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.

Around the world and across taxa, subterranean mammals show remarkable convergent evolution in morphology (e.g., reduced external ears, small eyes, shortened limbs and tails). This is true of sensory systems as well (e.g., loss of object vision and high frequency hearing). The naked mole-rat (Heterocephalus glaber) displays these typical subterranean features, but also has unusual characteristics even among subterranean mammals. Naked mole-rats are cold-blooded, completely furless, very longlived (> 30 years), and eusocial (like termites). They also live in large colonies, which is very unusual for subterraneans. Their cortical organization has reduced area for visual processing, utilizing 30% more cortex for tactile processing. They are extremely tolerant to oxygen deprivation, and can recover from 18 min of anoxia. Their pain pathway is reduced and they feel no pain from acidosis. They are the only rodent tested to date whose pheromone-detecting vomeronasal organ shows no postnatal growth. These features may be a result of this species' "extreme subterranean lifestyle" that combines living underground and living in large colonies. Many respiring animals cramped together in unventilated burrows elevates CO 2 levels, high enough to cause acidosis pain, and depletes O 2 concentrations low enough to kill other mammals. The naked mole-rat may be an extreme model of adaptation to subterranean life and provides insights into the complex interplay of evolutionary adaptations to the constraints of subterranean living. Anat Rec, 303:77-88, 2020.

Naked mole-rats (NMRs) are a long-lived animal that do not develop age-related diseases including neurodegeneration and cancer. Additionally, NMRs have a profound ability to consume reactive oxygen species (ROS) and survive long periods of oxygen deprivation. Here, we evaluated the unique proteome across selected brain regions of NMRs at different ages. Compared to mice, we observed numerous differentially expressed proteins related to altered mitochondrial function in all brain regions, suggesting that the mitochondria in NMRs may have adapted to compensate for energy demands associated with living in a harsh, underground environment. Keeping in mind that ROS can induce polyunsaturated fatty acid peroxidation under periods of neuronal stress, we investigated docosahexaenoic acid (DHA) and arachidonic acid (AA) peroxidation under oxygen-deprived conditions and observed that NMRs undergo DHA and AA peroxidation to a far less extent compared to mice. Further, our proteomic analysis also suggested enhanced peroxisome proliferator-activated receptor (PPAR)-retinoid X receptor (RXR) activation in NMRs via the PPARα-RXR and PPARγ-RXR complexes. Correspondingly, we present several lines of evidence supporting PPAR activation, including increased eicosapetenoic and omega-3 docosapentaenoic acid, as well as an upregulation of fatty acid-binding protein 3 and 4, known transporters of omega-3 fatty acids and PPAR activators. These results suggest enhanced PPARα and PPARγ signaling as a potential, innate neuroprotective mechanism in NMRs.

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