Enigma World Aging Center

ENIGMA’s Epigenetics Working Group, currently lead by Sylvane Desrivières, relates DNA methylation levels at Cytosine-phosphate-Guanine sites (CpGs) across the genome to brain metrics in 10,000+ people, to discover epigenetic markers of accelerated brain aging. Our group has discovered two epigenetic DNA methylation loci promoting brain aging in pilot studies. Each person’s “epigenetic age” will be computed using the Horvath clock (Horvath 2013) based on 353 age-susceptible CpGs sites; this epigenetic clock predicts all-cause mortality and poorer physical and cognitive performance (Marioni 2015 a,b). We will supplement it with our own epigenetic risk score based on our highly powered brain epigenome-wide association study (EWAS).

QUESTIONS

Does epigenetic age predict brain metrics better than simple biological age? Is this true only in older individuals (>age 70) or throughout life? Do the epigenetic clock and brain age jointly predict clinical decline better than each metric alone?

ONGOING PROJECT

Genome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes. We expect to publish the world’s first epigenetic study of hippocampal volume, reporting DNA methylation differences predicting volume differences in over 3,000 people.