Hair graying is a common sign of aging resulting from complex regulation of melanogenesis. Currently, there is no medical treatment available for hair repigmentation. In this article we review the literature on medication-induced hair repigmentation, discuss the potential mechanisms of action, and review the quality of the literary data. To date, there have been 27 studies discussing medication-induced gray hair repigmentation, including 6 articles on gray hair repigmentation as a primary objective, notably with psoralen treatment or vitamin supplementation, and 21 reports on medication-induced gray hair repigmentation as an incidental finding. Medications noted in the literature include anti-inflammatory medications (thalidomide, lenalidomide, adalimumab, acitretin, etretinate, prednisone, cyclosporin, cisplatinum, interferon-α, and psoralen), stimulators of melanogenesis (latanoprost, erlotinib, imatinib, tamoxifen, and levodopa), vitamins (calcium pantothenate and <i>para</i>-amino benzoic acid), a medication that accumulates in tissues (clofazimine), and a medication with an undetermined mechanism (captopril). Diffuse repigmentation of gray hair can be induced by certain medications that inhibit inflammation or stimulate melanogenesis. There is also low-quality evidence that some vitamin B complex supplementation can promote gray hair darkening. While these compounds are not currently indicated for the treatment of gray hair, their mechanisms shed light on targets for future medications for hair repigmentation.

ABSTRACT Background Hair graying is an age‐associated condition primarily caused by the depletion and dysfunction of melanocyte stem cells within hair follicles. Emerging regenerative strategies, including exosome‐based therapies, offer the potential to restore pigmentation by targeting underlying cellular mechanisms. Objective To investigate the clinical outcomes and correlates of hair repigmentation following exosome‐based therapy in individuals with gray hair. Methods This cross‐sectional observational study enrolled 10 patients with visible gray or white hair who were treated with rose stem cell‐derived exosomes (RSCEs) using various procedures. Gray hair repigmentation outcomes were assessed using a standardized scale. Statistical correlations between clinical variables and treatment responses were analyzed. Results A mean of 4.6 ± 1.3 treatment sessions was performed. Repigmentation was observed after an average of 2.4 ± 0.7 sessions and was maintained for 4.7 ± 1.9 months. The various treatment modalities also demonstrated efficacy in both hair regrowth and hair repigmentation. The mean outcome score was 2.8 ± 0.78, with 60% achieving a higher‐grade response (≥ 50% improvement). Shorter duration of graying ( p = 0.0363), presence of androgenetic alopecia (AGA) ( p = 0.0332), and moderate baseline severity (Stage 2) ( p = 0.0133) were significantly associated with better outcomes. No adverse events were reported. Conclusion Exosome‐based therapy appears to be a safe and 7 11 2025 24 11 e70526 e70526 8 11 2025 © 2025 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ABSTRACT Background Hair graying is an age‐associated condition primarily caused by the depletion and dysfunction of melanocyte stem cells within hair follicles. Emerging regenerative strategies, including exosome‐based therapies, offer the potential to restore pigmentation by targeting underlying cellular mechanisms. Factors such as the presence of AGA, shorter duration of graying, and moderate baseline severity may predict a better response. Larger, controlled studies are warranted to validate these findings and help standardize treatment protocols. Keywords: androgenetic alopecia, exosomes, gray hair, hair repigmentation, rose stem cell exosomes status released display-pdf yes is-in-collection-domain yes is-olf no is-manuscript no is-preprint no is-journal-matter no is-scanned no is-retracted no Revised 2025 Oct 11; Received 2025 Jul 28; Accepted 2025 Oct 17; Issue date 2025 Nov. 1. Introduction Hair graying is a common, age‐associated process primarily driven by the depletion, dysfunction, and migration failure of melanocyte stem cells (MeSCs) within the hair follicle niche [ 1 ]. These changes are exacerbated by intrinsic and extrinsic factors such as oxidative stress [ 2 ], mitochondrial DNA damage, inflammation [ 3 ], and niche aging, leading to an irreversible loss of pigment production in the hair shaft [ 4 ]. Although cosmetic dyes offer temporary coverage, they do not address the underlying pathophysiology and may cause allergic reactions or scalp irritation with repeated use [ 5 ]. Due to the lack of a standardized scale to determine hair graying severity and treatment response in the current literature, we employed the hair graying scale [ 11 ]—a standardized percentage‐based gray hair grading system—evaluated by two blinded dermatologists. This grading system classifies graying into five categories based on the estimated percentage of gray hair present. Grade 0 indicates no visible graying (0%), while Grade 1 corresponds to mild graying involving 1%–25% of the scalp hair. Moderate graying, defined as 26%–50% involvement, is categorized as Grade 2. duration (m), duration of visible repigmentation from the last treatment; Repig. onset (sessions), repigmentation first seen (sessions); RF microneedling, fractional RF microneedling; Thulium laser, fractional 1927 nm thulium laser; Topical, topical application; wk, Frontal views at baseline (A) and after 16 weeks of four sessions at 4‐week intervals (B) show increased darkening and density of the frontal hairline. Left lateral views before (C) and after treatment (D) demonstrate significant pigment restoration of temporal gray hair. Vertex views at baseline (E) and after treatment (F) reveal visible darkening of gray hair and improved coverage. FIGURE 6 Case 3: Hair repigmentation after six treatment sessions at 4‐week intervals using fractional 1064‐nm Nd: YAG picosecond laser combined with electroporated exosome delivery. This leads to impaired melanocyte activation and contributes to the hair graying observed in AGA. Exosome therapies that restore signaling and improve the scalp microenvironment may help reactivate these MeSCs and enhance pigmentation outcomes [ 18 , 19 ]. Another key determinant of repigmentation efficacy was the duration of gray hair, with shorter durations (< 10 years) associated with significantly better outcomes ( p = 0.0363). This finding supports previous hypotheses that the likelihood of repigmentation diminishes over time due to progressive MeSCs depletion and irreversible follicular miniaturization [ 20 , 21 ]. This study provides preliminary groundwork, but larger‐scale trials are required to standardize exosome source, dosage, delivery method, and frequency, as well as to identify molecular predictors of response. Long‐term follow‐up is also necessary to assess the durability of repigmentation and the need for maintenance treatments. 6. Conclusion This cross‐sectional observational study provides preliminary clinical evidence supporting the efficacy of exosome‐based therapy in inducing hair repigmentation in individuals with gray hair, utilizing various treatment techniques.

Hair pigmentation is a complex biological process regulated by the number and activity of melanocytes in the hair follicle. Although the classical understanding of hair graying is that the aging process is the primary factor, modern research increasingly suggests that psychological and physiological stress also significantly contribute to premature depigmentation. Objective: This study aimed to analyze the biological mechanisms by which stress affects hair pigmentation, with a focus on the neural regulation of melanocyte stem cells. Methods: A mechanistic research approach was applied using a systematic review of experimental and translational studies published between 2000 and 2025. The emphasis was on neurobiological, cellular, and molecular data describing stress-induced changes within the hair follicle. Results: The study shows that stress activates the sympathetic nervous system, leading to excessive release of norepinephrine in hair follicles. This signal induces premature differentiation and depletion of melanocyte stem cells (McSCs), resulting in irreversible hair depigmentation. These results support the idea that stress-induced hair graying is a neurobiological process of aging and not a purely cosmetic or chronological phenomenon. A detailed overview of the processes may contribute to the development of future preventive or therapeutic strategies. * Corresponding author: Hanna Boiko. Copyright © 2026 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. Impact of stress on hair pigmentation: Neurobiological depletion of melanocyte stem cells Hanna Boiko * Hair color researcher/Health hair recovery specialist, Sheisart LLC, Charlotte, NC, 28277, USA. World Journal of Biology Pharmacy and Health Sciences, 2026, 25(03), 058-061 Publication history: Received on 01 January 2026; revised on 14 February 2026; accepted on 17 February 2026 Article DOI: https://doi.org/10.30574/wjbphs.2026.25.3.0104 Abstract Hair pigmentation is a complex biological process regulated by the number and activity of