ABSTRACT

Cytosine methylation lends itself for building universal epigenetic clocks that apply to all mammalian cell types and to estimate species characteristics such as maximum lifespan.

I will review what has been learnt about the mechanism underlying epigenetic clocks based on genetic and non-genetic interventions that affect epigenetic aging rates.  I will describe several rejuvenating interventions. 

I will present results from the Mammalian Methylation Consortium based on 13,000 samples derived from 348 mammalian species and 25 taxonomic orders. Positively age related cytosines are greatly enriched in polycomb repressive complex 2-binding sites, and are proximal to genes that play a role in mammalian development, cancer, human obesity, and human longevity. Methylation sites that correlated to maximum lifespan were enriched at HOX genes, indicating a link between developmental processes and maximum lifespan. Overall, these studies highlight the key role of epigenetics in the evolution of life history traits, and advance the molecular understanding of mammalian lifespan.