Re-wilding model organisms: Opportunities to test causal mechanisms in social determinants of health and aging.

Social experiences are strongly associated with individuals' health, aging, and survival in many mammalian taxa, including humans. Despite their role as models of many other physiological and developmental bases of health and aging, biomedical model organisms (particularly lab mice) remain an underutilized tool in resolving outstanding questions regarding social determinants of health and aging, including causality, context-dependence, reversibility, and effective interventions. This status is largely due to the constraints of standard laboratory conditions on animals' social lives. Even when kept in social housing, lab animals rarely experience social and physical environments that approach the richness, variability, and complexity they have evolved to navigate and benefit from. Here we argue that studying biomedical model organisms outside under complex, semi-natural social environments ("re-wilding") allows researchers to capture the methodological benefits of both field studies of wild animals and laboratory studies of model organisms. We review recent efforts to re-wild mice and highlight discoveries that have only been made possible by researchers studying mice under complex, manipulable social environments.