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.

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.

The queen's chirp rules: Naked mole-rats are known for their eusocial lifestyle, living in colonies that consist of many workers and a single breeding queen. Little is known about how individuals within these colonies navigate the many interactions that must occur in such a complex cooperative group. Barker et al. show that calls emitted by individuals, in particular the common “chirp” call, convey information specific to the animal's group (see the Perspective by Buffenstein). Group differences are cultural, rather than genetic, and are related to the queen: Cross-fostered pups adopt their rearing colony's dialects, and dialects change with queen replacement. Science , this issue p. 503 ; see also p. 461

How the mole-rat lost its pain: Pain alerts our bodies that something is amiss and typically we stop the pain-causing activity. Numerous species of plants and prey animals take advantage of this response by producing pain-causing substances that are released during predation attempts. In turn, species that encounter these substances often evolve ways of turning off the pain-producing mechanism. Eigenbrod et al. searched RNA transcripts in eight species of subterranean rodents related to pain-resistant naked mole-rats. They found multiple changes to ion channels involved in pain across the different species. Understanding such adaptations could elucidate pain mechanisms and help us develop approaches for pain relief. Science , this issue p. 852