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.

Keywords: ageing; cancer; ecology; eusociality; hypoxia; longevity; naked mole-rat; nociception; thermoregulation.

Fig 1

Sparsely distributed sensory vibrissae, although distributed all over the body, are very different to the fine, dense hair that constitutes the fur of most mammals. Photograph credit: Megan Smith.

Fig 2

Thermoregulatory terms explained. Here, antonyms are shown opposite to each other. ‘Homeotherm’ refers to the maintenance of a core body temperature (T _b) within a limited range (<2°C), whereas ‘poikilotherm’ refers to the thermal state whereby animals show large variability in T _b such that T _b is primarily dependent upon ambient temperature (T _a). ‘Ectothermy’ and ‘endothermy’ refer to the two main mechanisms involved in heat acquisition. ‘Ectothermy’ relies mainly on behaviourally controlled heat exchange with the environment, whereas ‘endothermy’ refers to endogenous heat production. Using this cartoon, one can deduce that a crocodile, given its large thermal inertia, is able to maintain homeothermy using ectothermic mechanisms, i.e. shuttling from cooler to warmer areas to maintain body temperature, whereas a monkey primarily uses facultative thermogenesis to maintain a constant body temperature. By contrast, despite employing endothermy, given their large surface area to volume ratio and high rates of heat loss the naked mole‐rat cannot regulate T _b effectively outside of a very narrow range of environmental T _a. MR, metabolic rate. Image modified from (Hislop & Buffenstein, 1994). Drawn with biorender.com

Fig 3

The behavioural audiogram of the naked mole‐rat in comparison with those of four other rodent species (see text for references). Rats and gerbils are murids; the other species are ctenohystricans.

Fig 4

(A) Liver gene‐expression profiles of growth hormone (GH)‐deficient (Ghrh ^−/−) mice and naked mole‐rats. Gene fold‐changes (FCs) were calculated relative to wild‐type mice for each organism, using ortholog conversion for naked mole‐rat genes (reciprocal best BLAST hits). Spearman's rank correlation coefficient for all genes on the plot and the correlation P‐value are shown in red. Of the genes that change substantially in both organisms (>twofold), those that change concordantly (blue) outnumber those that change non‐concordantly (black). Genes of special interest are labelled – insulin‐like growth factor 1 (IGF1; induced by GH) is down‐regulated in both organisms and sulfotransferase family 2A (Sult2a2) (repressed by GH) is upregulated in both organisms. Data for Ghrh ^−/− mice was obtained from GSE51108. Data for naked mole‐rats were generated by N. Rubinstein and R.B. and analysed by K.P. (B) Standard curves for commercial IGF1 enzyme‐linked immunosorbent assay (ELISA) (ALPCO 22‐IG1MS‐E01) generated using recombinant mouse and naked mole‐rat IGF1 proteins and four‐parameter logistic regression (4PL). (C) Concentration of IGF1 in blood plasma of young adult animals, measured using standard curves in B. Mice were 3.5 months old and naked mole‐rats were 2–2.3 years old; three females and two males were used in both groups. LOD, limit of detection.