The impact of wild environment on murine epigenetic aging

The aging of mammalian epigenomes fundamentally alters cellular functions, implicating organismal fitness and disease risk. However, the studies of this process typically use mouse models in the laboratory environment and neglect the impact of variation in social, physical, microbial, and other aspects of the living environment. We examined the aging differences between lab mice and “re-wilded” mice, which are C57BL6/J mice reintroduced into a controlled field environment with enhanced realism. Systematic analysis of age-associated methylation dynamics in the liver tissues suggests a genomic region-conditioned, faster epigenetic aging rate in field mice than in lab mice, implicating a 3D genome conformation change. The predicted age of lab mice by epigenetic clocks is closer to their actual age than that of field mice. These observations underscore the overlooked role of the social and physical environment in epigenetic aging. 73 rewilded mouse liver methylome and 20 lab mouse methylome.