Universal DNA methylation age across mammalian tissues

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.Publisher PDFPeer reviewe

Universal DNA methylation age across mammalian tissues.

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

Non-native phonemes in adult word learning: evidence from the N400m

Newborns are equipped with a large phonemic inventory that becomes tuned to one's native language early in life. We review and add new data about how learning of a non-native phoneme can be accomplished in adults and how the efficiency of word learning can be assessed by neurophysiological measures. For this purpose, we studied the acquisition of the voiceless, bilabial fricative /Φ/ via a statistical-learning paradigm. Phonemes were embedded in minimal pairs of pseudowords, differing only with respect to the fricative (/aΦo/ versus /afo/). During learning, pseudowords were combined with pictures of objects with some combinations of pseudowords and pictures occurring more frequently than others. Behavioural data and the N400m component, as an index of lexical activation/semantic access, showed that participants had learned to associate the pseudowords with the pictures. However, they could not discriminate within the minimal pairs. Importantly, before learning, the novel words with the sound /Φ/ showed smaller N400 amplitudes than those with native phonemes, evidencing their non-word status. Learning abolished this difference indicating that /Φ/ had become integrated into the native category /f/, instead of establishing a novel category. Our data and review demonstrate that native phonemic categories are powerful attractors hampering the mastery of non-native contrasts