Aging is often perceived as a degenerative process caused by random accrual of cellular damage over time. In spite of 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, it is difficult to ignore the likelihood that a defined and shared mechanism instead, underlies the aging process. To address this, we generated 10,000 methylation arrays, each profiling up to 37,000 cytosines in highly-conserved stretches of DNA, from over 59 tissue-types derived from 128 mammalian species. From these, we identified and characterized specific cytosines, whose methylation levels change with age across mammalian species. Genes associated with these cytosines are greatly enriched in mammalian developmental processes and implicated in age-associated diseases. From the methylation profiles of these age-related cytosines, we successfully constructed three highly accurate universal mammalian clocks for eutherians, and one universal clock for marsupials. The universal clocks for eutherians are similarly accurate for estimating ages (r>0.96) of any mammalian species and tissue with a single mathematical formula. Collectively, these new observations 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 and compelling evidence.

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.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

No abstract

Context The ringed seal (Phoca hispida), a small phocid seal with a circumpolar Arctic distribution and a strong association with sea ice, occurs at the southern limit of its range in Hudson and James Bays: an area that experiences complete ice cover in winter and complete open water in summer. Because of the high seasonal variability in environmental conditions, it is expected that ringed seals experience seasonal changes in diet and foraging habitat, which will be reflected in body condition and biomarkers of stable isotopes and fatty acids. Aims The purpose of the present study was to investigate intra-annual variation in the feeding habits and body condition of the ringed seal. Methods Tissue samples and morphological measurements from south-eastern Hudson Bay ringed seals were obtained every month during the Inuit subsistence hunt from November 2009 to May 2011 (n = 192). Muscle samples were used for δ15N and δ13C stable isotope analysis, blubber was used for analysis of fatty acid composition, bodyweight and sculp weight were used to estimate percentage blubber, and lower right canines were used to determine age. Key results Fatty acid composition, δ15N, and δ13C varied significantly by season, suggesting seasonal changes in foraging habitat and diet. Variation in percentage blubber indicated that poorest body condition occurs following the molting and fasting period, followed by a gradual increase from late summer through fall, with the highest body condition occurring in time for freeze-up in December. Key conclusions Patterns of δ13C indicate pelagic feeding during the open-water season (August–December) when fat and energy stores are replenished, increased benthic foraging during the period of ice cover (January–May), followed by a period of fasting during the spring molt (June–July). Fatty acid composition suggested seasonal changes in diet that could include increased importance of pelagic fish in the fall during the period of positive energy balance. Implications The first continuous collection of ringed seal tissue samples provided a comprehensive seasonal pattern of biomarker composition, which is baseline data that have important applications for short-term management and ecology studies as well as long-term conservation and monitoring programs.