Summary
Hair graying is a universal hallmark of chronological and biological aging, but its mechanisms are insufficiently understood and its potential reversibility in humans has not been quantitatively examined. Moreover, while psychological stress accelerates human biological aging and triggers hair graying in animals, no prior study has longitudinally examined the stress-to-hair graying connection in humans. Here we develop a novel approach to quantitatively profile natural graying events and their associated proteomic signatures along individual human hair shafts, resulting in a quantifiable physical timescale of hair pigmentation patterns (HPPs). Using this approach, we quantify rare events of white/gray hairs that naturally regain pigmentation within days to weeks, in 14 individuals across sex, ethnicities, ages, and body regions, thereby quantitatively defining the reversibility of graying across hairs in healthy, unmedicated individuals. Proteomic analysis of matched dark (i.e. pigmented) 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. Combining hair pigmentation profiling and proteomics at the single hair level, we also report hair graying and its 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 episodic instability of HF pigmentation and the temporary reversibility of graying. Our results show how quantitatively mapping HPPs in humans can provide an opportunity to examine the modifiability of biological aging in relation to life exposures.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
