Naked mole-rats are extremely long-lived rodents with a lifespan of up to 40 years, during which cellular and tissue aging is rarely observed. In this study, we analyzed the extracellular matrix (ECM) of naked mole-rat skin at the molecular level to elucidate the molecules involved in anti-aging and their localization. Raman spectroscopy and Fourier transform infrared spectroscopy were applied to investigate the hierarchical structure of the ECM, showing that, whereas the epidermis of aged mice had thinned, the epidermis of naked mole-rats became thickened and hyaluronic acid (HA) was distributed under the basement membrane. Furthermore, naked mole-rat skin had a regular skin texture and flexibility, allowing the maintenance of a youthful appearance. Hyaluronic acid in naked mole-rats characteristically exists as clusters (chain HA) in skin tissue, where it is thought to permit moisture retention and maintain elasticity, contributing to the skin's youthful appearance. These results suggested that not only the density of ECM but also its spatial distribution and topographic properties are important for skin anti-aging. Our findings may contribute to the elucidation of skin disease pathology, the development of therapeutic gel scaffolds, and the control of aging.
Evaporation is one of the most important pathways of water and heat loss for terrestrial vertebrates and can be partitioned into cutaneous (CEWL) and respiratory (REWL) components of total evaporative water loss (TEWL). Subterranean mammals inhabiting burrows with high humidity and relatively high ambient temperatures (Ta) face significant thermoregulatory challenges. We examined the effects different Tas (27.5, 32 and 37.5 °C) on the partitioning of TEWL in two social African mole-rats that differ in pelage. In the naked mole-rat (Heterocephalus glaber), TEWL increases ∼33 % with increasing Ta, resulting from the ∼63 % increase in CEWL and ∼69 % of heat is lost via evaporation. In Micklem's mole-rat (Fukomys micklemi), TEWL increases ∼57 %, but this is related to the ∼85 % increase in REWL and only ∼35 % of its heat is dissipated via evaporation. In both species, body temperature increased to 39 °C at 37.5 °C, indicating that heat dissipation was not fully effective. In the naked mole-rat, the increase of CEWL may play a decisive role in complex thermoregulation in hot environments, as cutaneous evaporative cooling does not entail additional metabolic costs. In contrast, Micklem's mole-rats rely more on non-evaporative mechanisms, as CEWL remains unchanged. Evaporative cooling may therefore be more energetically costly in this species, while fur is likely to enhance thermoregulation in colder environments. Finally, we compared evaporation within thermoneutrality (standard EWL) in both species with other fossorial and surface-living rodents to determine whether lifestyle has an effect on evaporation. We found that standard EWL was higher in fossorial rodents, suggesting that high burrow humidity does not constrain minimal evaporative capacity.
Skin serves as a barrier against the external environment and is a primary defense against pathogens. Cutaneous pH is part of that defense as pH affects enzyme production, activation, and efficiency within skin. Skin pH is influenced by multiple factors, although little research is available on wildlife. Most mammals have neutral to slightly acidic skin, while increased skin alkalinity is associated with a predisposition to cutaneous infections. The long life span, lack of fur, and eusocial nature of naked mole-rats (Heterocephalus glaber) make them an interesting study species for investigating patterns in skin pH. We measured skin pH over six months in captive naked mole-rats to determine variation among ages, sex, social status, the queen's reproductive status, body parts, and skin health issues. The overall mean skin pH was 8.0 ± 0.8 and ranged up to 10.0, the highest skin pH ever reported among mammals (n = 1807 measurements from 79 individuals, pH range 5.68-10.0). The skin pH of colony members decreased as the colony queen's pregnancy advanced, which may be due to elevated estradiol levels in colony members. The skin pH of the head region was more acidic than the body, which may be due to the presence of skin glands. Skin pH did not vary with social status, age, or sex. Given the alkaline skin observed in naked mole-rats and the fact that skin alkalinity is detrimental in other mammalian species, naked mole-rats present an intriguing study system for future investigations of skin function.
