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.
Summary The narwhal ( Monodon monoceros ) is a highly specialized endemic Arctic cetacean, restricted to the Arctic seas bordering the North Atlantic. Low levels of genetic diversity have been observed across several narwhal populations using mitochondrial DNA and microsatellites. Despite this, the global abundance of narwhals was recently estimated at ∼170,000 individuals. However, the species is still considered vulnerable to changing climates due to its high specialization and restricted Arctic distribution. We assembled and annotated a genome from a narwhal from West Greenland. We find relatively low diversity at the genomic scale and show that this did not arise by recent inbreeding, but rather has been stable over an extended evolutionary timescale. We also find that the current large global abundance most likely reflects a recent rapid expansion from a much smaller founding population.
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.
One of the last pristine marine soundscapes, the Arctic, is exposed to increasing anthropogenic activities due to climate-induced decrease in sea ice coverage. In this study, we combined movement and behavioral data from animal-borne tags in a controlled sound exposure study to describe the reactions of narwhals, Monodon monoceros, to airgun pulses and ship noise. Sixteen narwhals were live captured and instrumented with satellite tags and Acousonde acoustic-behavioral recorders, and 11 of them were exposed to airgun pulses and vessel sounds. The sound exposure levels (SELs) of pulses from a small airgun (3.4 L) used in 2017 and a larger one (17.0 L) used in 2018 were measured using drifting recorders. The experiment was divided into trials with airgun and ship-noise exposure, intertrials with only ship-noise, and pre- and postexposure periods. Both trials and intertrials lasted ∼4 h on average per individual. Depending on the location of the whales, the number of separate exposures ranged between one and eight trials or intertrials. Received pulse SELs dropped below 130 dB re 1 μPa2 s by 2.5 km for the small airgun and 4–9 km for the larger airgun, and background noise levels were reached at distances of ∼3 and 8–10.5 km, respectively, for the small and big airguns. Avoidance reactions of the whales could be detected at distances >5 km in 2017 and >11 km in 2018 when in line of sight of the seismic vessel. Meanwhile, a ∼30% increase in horizontal travel speed could be detected up to 2 h before the seismic vessel was in line of sight. Applying line of sight as the criterion for exposure thus excludes some potential pre-response effects, and our estimates of effects must therefore be considered conservative. The whales reacted by changing their swimming speed and direction at distances between 5 and 24 km depending on topographical surroundings where the exposure occurred. The propensity of the whales to move towards the shore increased with increasing exposure (i.e., shorter distance to vessels) and was highest with the large airgun used in 2018, where the whales moved towards the shore at distances of 10–15 km. No long-term effects of the response study could be detected.
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