Abstract

Cytosine methylation lends itself for building universal epigenetic clocks that apply to all mammalian tissues and 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 including the transient application of reprogramming factors.

Genomewide association studies of epigenetic age acceleration shed light on the genetic underpinnings of the epigenetic clock. The epigenetic clock method has been used to study accelerated aging disorders (progeria, Down syndrome, overgrowth disorders) and conversely conditions that seem to be associated with slow aging (dwarf mice).

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.