Biology subjects

Faulkes, C. G.

Publications and source records attributed to Faulkes, C. G..

8 recordsLinked to original sources

bioRxiv2026

Sociality, diurnal temperature range and isothermality: Significant determinants of mass-independent resting metabolic rate in subterranean African mole-rats (Superfamily Bathyergidae)

Animals exhibit a diverse range of sociality from the strictly solitary to the highly social. Different forms of sociality have evolved in response to ecological constraints and selective habitat pressures, which are governed by the energetic and fitness costs to an individual. Uniquely among mammals, the clade of African mole-rats (Bathyergidae and Heterocephalidae) covers three distinct life-history forms of sociality: solitary, social and eusocial species. This variety in social structure makes them a model clade to study how metabolic traits vary between different forms of sociality. Resting metabolic rates (RMR) of seven African mole-rat species, ranging from solitary to eusocial, were measured using open-flow respirometry. Results were combined with published data, enabling the inclusion and statistical analysis of 16 species in total. We identified distinct allometric scaling of RMR, with eusocial species exhibiting a considerably greater rise in RMR with increases in body mass. This is likely attributable to reproductive and behavioural divisions of labour, and mass-dependent colony roles in eusocial species. Phylogenetically-informed analyses further identified that sociality, in addition to select bioclimatic traits - diurnal temperature range ({degrees}C) and isothermality (%) - significantly explain variation in the mass-independent RMR of African mole-rats. These findings elucidate, for the first time, that sociality can be a determinant of RMR, and calls for further study to identify the wider significance of sociality on mammalian metabolism, as well as exploring the allometric scaling of metabolic rate with respect to mammalian sociality.

physiology↗

bioRxiv2023

Naked mole rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles

The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, RNAseq and metabolomics of cardiac tissue from naked mole-rats was compared to other African mole-rat genera. We identified metabolic and genetic adaptations unique to naked mole-rats including elevated glycogen, thus enabling glycolytic ATP generation during cardiac ischemia. Elevated normoxic expression of HIF-1 was observed while downstream hypoxia responsive-genes were down regulated, suggesting adaptation to low oxygen environments. Naked mole-rat hearts showed reduced succinate build-up during ischemia and negligible tissue damage following ischemia-reperfusion injury. These adaptive evolutionary traits reflect a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span. One Sentence SummaryNaked mole-rats have metabolic adaptations distinct from other subterranean genera rendering them resistant to cardiovascular pathology.

physiology↗

bioRxiv2021

Epigenetic predictors of maximum lifespan and other life history traits in mammals

Maximum lifespan of a species is the oldest that individuals can survive, reflecting the genetic limit of longevity in an ideal environment. Here we report methylation-based models that accurately predict maximum lifespan (r=0.89), gestational time (r=0.96), and age at sexual maturity (r=0.87), using cytosine methylation patterns collected from over 12,000 samples derived from 192 mammalian species. Our epigenetic maximum lifespan predictor corroborated the extended lifespan in growth hormone receptor knockout mice and rapamycin treated mice. Across dog breeds, epigenetic maximum lifespan correlates positively with breed lifespan but negatively with breed size. Lifespan-related cytosines are located in transcriptional regulatory regions, such as bivalent chromatin promoters and polycomb-repressed regions, which were hypomethylated in long-lived species. The epigenetic estimators of maximum lifespan and other life history traits will be useful for characterizing understudied species and for identifying interventions that extend lifespan.

evolutionary biology↗

bioRxiv2021

DNA methylation clocks show slower progression of aging in naked mole-rat queens

Naked mole-rats (NMRs) live an exceptionally long life, appear not to exhibit age-related decline in physiological capacity, and are seemingly resistant to age-related diseases. However, it has been unknown whether NMRs also evade aging according to a primary hallmark of aging: epigenetic changes. To address this question, we generated DNA methylation profiles from 329 tissues from animals of known age, at loci that are highly conserved between mammalian species, using a custom Infinium array (HorvathMammalMethylChip40). We observed strong aging effects on NMR DNA methylation, from which we developed seven highly accurate age estimators (epigenetic clocks) for several tissues (pan-tissue, blood, kidney clock, liver clock, skin clock) and two dual species (human-NMR) clocks. By identifying age-related cytosine methylation that are shared between NMR and humans, but not with the mouse, we identified genes and cellular pathways that impinge on developmental and metabolic processes that are potentially involved in NMR and human longevity. The NMR epigenetic clocks revealed that breeding NMR queens age more slowly than non-breeders, a feature that is also observed in some eusocial insects. CpGs associated with queen status were located near developmental genes and those that are regulated by the LHX3 transcription factor that controls pituitary development. In summary, our study demonstrates that despite a phenotype of reduced senescence, the NMR ages epigenetically through developmental and metabolic processes, and that NMR queens age more slowly than non-breeders.

