Unraveling hair graying: insights into melanocyte biology and the aging process

Melanogenesis and pigmentation are crucial processes for normal skin and hair, and they are regulated by complex factors. Unlike epidermal pigmentation, follicular melanogenesis depends on cyclic replenishment from a bulge melanocyte stem cell reservoir, making its functional decline generally irreversible yet clinically reversible under rare conditions. Herein, we systematically review the core biological processes governing follicular pigmentation, including embryonic specification, niche homing, cyclic lineage migration, and microenvironmental signaling networks. We further integrate emerging single-cell and spatial omics findings to propose a novel, three-stage chronological model of canities, bridging mouse-derived mechanisms with human clinical evidence. There are multiple conditions that lead to hair graying, such as aging, premature hair graying, the stem cell niche environment, and the biological variety of melanocytes and hair follicles, with aging being the most common factor among these. In brief, the exact mechanisms of hair pigmentation and depigmentation remain elusive. Herein, we review the physiology and pathology of hair pigmentation and depigmentation, and summarize the mechanisms that might be affected during human hair graying.