The naked mole-rat (Heterocephalus glaber) is a fascinating model organism which challenges conventional paradigms in evolutionary developmental biology. As one of the two known eusocial mammals with a reproductive hierarchy akin to social insects, the naked mole-rat presents an exceptional system for studying the interplay between social structure, environmental adaptation, and developmental plasticity. This chapter explores how the species' unique reproductive strategies-including lifelong fertility, postnatal oogenesis, and social suppression of reproduction-reshape our understanding of mammalian reproductive aging. The queen, the sole breeding female within a colony, maintains an exceptionally large ovarian reserve throughout life, defying the prevailing dogma of a fixed oocyte pool and progressive depletion. Unlike other mammals, germ cells in the naked mole-rat continue to proliferate postnatally, offering unprecedented insights into the regulation of ovarian function and reproductive longevity. Additionally, the integration of genomic, epigenetic, and neuroendocrine mechanisms underlying eusociality provides a rare perspective on how developmental processes can be shaped by cooperative behaviors and environmental constraints. By situating these traits within an evo-devo framework, this chapter underscores the naked mole-rat's potential to advance research in several fields such as aging, reproductive biology, and the evolution of complex social systems.
Eusociality, the highest level of social organization, is rare among vertebrates and is best exemplified by two African mole-rat species (Bathyergidae). The lifetime monogamy hypothesis suggests that monogamy enhances genetic relatedness within colonies, favoring the evolution of cooperative behaviors and eusociality. While strongly supported in eusocial insects, its role in vertebrates remains unclear. We evaluated this hypothesis in the Bathyergidae to determine the role of monogamy in the evolution of eusociality in vertebrates. We evaluated two predictions: (1) eusociality should be restricted to monogamous lineages, i.e., monogamy is a precondition of eusociality; and (2) factors additional to monogamy are required for eusociality to evolve. To test these predictions, we inferred a time-calibrated phylogeny for most species of Bathyergidae and combined it with mating system and sociality data to estimate ancestral states and assess evolutionary correlations. We inferred an ancestral monogamous state for social and eusocial African mole-rats. One of the evolutionary transitions with the highest rate of change was from monogamy + solitary to monogamy + social. Our results are consistent with monogamy representing a necessary prerequisite for the evolution of obligate eusociality, while also indicating that additional ecological and life-history factors are required for eusociality to evolve and intensify.
The naked mole-rat (Heterocephalus glaber) defies mammalian norms with lifelong fertility and postnatal oogenesis. Unlike most mammals, which experience reproductive senescence due to depletion of a finite ovarian follicle pool, naked mole-rat queens maintain fertility for their entire 30+-year lifespan through multiple mechanisms, including postnatal oogenesis, an exceptionally large ovarian reserve, and maintenance of primordial germ cells into adulthood. This review explores the unique reproductive biology of naked mole-rats within the context of their eusocial lifestyle, examining how social suppression of reproduction in subordinates, the role of very-high-molecular-weight hyaluronan (vHMW-HA) in cancer resistance and tissue maintenance, and the maintenance of germline stem cell populations contribute to their extraordinary reproductive longevity. We discuss the evolutionary advantages of eusociality, mechanisms of reproductive suppression and activation, and the potential of naked mole-rats as a research model for understanding ovarian aging and developing fertility-preserving therapies in humans.
The naked mole-rat (Heterocephalus glaber) is a long-lived mammal with resistance to cancer and hypoxia, suggesting the evolution of robust proteostasis networks. The ribosome, central for protein synthesis, is key to cellular stress responses and has an unusual feature: the 28S rRNA split; however, the details of its organization remain unknown. Here, we present high-resolution cryo-EM structures of the naked mole-rat 80S ribosome in four states of the elongation cycle. The structures reveal a conserved overall architecture and rRNA modification landscape compared to other mammals, and provide an atomic-level view of the distinct break in the 28S rRNA. This cleavage event, located in the D6 expansion segment, is structurally stabilized by a network of interactions with surrounding ribosomal proteins, maintaining the integrity of the large subunit. Our comparative analysis revealed that this compensatory network preserves a canonical architecture that is nearly indistinguishable from intact mouse and human ribosomes. These findings resolve the structural basis of this distinct cleavage, showing that it is a stable, integrated feature whose function is likely linked to more subtle regulatory mechanisms, rather than inducing major structural rearrangements.
