A Hypothesis to Explain Cancers in Confined Colonies of Naked Mole Rats

Abstract

Naked mole rats (NMRs) are subterranean eusocial mammals, known for their virtual absence of aging in their first 20 to 30 years of life, and their apparent resistance to cancer development. As such, this species has become an important biological model for investigating the physiological and molecular mechanisms behind cancer resistance. Two recent studies have discovered middle and late-aged worker (that is, non-breeding) NMRs in captive populations exhibiting neoplasms, consistent with cancer development, challenging the claim that NMRs are cancer resistant. These cases are possibly artefacts of inbreeding or certain rearing conditions in captivity, but they are also consistent with evolutionary theory.We present field data showing that worker NMRs live on average for 1 to 2 years. This, together with considerable knowledge about the biology of this species, provides the basis for an evolutionary explanation for why debilitating cancers in NMRs should be rare in captive populations and absent in the wild. Whereas workers are important for maintaining tunnels, colony defence, brood care, and foraging, they are highly vulnerable to predation. However, surviving workers either replace dead breeders, or assume other less active functions whilst preparing for possible dispersal. These countervailing forces (selection resulting in aging due to early-life investments in worker function, and selection for breeder longevity) along with the fact that all breeders derive from the worker morph, can explain the low levels of cancer observed by these recent studies in captive colonies. Because workers in the field typically never reach ages where cancer becomes a risk to performance or mortality, those rare observations of neoplastic growth should be confined to the artificial environments where workers survive to ages rarely if ever occurring in the wild. Thus, we predict that the worker phenotype fortuitously benefits from antiaging and cancer protection in captive populations.

Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age

“… ( A ) Repeated calculation of Kaplan-Meier survival, using the original data from Figure 1 (green) and iteratively adding month-resolution data (navy), less-than-month-resolution data (yellow), and inequality-derived data (cyan; see Materials and methods for further descriptions). Expected survivals from T sex (purple) using either our consistent estimate for mortality hazard (8 * 10 −5 per day) or an estimate from Hochberg ( Hochberg et al, 2016 ) for H. glaber survival in the wild (0.6 per year). ( B ) Hazard estimates across each of the lifespan bins from Figure 1B , calculated for each of the expanded data sets, as described and colored in panel ( A ).…”

“…Twelve years can also be considered in the context of the expected total lifespan of a naked mole-rat based on its body size ( de Magalhães et al, 2007b ): this 35-gram rodent would be expected to live up to six years, but instead has not shown the first sign of demographic aging at twice that age. Twelve years could finally be considered from the perspective of natural lifespan in the wild, which is estimated to be 2–3 years for the naked mole-rat ( Hochberg et al, 2016 ).…”

“…This maximum lifespan is five-fold greater than predicted allometrically for a 40 g rodent ( Edrey et al, 2011 ). Even in the wild, naked mole-rats are also considered to be very long-lived rodents with reports of breeding females remaining 17 years in the same colony while non-breeders remain 2–3 years ( Hochberg et al, 2016 ). In sharp contrast, other rodents generally last only a season in the wild, with their young-age deaths attributed to predation, inclement weather, parasites, pathogens and lack of food resources ( Morgen, 2003 ; David and Jarvis, 1985 ; Boonstra and Krebs, 2012 ; Krebs et al, 1995 ; Krebs et al, 1973 ).…”

A framework for how environment contributes to cancer risk

“…), and that occasional cancer may have both an evolutionary and ecological basis (Hochberg et al . ). Work on captive African and Asian elephants reveals that they have 20 copies of the TP53 tumour suppressor gene, suggesting that the total stem cell population in an elephant can tolerate numerous mutations with little risk of any single stem cell lineage transforming into a neoplasm (Abegglen et al .…”

The Naked Mole Rat: A Unique Example of Positive Oxidative Stress

“…Naked mole rats ( Heterocephalus glaber ), first described by Rüppell in 1842, are the longest living rodents known. About the size of a mouse, this hairless poikilothermic eusocial rodent lives almost ten times as long as a mouse, with a maximum lifespan of about 32 years in captivity and 17 years in the wild [30, 31]. The naked mole rat is an outlier on the allometric relationship between body mass and maximum lifespan [32–34].…”