Graying hair has long been considered a one-way street. A stubborn, visible reminder that aging starts well before we feel it. But new findings from researchers at NYU Langone Health suggest that this biological marker might be reversible—not with cosmetic dyes, but through targeted stem cell intervention.
In a landmark study published in Nature, scientists discovered that the process of graying is not necessarily the result of pigment loss, stem cell exhaustion, or aging per se. Instead, the underlying cause may be a failure of melanocyte stem cells (McSCs) to relocate within the hair follicle as needed during the hair growth cycle.
The finding reframes gray hair as a logistical malfunction, rather than a permanent biological decline. As McSCs become stuck in the wrong part of the follicle, they miss critical molecular cues required for producing melanin—the pigment responsible for hair color.
A commute problem, not a cellular shutdown
At the center of this research are melanocyte stem cells, specialized cells responsible for regenerating melanocytes, the pigment-producing cells in hair. These McSCs live in a region of the follicle called the bulge, which is typically a stem-cell “safe zone” with no active signaling for pigment production.
As each new hair begins to grow, the McSCs must migrate from the bulge to the hair germ region, where exposure to WNT signaling proteins triggers them to mature into melanin-producing cells. But in aging mice—or mice subjected to repeated hair removal—researchers found that increasing numbers of McSCs failed to migrate out of the bulge. They stayed put, and the growing hair remained unpigmented.
“It is the loss of chameleon-like function in melanocyte stem cells that may be responsible for graying and loss of hair color,” said Dr. Mayumi Ito, professor at NYU’s Ronald O. Perelman Department of Dermatology and Department of Cell Biology, and senior investigator on the study.
This failure was not due to cellular aging or damage. In fact, the stem cells were still viable. They simply weren’t in the right place at the right time to receive the WNT signal that initiates pigment production.
Why WNT signaling matters—and how it could guide therapies
The WNT/β-catenin signaling pathway plays a critical role in both stem cell activation and differentiation. When McSCs enter the WNT-rich hair germ zone, they are prompted to transform into pigment-producing melanocytes. But if they remain in the WNT-suppressed bulge, they stay inactive and colorless.
This aligns with existing research on WNT’s centrality to epidermal stem cell function, including a Med Sci (Paris) that found WNT signaling essential for maintaining the identity, proliferation, and differentiation of hair follicle stem cells.
In the Nature study, the team demonstrated that persistent WNT activation in cells can push them toward terminal differentiation, while its suppression allows some partially mature McSCs to revert to a stem-like state. This dynamic ability—known as dedifferentiation—gives McSCs a rare plasticity that could be harnessed in future therapies.
Importantly, not all McSCs retain this flexibility. The longer they remain mispositioned in the bulge, the less likely they are to contribute to pigment regeneration in subsequent hair cycles. In aging follicles, researchers observed a progressive accumulation of these stranded stem cells.
Dedifferentiation offers a new path forward
The NYU researchers went further by genetically labeling a late-stage pigmentation gene, Oca2, and tracking its activity in McSCs. They found that even Oca2-positive cells—typically considered committed to a pigment-producing fate—could reverse course and return to an undifferentiated, stem-like state if relocated to a low-WNT environment.
This ability to shuttle between compartments and shift identities underscores the plastic nature of McSCs, but also highlights the system’s vulnerability. When the internal commute breaks down, stem cells remain viable but functionally lost.
“The newfound mechanisms raise the possibility that the same fixed positioning of melanocyte stem cells may exist in humans,” said Qi Sun, PhD, postdoctoral fellow at NYU Langone and lead author of the study. “If so, it presents a potential pathway for reversing or preventing the graying of human hair by helping jammed cells to move again between developing hair follicle compartments.”
Implications for regenerative medicine
While there’s no drug or treatment yet to reset McSC location or WNT signaling in human hair follicles, this study lays out a biological blueprint that could guide next-generation interventions. Restoring McSC movement—rather than simply activating dormant cells—may be key to reversing graying without disrupting follicle function or depleting stem cell reserves.
The implications may stretch well beyond hair color. If stem cell misplacement contributes to functional decline in hair follicles, it may also underlie other age-related tissue dysfunctions where timing and location—not cell death—drive degeneration.