Summary
Hair graying is a universal hallmark of aging1 but its mechanisms are insufficiently understood2 and its reversibility in humans remains uncertain. Moreover, while psychological stress accelerates human biological aging3,4and triggers hair graying in animals5, no prior study has longitudinally examined the stress-to-hair graying connection in humans. Here we develop an approach to quantitatively profile natural graying events and their associated proteomic signatures along individual human hairs, resulting in a quantifiable physical timescale of aging. Using this approach, we identify white hairs that naturally regain pigmentation within days to weeks in healthy young individuals across sex, ethnicities, ages, and body regions, demonstrating that human hair graying is naturally reversible. Proteomic analysis of matched dark and white hairs replicated across two independent experiments show that graying is marked by the upregulation of proteins related to energy metabolism, mitochondria, and antioxidant defenses. Coordinated graying and reversal also occur simultaneously across multiple scalp hair follicles of a person, suggesting that unknown systemic factors influence hair graying patterns. Combining hair pigmentation profiling and proteomics at the single hair shaft level, we also report hair graying and reversal occurring in parallel with behavioral and psychological stressors. A computational simulation of life-long and stress-induced hair graying suggests a threshold-based mechanism for the rapid reversibility of graying. Together, these findings document the reversibility of hair graying in humans and provide a new model to examine the modifiability of human aging.
Competing Interest Statement
The authors have declared no competing interest.
