The naked truth: a comprehensive clarification and classification of current ‘myths’ in naked mole‐rat biology

Abstract

The naked mole‐rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g. its tolerance of variable oxygen availability), which may be pertinent to several human disease states, including ischemia/reperfusion injury and neurodegeneration. A recent article entitled ‘Surprisingly long survival of premature conclusions about naked mole‐rat biology’ described 28 ‘myths’ which, those authors claimed, are a ‘perpetuation of beautiful, but falsified, hypotheses’ and impede our understanding of this enigmatic mammal. Here, we re‐examine each of these ‘myths’ based on evidence published in the scientific literature. Following Braude et al., we argue that these ‘myths’ fall into four main categories: (i) ‘myths’ that would be better described as oversimplifications, some of which persist solely in the popular press; (ii) ‘myths’ that are based on incomplete understanding, where more evidence is clearly needed; (iii) ‘myths’ where the accumulation of evidence over the years has led to a revision in interpretation, but where there is no significant disagreement among scientists currently working in the field; (iv) ‘myths’ where there is a genuine difference in opinion among active researchers, based on alternative interpretations of the available evidence. The term ‘myth’ is particularly inappropriate when applied to competing, evidence‐based hypotheses, which form part of the normal evolution of scientific knowledge. Here, we provide a comprehensive critical review of naked mole‐rat biology and attempt to clarify some of these misconceptions.

Aging clocks, entropy, and the limits of age-reversal

“…We speculate that the evolution of long-lived mammals may have provided an example of tuning the effective temperature. Naked mole rats are known for their exceptional stress resistance, DNA repair efficacy [44][45][46][47], and translational fidelity [48,49]. Both factors should reduce the noise in the regulatory circuits and lower the effective temperature of the system.…”

Epigenetic aging of the demographically non-aging naked mole-rat

“…The NMR lifespan is fivefold greater than that predicted allometrically based on its body size 2 . This extreme longevity of NMRs is accompanied by a nonincreasing mortality rate that led to the conclusion that the NMR is a non-aging mammal [6][7][8] . Although the lack of demographic aging is most confidently revealed up to the age of 12 years (because the vast majority of examined animals were within this age range) 6,9 , this age span is two times longer than the lifespan expected based on body size and 20-fold longer than the possible onset of reproduction 7 .…”

“…Although the lack of demographic aging is most confidently revealed up to the age of 12 years (because the vast majority of examined animals were within this age range) 6,9 , this age span is two times longer than the lifespan expected based on body size and 20-fold longer than the possible onset of reproduction 7 . The NMR was shown to resist age-related diseases such as cancer and cardiovascular disease [10][11][12] , shows no change in body composition and metabolic profiles with age 13 , and in general, its observed health deterioration (e.g., cataracts and osteoarthritis) do not appear to change in severity or frequency as age increases 8 . However, NMRs do exhibit age-related changes, such as decreased activity and altered (lighter and parchment-like) skin 1,2,5 .…”

MicroRNA Cues from Nature: A Roadmap to Decipher and Combat Challenges in Human Health and Disease?

“…Interestingly, the miRNA involvement in responses to hypoxia have been studied and many oxygen-responsive miRNAs (OxyMiRs) on major metabolic pathways were identified. Hypoxia is also one primary cause of tumor induction in some forms of the cancers [ 65 , 66 ]. An international collaborative study from our lab explored the hypoxia-induced miRNA responses in the brain of naked mole rats and showed that many differentially expressed miRNAs were involved in neuroprotection and anti-apoptotic responses [ 67 ].…”