Gray Hair: From Preventive to Treatment

Abstract

Aging is an inevitable natural process, with gray hair being one of its most visible signs. Hair graying holds psychosocial importance and is an excellent model for studying human pigmentation and aging in an accessible mini-organ. This phenomenon results from decreased melanin production in hair follicles, influenced by genetic, environmental, and lifestyle factors. Gray hair often poses aesthetic concerns and can be accelerated by environmental stressors, lifestyle choices, and nutritional deficiencies. Given the variation in onset and prevalence of gray hair, this study explores the underlying biological factors-namely, genetics, oxidative stress, and hormonal changes-to inform better prevention and treatment strategies. Recent advancements in prevention and treatment, such as topical melanin stimulants, antioxidants, dietary supplements, and low-level laser therapy (LLLT), offer promising approaches to managing gray hair. Understanding gray hair comprehensively-encompassing biological, psychological, and social dimensions-provides valuable insights into the aging process and can enhance overall well-being while addressing the stigma associated with aging. Our comprehensive analysis reveals that while graying correlates with certain health conditions, its primary significance is physiological rather than pathological. This understanding is essential for healthcare providers and the public to approach graying with scientific objectivity rather than social prejudice.

Keywords: aesthetic; aging; curative; hair graying; oxidative stress; preventive.

Figure 1

Schematic structure of the hair and regulators of human hair follicle pigmentation. Multiple positive (indicated by arrows) and negative (indicated by inhibitor lines) factors regulate human hair follicle pigmentation. Reprinted from Ageing Res Rev, volume 89, Wang S, Kang Y, Qi F, Jin H. Genetics of hair graying with age. 101977, copyright 2023, with permission from Elsevier.

Figure 2

Main genes and molecular signaling pathways involved in melanogenesis from expression studies. Melanogenesis is the biosynthesis of melanin within melanosomes by a series of reactions. The process is initiated from either the hydroxylation of L-phenylalanine to L-tyrosine by phenylalanine hydroxylase (PAH), which is the nonobligatory step, or directly from L-tyrosine. And then L-tyrosine is hydroxylated to L-dihydroxyphenylalanine (L-DOPA) catalyzed by tyrosinase, which is the crucial rate-limiting step in melanin biosynthesis. The next step is the oxidation of L-DOPA to dopaquinone, and dopaquinone is then processed into pheomelanin in the presence of thiols, or eumelanin in the absence of thiols. Subsequently, the melanosomes containing melanin are successively transferred from melanocytes and incorporated into keratinocytes, thus generating hair pigmentation. Paracrine factors including α-MSH, ACTH, ASP, SCF, ET-1, and WNT secreted by fibroblasts and keratinocytes, bind to their corresponding receptors, and then activate multiple signaling pathways. Sequentially, the transcription of MITF is promoted, which contributes to promoting expressions of key genes related to melanogenesis such as TYR, TYRP1, DCT, Rab27a, MLPH, and MYO5A. Therefore, melanin is synthesized by elevated key enzymes, initiated from tyrosine to L-DOPA catalyzed by TYR. The next step is the oxidation of L-DOPA to dopaquinone, and dopaquinone is then processed into pheomelanin or eumelanin. With the help of transport proteins such as Rab27a, MLPH, and MYO5A, melanosomes containing abundant melanin are transported from melanocytes to keratinocytes. Reprinted from Ageing Res Rev, volume 89, Wang S, Kang Y, Qi F, Jin H. Genetics of hair graying with age. 101977, copyright 2023, with permission form Elsevier.

Figure 3

Stress Induces Depletion of MSCs by Sympathetic Nerve Activation Hair follicles undergo physiological cycles of regeneration. Each hair cycle produces a keratinized hair fiber, with color derived from pigment mature melanocytes produce. In mice, stress activates sympathetic nerves, releasing noradrenaline in the MSCs’ niche. This results in MSCs depletion, and subsequent hair growth lacks color due to the absence of new melanocyte production. Reprinted from Dev Cell, volume 52(5), Huang S, Rompolas P. The psychology of gray hair. 548–549, copyright 2020, with permission from Elsevier.