin. The skin in this species, like other organs, shows few signs of degenerative aging in comparison to other mammals. The maintenance of stem cell populations may be one of the more important aspects of this resilience to aging, but there are a few other surprises. Clearly some gene expression in the skin is changing in the latter half of life, but that does not appear to greatly impact the more important functions.

It is interesting to speculate as to how it is that gene expression can change while function remains youthful. What is actually changing under the hood? For example, it is known that naked mole-rats do accumulate senescent cells with age, but those senescent cells do not exhibit the harmful behavior found in other mammals. Further, naked mole-rats show signs of oxidative damage to cells with age, but that damage doesn't appear to produce the consequences observed in other mammals.

Single-cell transcriptomics reveals age-resistant maintenance of cell identities, stem cell compartments and differentiation trajectories in long-lived naked mole-rats skin

Constantly exposed to both internal and environmental stresses such as UV radiation or air pollutants, the skin ages and undergo profound changes in its appearance and functions. Indeed, aged skin undergoes gradual structural and functional degeneration, leading to thinning of epidermal and dermal layers, loss of elasticity, wrinkling, and dryness. These changes are responsible for delayed wounding, more frequent infections, pruritus, enhanced allergen/irritant penetrations with variable degree of dermatitis and eventually carcinogenesis. In rodents and humans, these phenomena have been partially attributed to loss or lineage skewing of keratinocytes stem cells and immune cells, and/or the regulation of their niches, altering normal homeostasis and tissue repair.

Naked mole-rats (NMRs) are small poikilothermic and hairless rodents native to East Africa, where they live underground in eusocial colonies. These mouse-sized rodents live almost five times longer than expected on the basis of body size, with a maximum lifespan exceeding 37 years in captivity and up to 17 years in their natural habitat. Despite being the longest-lived rodent, NMR do not show any increase in age-specific hazard of mortality in defiance of Gompertz's law and all of the classical signs of aging such as decreased fertility, muscle atrophy, bone loss, changes in body composition or metabolism seem to be mostly absent in these animals.

We used single-cell RNA-sequencing (scRNA-seq), to obtain the unbiased molecular RNA profile of the NMR epidermal cell populations. By profiling 10,000+ cells from skin epidermis in young and older NMR, we found that epidermal compartments and cell populations, especially the stem cells pool, remained unaffected despite aging. Igfbp3, expressed by keratinocyte stem cells and known to play a major role during epidermal homeostasis, was found upregulated in older animals, contrary to what is observed in other species. In addition, functional skin healing experiments revealed that NMR skin healing closure was similar in young and older animals.


so what does kill NMR?

Posted by: erasmus at May 19th, 2022 5:39 AM

@erasmus: The same thing as kills the young NMR (predation, disease, fighting amongst themselves). They even get some of the diseases we associate with old age, but the rate doesn't increase with age, violating the Goempertz Law. That's what makes them negligibly senescent. Here are a couple of interesting articles about them:

A good popular article about NMR:

A good journal article discussing the myths about the NMR. Look specifically at "Myth 27" at the bottom for a discussion of non-aging, which they state is not a myth:

Posted by: Neil at May 19th, 2022 1:41 PM

@Neil: Many thanks for this

Posted by: erasmus at May 19th, 2022 4:16 PM
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