Captivity represents a profound environmental shift that can induce physiological acclimation, yet its effects on metabolic rate remain poorly resolved, particularly in subterranean mammals. African mole-rats (Bathyergidae) are frequently studied under captive conditions, despite wide variation in acclimation periods prior to metabolic assessment. Here, we tested whether prolonged captivity alters resting metabolic rate (RMR) and related physiological traits in the highveld mole-rat Cryptomys hottentotus pretoriae, and whether such changes are associated with body mass and sex. Using open-flow respirometry, we measured RMR, mass-specific RMR (msRMR) and respiratory quotient (RQ) in the same population of wild-caught animals assessed 7 days post-capture (wild) and again after 12 months in captivity (captive). Whole-animal RMR did not differ between wild and captive groups, nor between sexes. However, msRMR was 26.1% lower following captivity, coincident with a 28.1% increase in mean body mass. This mass gain was strongly sex specific: males increased body mass by 52.4%, whereas females showed no significant change. Despite this, sex did not independently explain variation in RMR or msRMR. Captive animals also exhibited lower RQ values than recently captured individuals, suggesting shifts in substrate utilisation or energetic state. Together, these results indicate that apparent reductions in msRMR following captivity are driven primarily by increases in metabolically inactive tissue rather than suppression of whole-animal metabolic rate. Our findings highlight the importance of accounting for captivity-induced changes in body mass and composition when interpreting metabolic data, and caution against direct comparisons between unacclimated and long-term captive animals.
MicroRNAs play crucial roles in post-transcriptional regulation during environmental stress, yet their contribution to hypoxia adaptation in naturally hypoxia-tolerant species remains poorly understood. Here, we characterized the miRNA expression profile in kidneys of the naked mole-rat (Heterocephalus glaber), a subterranean rodent renowned for its exceptional hypoxia tolerance. Small RNA from naked-mole rat kidneys was sequenced under normoxic and hypoxic conditions to predict miRNA-mRNA interactions during low-oxygen stress. Bioinformatic analysis identified differentially expressed miRNAs and used pathway enrichment to predict regulatory mechanisms controlling kidney adaptation to hypoxia. Upregulated miRNAs, including let-7c-5p and miR-29a-3p target genes involved in cell cycle progression, extracellular matrix remodeling, and metabolic pathways, corresponding with negative enrichment of these processes. Conversely, downregulated miRNAs relieve inhibition of transcripts involved in chromatin remodeling, RNA processing, and immune signaling, aligning with positive enrichment of these adaptive pathways. Gene Ontology cellular component analysis suggested systematic subcellular reorganization, with suppression of extracellular and secretory compartments and enhancement of nuclear, RNA processing, and cytoskeletal structures. Notably, hypoxia induced upregulation of ribonucleoprotein complexes, spliceosomal machinery, and histone methyltransferase complexes, while downregulating extracellular matrix components and secretory pathway structures. This coordinated miRNA response appears to optimize energy utilization by suppressing non-essential pathways while selectively enhancing survival mechanisms through targeted post-transcriptional control; however further studies are required to confirm these findings. Our findings provide novel insights into the molecular mechanisms underlying the remarkable hypoxia tolerance of naked mole-rats and highlight miRNA-mediated regulation as a key adaptive strategy in mammalian hypoxic survival.
Ribosomes are central to protein synthesis in all organisms. In mammals, the ribosome functional core is highly conserved. Remarkably, two rodent species, the naked mole-rat (NMR) and tuco-tuco, display fragmented 28S ribosomal RNA (rRNA), coupled with high translational fidelity and long lifespan. The unusual ribosomal architecture in the NMR and tuco-tuco has been speculated to be linked to high translational fidelity. Here, we show, by single-particle cryo-electron microscopy, that despite the fragmentation of their rRNA, NMR and tuco-tuco ribosomes retain their core functional architecture. Compared to ribosomes of the guinea pig, a phylogenetically related rodent without 28S rRNA fragmentation, ribosomes of NMR and tuco-tuco exhibit poorly resolved density for certain expansion segments. In contrast, the structure of the guinea pig ribosome shows high similarity to the human ribosome. Enhanced translational fidelity in the NMR and tuco-tuco may stem from subtle, allosteric effects in dynamics, linked to rRNA fragmentation.