melanocytes in the hair follicle. Although the classical understanding of hair graying is that the aging process is the primary factor, modern research increasingly s uggests that psychological and physiological stress also significantly contribute to premature depigmentation. Objective: This study aimed to analyze the biological mechanisms by which stress affects hair pigmentation, with a focus on the neural regulation of melanocyte stem cells. Methods: A mechanistic research approach was applied using a systematic review of experimental and translational studies published between 2000 and 2025. The emphasis was on neurobiological, cellular, and World Journal of Biology Pharmacy and Health Sciences, 2026, 25(03), 058-061 60 3.2. Depletion of Melanocytic Stem Cells Experimental data indicate that elevated norepinephrine concentrations cause premature activation of McSCs, stimulating their accelerated proliferation and differentiation [4]. This process disrupts the physiological state of cellular quiescence and leads to rapid depletion of the stem cell population. Following the loss of McSCs, the hair follicle loses the ability to form new pigment-producing melanocytes, which clinically manifests as persistent hair graying [1,7]. 3.3. Independence from Endocrine and Immune Pathways Studies in models with adrenal insufficiency and immune cell deficiency have shown the persistence of stress -induced hair graying [4,5]. This confirms that stress hormones (cortisol) and immune mechanisms are not the leading factors in hair depigmentation under stress. A summary of stress -related neural and cellular pathways involved in hair depigmentation is provided in Table 1. Table 1 Key stress-related pathways involved in hair follicle depigmentation Stress mediator Target cell Molecular mechanism Effect on pigmentation Reference Sympathetic nerve activation Hair follicle stem cell niche Stress-induced neural signaling disrupts McSCs quiescence Progressive depletion of pigment-producing cells [4,5] Reactive oxygen species (ROS) Melanocytes Oxidative damage to melanosomes and melanogenic enzymes Reduced melanin synthesis [2,10] Cortisol Melanocytes Modulation of melanogenesis-related gene expression Minimal direct effect on pigmentation [4,5] Inflammatory cytokines (IL -6, TNF-α) Melanocytes Inhibition of tyrosinase activity and melanocyte survival Hypopigmentation [10,11] DNA damage response signaling McSCs Stress-induced genotoxic stress Permanent depigmentation [1,7,8] Aging-associated pathways Hair follicle pigmentary unit Reduced McSCs self -renewal capacity Gradual hair graying [3,7,8] 3.4. Irreversibility of Pigmentation Loss Unlike pigmentation disorders associated with age -related, inflammatory, or metabolic processes, stress -induced depigmentation is characterized by irreversibility due to the structural destruction of some McSCs [7,8]. The accelerated depigmentation process associated with acute or chronic stress has been proven and studied by the author of this work not only based on scientific literature but also through many years of personal experience in the field of hair coloring and restoration. 4. Conclusion Stress-induced hair graying is caused by activation of the sympathetic nervous system and subsequent depletion of melanocyte stem cells. This process is independent of hormonal and immune stress response pathways and leads to irreversible pigment loss. The se findings advance our understanding of hair aging mechanisms and highlight the importance of neural regulation in maintaining skin homeostasis. Understanding the specifics of stress -induced depigmentation will enable practicing hair restoration and color specialists to select the most appropriate formulations and care products for prematurely grayed hair.

Hair symbolizes well-being and self-expression, with graying occurring naturally among different racial groups at varying ages. Premature graying has psychological and societal impacts, influencing self-esteem and quality of life. Gray hair usually advances gradually and is permanent, with occasional reports of natural repigmentation. Premature graying of hair (PMGH) results from a complex interplay of genetic, environmental, and cellular factors. Studies exploring links between gray hair and conditions such as osteopenia, hearing loss, smoking, obesity, dyslipidemia, and cardiovascular disease have yielded mixed results. Despite continuous research into the causes of gray hair, effective, evidence-based treatments are lacking and still need to be improved. Herein, we reviewed the causes, mechanisms, risk factors, psychosocial effects, and emerging therapies for PMGH.