developmental biology↗

bioRxiv2021

DNA Methylation Networks Underlying Mammalian Traits

Epigenetics has hitherto been studied and understood largely at the level of individual organisms. Here, we report a multi-faceted investigation of DNA methylation across 11,117 samples from 176 different species. We performed an unbiased clustering of individual cytosines into 55 modules and identified 31 modules related to primary traits including age, species lifespan, sex, adult species weight, tissue type and phylogenetic order. Analysis of the correlation between DNA methylation and species allowed us to construct phyloepigenetic trees for different tissues that parallel the phylogenetic tree. In addition, while some stable cytosines reflect phylogenetic signatures, others relate to age and lifespan, and in many cases responding to anti-aging interventions in mice such as caloric restriction and ablation of growth hormone receptors. Insights uncovered by this investigation have important implications for our understanding of the role of epigenetics in mammalian evolution, aging and lifespan.

evolutionary biology↗

bioRxiv2021

Universal DNA methylation age across mammalian tissues

Aging is often perceived as a degenerative process resulting from random accrual of cellular damage over time. Despite this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several different species, we hypothesized that one can build pan-mammalian clocks that measure age in all mammalian species. To address this, we generated data using 11,754 methylation arrays, each profiling up to 36 thousand cytosines in highly-conserved stretches of DNA, from 59 tissue-types derived from 185 mammalian species. From these methylation profiles, we constructed three age predictors, each with a single mathematical formula, termed universal pan-mammalian clocks that are accurate in estimating the age (r>0.96) of any mammalian tissue. Deviations between epigenetic age and chronological age relate to mortality risk in humans, mutations that affect the somatotropic axis in mice, and caloric restriction. We characterized specific cytosines, whose methylation levels change with age across most mammalian species. These cytosines are greatly enriched in polycomb repressive complex 2-binding sites, are located in regions that gradually lose chromatin accessibility with age and are proximal to genes that play a role in mammalian development, cancer, human obesity, and human longevity. Collectively, these results support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new compelling evidence. SUMMARYThis study identifies and characterizes evolutionarily conserved cytosines implicated in the aging process across mammals and establishes pan mammalian epigenetic clocks.

developmental biology↗

bioRxiv2020

Epidermal stem cell compartment remains unaffected through aging in naked mole-rats.

Skin represents an informative and convenient organ for the analysis of the aging process. Naked mole-rats (NMR) are subterranean rodents remarkable for their longevity, with unexplained resistance to skin aging. In middle-aged NMR, extensive in situ analysis indicated that skin compartments and cell types remained similar to young animals. Using single-cell RNA-sequencing, we found three classical cellular states defining a unique keratinocyte differentiation trajectory that did not appear to be altered during aging after pseudotemporal reconstruction. Finally, NMR skin healing closure was strictly comparable between the two age groups. These results indicate that the content in stem cell populations as well as the differentiation process are preserved during aging in NMR and that such properties are related to the healing process.

cell biology↗

bioRxiv2017

Molecular insights into the pathways underlying naked mole-rat eusociality

BackgroundEusociality is the highest level of social organization and naked mole-rats (NMR)s are amongst the few mammals showing this unique social behavior; nevertheless, little is known about the molecular mechanisms underlying the eusociality of NMRs.\n\nResultsGene expression profiling of NMR brain and gonads (ovary and testis), from animals belonging to different reproductive castes, revealed robust gene expression differences between reproductive and non-reproductive members of NMR colonies. In the brain, dopaminergic pathways appear to be potential players in NMR eusocial behaviour. Breeding animals (queens and breeding males) showed increased expression of genes involved in dopamine metabolism. Using immunohistochemistry, we notably found these differences to be in dopaminergic hypothalamic areas, which provide inhibitory control over the secretion of prolactin, amongst other regions. Furthermore, plasma prolactin concentrations were elevated in many non-breeders (of both sexes), often reaching levels exceeding that of pregnant or lactating queens, suggesting a role for hyperprolactinaemia in socially-induced reproductive suppression. We also found that the ovaries of non-breeding females are arrested at pre-pubertal stage. They contained fewer supporting stromal cells compared to queens, and had very low expression of the aromatase gene Cyp19A1 (a key enzyme in estrogen synthesis) compared to non-breeding females. In the testes, genes involved in post meiosis spermatogenesis and sperm maturation (Prm1, Prm2, Odf3 and Akap4) were highly expressed in breeding males compared to non-breeders, explaining the low sperm number and impaired sperm motility characteristic of non-breeding males.\n\nConclusionsOur study suggests that extreme reproductive skew, one of the defining features of eusociality, is associated with changes in expression of key components of dopamine pathways, which could lead to hypogonadism and a lifetime of socially-induced sterility for most NMRs.

neuroscience↗