Based on von Békésy's premise that "The physical laws served as guidelines for the evolution of the structures and functions of the middle and inner ear," we aimed to understand how the unique subterranean acoustic environment, which promotes the propagation of low-frequency sounds and thereby selects for enhanced low-frequency hearing, influences functional adaptations reflected in the morphological convergence of the cochlea in subterranean African mole-rats (Bathyergidae). We conducted a morphometric analysis of the cochlea in 12 species representing all six genera of African mole-rats, spanning a body mass range of 30-2000 g. Cochlear partitions were examined using light microscopy following the standard surface specimen technique. The mole-rat cochleae has 3-4.3 coils. The length of the basilar membrane (BM) varies from 6.5 to 15.6 mm. Mean densities of inner hair cells (IHC) range from 104 to 122, whereas outer hair cells (OHC) range from 390 to 480 per 1 mm. Hair cell density increased slightly from the base towards the apex in all species studied. The radial width of the cuticular plates of the three rows (triad) of OHC, shown in previous studies to mirror BM width, increased continuously from, on average, 22 ± 3 µm at the base to 35 ± 6 μm at the apex. Length of BM, width of the OHC triad and total number of hair cells (and thus hearing resolution capabilities) are related to body size. When compared to other mammals, the cochleae of bathyergids exhibit quantitative characteristics that closely resemble the apical regions of the cochleae in other species-specifically, those segments tuned to low frequencies. Moreover, the width of OHC triads was strongly correlated with the tonotopic organization of frequencies along the organ of Corti, confirming its value as a structural predictor of auditory capability.
(1) Background: The naked mole-rat (Heterocephalus glaber) survives hypoxia-reoxygenation stresses by utilizing metabolic rate depression, achieved in part by downregulating nonessential genes and processes to conserve endogenous cellular resources and prevent buildup of toxic waste byproducts. Tight molecular control of protein degradation (specifically the ubiquitin-proteasome system) is a potent regulatory tool for maintaining muscle integrity during hypoxia, but how this system is regulated in the heart of hypoxia-tolerant species is poorly understood. (2) Methods: The protein expression levels of cullin-RING E3 ligases (specifically CRL4 architecture), deubiquitinating enzymes, and proteasomal activity were assayed in cardiac tissues from H. glaber exposed to 24 h of normoxia or hypoxia in vivo. (3) Results: Overall, the protein expression of E3 ligases decreased, whereas expression of deubiquitinating enzymes increased during hypoxia, all of which play roles in themes of oxidative stress, heightened DNA damage repair, and the HIF-1-VHL-NFκB axis. Proteasomal activity was elevated during hypoxia, which conceivably links to the oxidative stress theory of aging and longevity of H. glaber. (4) Conclusions: Taken together, our results expand current research into protein degradation and extreme environmental stress responses, with a specific focus on cardiac mechanisms related to oxidative stress resistance along the hypoxia-longevity axis.
Environmental hypoxia imposes severe constraints on aerobic metabolism, yet the naked mole-rat (Heterocephalus glaber) achieves remarkable resilience against low oxygen stress through profound metabolic suppression and substrate flexibility. To investigate the molecular basis of glucose regulation under low oxygen, we examined the insulin and insulin-like growth factor (IGF) signaling pathways across developmental stages and social castes. Juvenile, subordinate adult, and queen NMRs were exposed to 1 h of normoxia (21% O₂) or acute hypoxia (3% O₂), and tissues were analyzed for the expression of igf1, igf2, insr, and glucose/fructose transporters (glut1, glut4, glut5) at both gene and protein levels. Hypoxia markedly suppressed igf1, igf2, and insr expression in the brain of juveniles and subordinates (50–90% reduction), while promoting glut1 upregulation in heart and kidney, suggesting tissue-specific preservation of glucose uptake capacity in energetically critical organs. In contrast, queens exhibited a pronounced downregulation of glut4 and glut5 expression in muscle and liver, indicating reduced glucose and fructose utilization. These findings reveal that metabolic regulation under hypoxia is modulated not only by oxygen availability but also by social hierarchy and physiological role. Subordinates and juveniles maintain glucose transport to sustain activity during acute hypoxia, whereas queens employ a more energy-conserving phenotype aligned with their sedentary reproductive function. Collectively, this study provides the first evidence that IGF-mediated glucose signaling in NMRs operates in a caste- and tissue-specific manner, offering mechanistic insight into how social structure and metabolic flexibility jointly support survival under extreme hypoxic stress.
The naked mole-rat (NMR), Heterocephalus glaber, is an unusual mammal that lives underground in eusocial colonies. NMRs show remarkable longevity and are resistant to cancer, neurodegeneration, and cardiovascular disease. The gut microbiome is known to modulate human health and disease; here, we investigate the microbiome of NMRs, comparing fecal samples from individuals over different social ranks and over a span of more than three decades. In contrast to a cohort of C57BL6/J mice, which showed extensive age-related changes, we found little difference in the microbiota of NMRs from different age cohorts. Only the archaea Methanomassiliicoccus intestinalis, which was present in the NMR gut but not the murine gut, showed an increased proportion with older age. Pregnant queens were found to have higher microbial diversity, potentially a consequence of their aggressive coprophagia. Overall, these findings provide a rich and dynamic picture of the NMR microbiome and starting points for future investigation.
