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.

The development of a precise blood or skin tissue DNA Epigenetic Aging Clock for Odontocete (OEAC) would solve current age estimation inaccuracies for wild odontocetes. Therefore, we determined genome-wide DNA methylation profiles using a custom array (HorvathMammalMethyl40) across skin and blood samples (n = 446) from known age animals representing nine odontocete species within 4 phylogenetic families to identify age associated CG dinucleotides (CpGs). The top CpGs were used to create a cross-validated OEAC clock which was highly correlated for individuals (r = 0.94) and for unique species (median r = 0.93). Finally, we applied the OEAC for estimating the age and sex of 22 wild Norwegian killer whales. DNA methylation patterns of age associated CpGs are highly conserved across odontocetes. These similarities allowed us to develop an odontocete epigenetic aging clock (OEAC) which can be used for species conservation efforts by provide a mechanism for estimating the age of free ranging odontocetes from either blood or skin samples.

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.

Concentrations of plasma adrenocorticotropic hormone (ACTH), cortisol, and aldosterone were investigated in three adult beluga whales (Delphinapterus leucas), held in a large outdoor public aquarium exhibit. The purpose of this study was to evaluate resting concentrations of these hormones and associated diurnal variations with routine interactions and medical procedures. Resting blood samples were collected voluntarily from the ventral fluke veins at predetermined times of the day to evaluate diurnal changes in analyte concentrations. In addition, hematology and serum chemistry analyses were performed to monitor health status and evaluate changes related to physical exam procedures. Analogous sampling was conducted during out‐of‐water physical examinations and before and after wading‐contact sessions (WCS). Baseline stress hormone concentrations (± SD) were as follows: plasma ACTH (8.41 ± 5.8 pg/mL), serum cortisol (1.80 ± 0.71 g/dL), and serum aldosterone (11.42 ± 5.5 pg/mL). Plasma ACTH and cortisol concentrations were consistently higher in early morning than evening, while aldosterone was higher in the evening. All stress‐related hormones were significantly elevated during physical examination. Plasma ACTH concentrations were most increased, 5–10‐fold, during physical examination, whereas cortisol and aldosterone showed 2–4‐fold elevations. Stress response analytes measured during the WCS did not differ significantly from baseline concentrations.