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.

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.

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Background The gut microbiome is important to immune health, metabolism, and hormone regulation. Understanding host–microbiome relationships in captive animals may lead to mediating long term health issues common in captive animals. For instance, zoo managed African elephants (Loxodonta africana) and Asian elephants (Elephas maximus) experience low reproductive rates, high body condition, and gastrointestinal (GI) issues. We leveraged an extensive collection of fecal samples and health records from the Elephant Welfare Study conducted across North American zoos in 2012 to examine the link between gut microbiota and clinical health issues, reproductive hormones, and metabolic hormones in captive elephants. We quantified gut microbiomes of 69 African and 48 Asian elephants from across 50 zoos using Illumina sequencing of the 16S rRNA bacterial gene. Results Elephant species differed in microbiome structure, with African elephants having lower bacterial richness and dissimilar bacterial composition from Asian elephants. In both species, bacterial composition was strongly influenced by zoo facility. Bacterial richness was lower in African elephants with recent GI issues, and richness was positively correlated with metabolic hormone total triiodothyronine (total T3) in Asian elephants. We found species-specific associations between gut microbiome composition and hormones: Asian elephant gut microbiome composition was linked to total T3 and free thyroxine (free T4), while fecal glucocorticoid metabolites (FGM) were linked to African elephant gut microbiome composition. We identified many relationships between bacterial relative abundances and hormone concentrations, including Prevotella spp., Treponema spp., and Akkermansia spp. Conclusions We present a comprehensive assessment of relationships between the gut microbiome, host species, environment, clinical health issues, and the endocrine system in captive elephants. Our results highlight the combined significance of host species-specific regulation and environmental effects on the gut microbiome between two elephant species and across 50 zoo facilities. We provide evidence of clinical health issues, reproductive hormones, and metabolic hormones associated with the gut microbiome structure of captive elephants. Our findings establish the groundwork for future studies to investigate bacterial function or develop tools (e.g., prebiotics, probiotics, dietary manipulations) suitable for conservation and zoo management.

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.

Tropical Sedimentary Ancient DNA Preservation references in public databases. Of the remaining 7.7%, most of the data (93.0%) derive from Bacteria and Archaea, whereas only 0-5.8% are from Metazoa and 0-6.9% from Viridiplantae, in part due to unbalanced taxa representation in the reference data. The plant DNA record at ordinal level agrees well with local pollen data but resolves less diversity. Our animal DNA record reveals the presence of 41 native taxa (16 orders) including Afrotheria, Carnivora, and Ruminantia at Bwindi during the past 2200 years. Overall, we observe no decline in taxonomic richness with increasing age suggesting that several-thousand-year-old information on past biodiversity can be retrieved from tropical sediments. However, comprehensive genomic surveys of tropical biota need prioritization for sedimentary DNA to be a viable methodology for future tropical biodiversity studies.

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Using DNA methylation profiles ( n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.