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Decoding the Science of Graying Hair


David Fisher, MD, PhD, shared pearls on fundamental biology of hair follicles, the dynamics of melanocyte stem cells, and the impact of stress on hair pigmentation.

Graying hair is a natural part of the aging process, but the mechanisms behind this phenomenon have long intrigued consumers and scientists alike. David Fisher, MD, PhD, chief of dermatology at Massachusetts General Hospital in Boston,shed light on the mechanistic aspects of graying hair and the role of melanocytes in this process at the 2024 Masterclasses in Dermatology conference. In his session “Graying and the Melanocyte: Mechanisms and Melanoma Implications,” Fisher explored the fundamental biology of hair follicles, the dynamics of melanocyte stem cells, and the impact of stress on hair pigmentation.1

Understanding the Hair Follicle Cycle

Fisher emphasized the dynamic nature of the hair follicle cycle, encompassing resting (telogen), growth (anagen), and regression (catagen) phases. The hair follicle is a complex structure consisting of permanent and transient portions. The transientportion, where melanocytes and keratinocytes collaborate, plays a crucial role in hair pigmentation.

"What is crucial about this in terms of fundamental biology, regenerative biology, is that there is a population of stem cells located at the base of the permanent portion of the hair follicle," Fisher explained.

These stem cells undergo asymmetric cell division, ensuring the replenishment of the stem cell pool. Loss of this stem cell population leads to abnormal hair growth, emphasizing the critical role they play in maintaining the hair follicle cycle.2

Genetic Engineering and Melanocyte Stem Cells

To study these intricate processes, genetic engineering was launched to tag different populations of melanocytes within the hair follicle. Fisher specifically focuses on melanocyte stem cells, demonstrating how their depletion results in premature graying in black mouse models in previous research.3 The genetic tracking of these cells reveals a depletion process linked to age, with implications for human hair aging.

Stress and Hair Graying

“If you've had any huge burst [of graying hair] because of big stress, there is a massive trigger of up regulating the pigmentation response that is mimicking the physiologic response," Fisher said

He delved into the connection between stress and hair graying. By inducing stress in mouse models, they showed a rapid depletion of melanocyte stem cells, leading to premature graying. The sympathetic nervous system, triggered by stress, plays a pivotal role in this process. The study suggests that the perception of stress, rather than the physical trigger, is crucial in initiating the depletion of stem cells.3

Therapeutic Implications and Future Research

Fisher suggested potential therapeutic avenues to prevent or reverse hair graying. He discussed the possibility of targeting β-adrenergic signaling to mitigate stress-induced hair graying, highlighting the potential application of topical approaches. “I don’t know if people would want to risk the cardiovascular effects as β blockers to prevent hair from graying,” he noted. Additionally, he touched on the intriguing link between emotional stress and clinical outcomes in melanoma patients, opening new avenues for further research in the intersection of stress and cancer therapy.4


  1. Fisher. AI in IBD: What is the Gastroenterology Perspective. Presented at: Masterclasses in Dermatology February 16-19, 2024; Puerto Rico.
  2. Doctrow B. Aging melanocyte stem cells and gray hair. National Institutes of Health. May 2, 2023. Accessed February 18, 2024. https://www.nih.gov/news-events/nih-research-matters/aging-melanocyte-stem-cells-gray-hair
  3. Iida M, Tazaki A, Yajima I, et al. Hair graying with aging in mice carrying oncogenic RET. Aging Cell. 2020;19(11):e13273. doi:10.1111/acel.13273
  4. Cybulla E, Vindigni A. Leveraging the replication stress response to optimize cancer therapy. Nat Rev Cancer. 2023;23(1):6-24. doi:10.1038/s41568-022-00518-6
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