TY - JOUR T1 - Quantitative translation of dog-to-human aging by conserved remodeling of epigenetic networks JF - bioRxiv DO - 10.1101/829192 SP - 829192 AU - Tina Wang AU - Jianzhu Ma AU - Andrew N. Hogan AU - Samson Fong AU - Katherine Licon AU - Brian Tsui AU - Jason F. Kreisberg AU - Peter D. Adams AU - Anne-Ruxandra Carvunis AU - Danika L. Bannasch AU - Elaine A. Ostrander AU - Trey Ideker Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/19/829192.abstract N2 - Mammals progress through similar physiological stages during life, from early development to puberty, aging, and death. Yet, the extent to which this conserved physiology reflects conserved molecular events is unclear. Here, we map common epigenetic changes experienced by mammalian genomes as they age, focusing on evolutionary comparisons of humans to dogs, an emerging model of aging. Using targeted sequencing, we characterize the methylomes of 104 Labrador retrievers spanning a 16 year age range, achieving >150X coverage within mammalian syntenic blocks. Comparison with human methylomes reveals a nonlinear relationship which translates dog to human years, aligns the timing of major physiological milestones between the two species, and extends to mice. Conserved changes center on specific developmental gene networks which are sufficient to capture the effects of anti-aging interventions in multiple mammals. These results establish methylation not only as a diagnostic age readout but as a cross-species translator of physiological aging milestones. ER -