The epigenetics of frailty.

The conceptual change of frailty, from a physical to a biopsychosocial phenotype, expanded the field of frailty, including social and behavioral domains with critical interaction between different frailty models. Environmental exposures - including physical exercise, psychosocial factors and diet - may play a role in the frailty pathophysiology. Complex underlying mechanisms involve the progressive interactions of genetics with epigenetics and of multimorbidity with environmental factors. Here we review the literature on possible mechanisms explaining the association between epigenetic hallmarks (i.e., global DNA methylation, DNA methylation age acceleration and microRNAs) and frailty, considered as biomarkers of aging. Frailty could be considered the result of environmental epigenetic factors on biological aging, caused by conflicting DNA methylation age and chronological age.