The naked mole-rat (NMR) is a subterranean rodent known for its unique thermal biology, exceptional longevity, and resistance to cancer and hypoxia. However, its thermal biology remains controversial, with various reports describing NMRs as poikilotherms, heterotherms, mesotherms, or partial homeotherms. Here, we investigated whether the thermogenic potential of NMR brown adipose tissue and its UCP1 differ from those in mice and whether the lack of thermal insulation causes extreme changes in NMR body temperature upon cold exposure. Through longitudinal molecular, thermal, metabolic, and behavioral measurements, we found that NMRs initiated nonshivering thermogenesis and elevated body temperature but could not sustain it due to excessive heat loss. Our results suggest that NMRs represent a unique thermoregulatory category that does not fit neatly into traditional classifications. In vitro and in vivo experiments showed that the NMR UCP1 is functional and can be activated and inhibited as expected for most other mammals. We further demonstrated that artificial insulation can partially restore thermoregulatory capabilities in NMRs. This study employs an advanced methodology to characterize the thermal biology of NMRs and helps resolve a long-standing controversy in the field.
The naked mole-rat (NMR; Heterocephalus glaber) is a subterranean rodent native to the arid regions of the Horn of Africa. The NMR is the longest-lived rodent and is known for its distinctive physiological and social traits. This species has become a notable model organism for studying aging, cancer biology, behavioral ecology, and reproduction. Recently, NMRs have gained attention because their gastrointestinal tract features an exceptionally strong intestinal barrier, a large number of goblet cells, a thicker mucin layer, and reduced gut permeability. The NMR gut microbiome, similar to that observed in human centenarians, is highly diverse and characterized by a high microbial load. In fact, Hart et al (2026) demonstrated that spontaneous infection with Citrobacter braakii in the NMR causes clinical symptoms and histopathological changes that are very similar to those observed in human colitis. If left untreated, the disease can progress and become fatal. However, probiotic treatment can reverse the clinical and histopathological phenotypes. These findings indicate that, in addition to serving as a powerful model for aging, cancer, and reproduction, the NMR may also serve as a powerful tool for studying human diseases such as gut dysbiosis, gut barrier dysfunction, and colitis. © 2026 The Pathological Society of Great Britain and Ireland.
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The naked mole-rat Heterocephalus, a hairless, subterranean rodent from the Horn of Africa, has attracted scientific interest due to its cooperative breeding, poikilothermy, longevity, resistance to cancer, and tolerance to pain and hypoxia, among others. Genomic analyses of H. glaber, traditionally considered a single species, reveal three highly divergent lineages. One of these, identified as H. phillipsi Thomas 1885, shows deep genetic divergence (~4.1 Ma) and distinct morphology, notably reduced third molars, warranting recognition as a distinct species. The remaining two lineages, previously designated as the subspecies H. g. glaber Rüppell 1842 and H. g. ansorgei Thomas 1903, diverged around 2.3 Ma and their morphological differentiation is less pronounced. Each of the lineages occupies distinct environmental conditions, with H. phillipsi inhabiting extremely harsh habitats. The finding of an unexpected diversity within this key biomedical model opens new avenues across various fields of research.
Bite force is a simple trait indicating an animal's performance related to foraging, social dominance, and defence, all of which influence individual reproductive success. We examine the effect of breeding status on bite force in four social species of Fukomys, a genus of subterranean African rodents (Bathyergidae). These species are cooperative breeders, where reproduction is limited typically to a breeding pair. We collected in vivo bite force data, head width, and upper incisors width from 404 individuals from 75 families and tested whether breeders exhibit stronger bite force. We reveal that breeding males of all four species outperform non-breeders, with bite force in non-breeding males and females being 12% and 22% lower, respectively. In contrast, breeding females underperform relative to other categories, with bite force approximately 31% lower than in breeding males, and many are reluctant to bite. Head width and upper incisors width corroborate these findings. We propose that breeding males require a stronger bite force because of repeated competition with non-related males that may try to enter the family. In contrast, there is much less competition for the breeding position among females, as females rarely intrude into established families.
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