Reviewing What is Known of Hair Aging

The aging of hair is a priority for many, but in the grand scheme of things we might perhaps want to suffer that loss in preference to the decline of other bodily systems more essential to life. If that choice in priority of research and development is offered, at least. In fact, while a sizable and vocal industry focuses on the little that can be done today to satisfy the demand for an end to the aging of hair, research and development does occur, but not to the degree one might imagine, and is moving very slowly. The age-related disruption of hair growth and coloration processes is complex and incompletely understood. Even non-age-related conditions of alopecia have yet to be deciphered.

Hair follicles (HFs) are constituted by different cell types, including hair follicle stem cells (HFSCs), non-HFSC epithelial cells, immune cells, neurons, mesenchymal cells, adipocytes, and melanocytes. Other structures, such as sebaceous glands (SGs), blood vasculature, and arrector pili muscle (APM), are also important HF components. Generally, HF status depends on the hair cycle, which can be roughly divided into three stages, including anagen (the growing phase), catagen (the transition phase), and telogen (the resting phase). These phases are modulated by genes, age, microenvironment, diet, and psychological factors. HF homeostasis is disrupted due to aging, gene mutations, nutritional imbalance, hormonal dysregulation, the inflammatory microenvironment, etc., which will lead to various HF disorders such as hair aging. Although hair-related diseases are not life-threatening, they can significantly influence people's social activities and psychological wellbeing. Among these disorders, hair aging is manifested by hair graying, hair loss, hair thinning, hair follicle miniaturization (HFM), structural changes, lipid composition change, and curvature in the hair fiber. There are multiple causes of hair aging, including genetic defects, systemic diseases, ultraviolet (UV) radiation, nutritional imbalance, environmental pollution, and physical damage.

Hair aging is often accompanied by hair graying, hair loss, and hair thinning. The hair pigmentation process starts with melanocyte stem cells (McSCs), which differentiate into melanocytes to produce pigmentation units. During anagen, melanocytes go through mitosis and are activated, manifested by increasing dendricity. Through the dendrites, they can transfer melanosomes, which contain melanin. Hair graying happens when the pigmentation process is disrupted. For example, it was recently reported that McSCs could switch between transit-amplifying status and quiescence status and reside in a dynamic niche, indicating a potential role of McSC mobility in regulating cell stemness and hair graying. Hair loss, however, is mostly related to HFSC dysfunction and depletion. Physiologically, HFSCs are activated at anagen and stay quiescent at telogen. Whereas, in alopecia, HFSCs are depleted or remain in a quiescent status, leading to irreversible or reversible hair loss, respectively. HFSCs are regulated by intrinsic and extrinsic cues, such as Wnt and bone morphogenetic protein (BMP) signaling, as well as skin wounding. Hair thinning can be a transitional status before hair loss, frequently occurring with HFM, which is manifested by the reduction of the diameter of HFs and hair shaft.

Numerous theories exist about the primary mechanism underlying hair aging. The most well-known one is the thesis of oxidative stress, which accounts for multiple kinds of cell dysfunction such as mitochondrial damage and upregulated inflammatory signaling. Additionally, extensive research is being done on other possibilities, including hormone-induced premature hair aging, inflammation-predominant hair aging, and DNA damage-driven hair aging. The following sections will give detailed depictions of these concepts. In this review, we try to outline and update the signaling pathway underlying these hair aging hypotheses and provide insights into the current progress and limitations of hair aging research.