Why Does Stress Cause Hair Loss?
Restore Hair and Scalp- May 14
- 5 min read
When the body is undergoing stress, it signals the sympathetic nervous system (SNS), also known as our “fight or flight” response. Once activated, the SNS causes the adrenal medulla to release stress hormones called catecholamines (mainly norepinephrine and epinephrine) into the bloodstream. These hormones bind to receptors throughout the body, triggering several physiological changes that prepare the body to respond to danger. Once the threat has dissipated, the parasympathetic nervous system then works to help our bodies return to a calm, resting state. But, what happens when the body remains in a stressed state? Stress, whether from a traumatic event or a sustained period, can lead to hair loss. This connection between stress and hair loss will be the focus of today.
Stress-related hair loss involves a complex interplay between the nervous system, endocrine signals, and immune cells, particularly macrophages and mast cells. Macrophages and mast cells are innate immune cells, otherwise known as the cells that provide the first line of defense against infections and other threats. Some types of macrophages contribute to hair loss by polarizing into an inflammatory state and response, when under stress. These are signaled through catecholamines (noradrenaline/norepinephrine) into the bloodstream. Other macrophage subsets, signal to the Hair Follicle Stem Cells, to remain dormant during the telogen (resting) phase of the hair cycle,which prevents premature activation of hair follicle stem cells and thus delays the entry of hair follicles into the growth phase (anagen). This controlled dormancy preserves stem cell function and ensures proper hair cycle progression, which ultimately supports healthy, cyclical hair growth. Temporarily inhibiting this pathway can promote hair growth by allowing hair follicle stem cells to activate sooner.
Mast cells are well known for their roles in allergic reactions and inflammation. They also have important physiological functions, including hair regrowth. In some studies, researchers have used mouse hair follicles as a model for how organs naturally shrink and remodel themselves and they studied how mast cells changed in the differing phases of the hair growth cycle. Their research suggests that mast cells act as “control switches” for tissue remodeling, and when used for hair growth, mast cells can tell the hair follicle when to stop growing and start shrinking and this regulation is essential for a healthy hair cycle. Balanced cycling is crucial for sustained, healthy hair growth over time. During the transition from resting (telogen) to growth (anagen) phase in hair follicles, the number of mast cells in the skin decreases sharply due to their activation and release of substances (degranulation). This process appears to stimulate hair growth.
Cortisol is a hormone produced when we are stressed and is also linked to hair loss. When stressed, the cortisol activates the mast cells and creates an inflammatory environment that is detrimental to hair growth. When mast cells are activated through stress, it creates an inflammatory environment around hair follicles, disrupts their normal function, damages stem cells, and promotes hair shedding, often resulting in hair loss disorders such as Telogen Effluvium. Mast cells also link the nervous and immune systems in hair regulation. They are located near sensory nerve endings in the skin, and neuropeptides like substance P (SP) can degranulate mast cells, leading to the release of cytokines and nerve growth factors (NGF). Studies have shown that stress increases the number of mast cells and their activation near hair follicles, and blocking the receptors involved in this nerve-mast cell signaling can prevent stress-induced hair loss. This “brain-hair follicle axis” highlights mast cells as critical mediators linking psychological stress to hair follicle dysfunction and hair loss.
Macrophages, a type of specialized white blood cell, are essential to the body's innate immune response. Their primary function is phagocytosis, a process where they engulf and digest harmful microbes, dead cells, and cellular debris.They also release signaling molecules called cytokines that help coordinate immune responses, recruit other immune cells, and promote inflammation to fight infections. Macrophages are crucial immune cells found in almost all tissues. They are vital for both defending the body against infection and maintaining tissue health. These cells release signaling molecules called cytokines, which coordinate immune responses, attract other immune cells, and promote inflammation to combat infections. In addition to their defensive roles, macrophages are involved in tissue repair and remodeling. Their behavior adapts to their surroundings, allowing them to take on inflammatory (M1) or healing (M2) functions.
Resident perifollicular macrophages (pfMACs) are crucial immune cells residing near hair follicles, playing a key role in regulating hair growth. Their numbers and location change dynamically throughout hair follicle development and growth cycles.
Prior to a new growth phase, a subset of pfMACs undergo apoptosis, releasing Wnt signaling molecules that activate dormant hair follicle stem cells, initiating new hair growth.
Disruption of this process, either through a failure of pfMACs to die or an inability to release Wnts, results in delayed hair growth, underscoring the importance of pfMAC-derived Wnts in hair regeneration.
Furthermore, pfMACs secrete growth factors that influence the termination of hair growth and the onset of follicle regression. This precisely timed release of factors enables pfMACs to manage the hair growth cycle and maintain hair follicle health.
The activity of pfMACs is sensitive to their local environment, including metabolic and immune signals. These environmental cues influence their capacity for tissue repair, their role in protecting hair follicles from immune system attacks, and their potential contribution to inflammatory conditions or hair loss.
Perifollicular macrophages (pfMACs) are also involved in angiogenesis, the formation and remodeling of blood vessels surrounding hair follicles. This vascular support ensures that hair follicles receive adequate nutrients necessary for robust hair growth.
Finally, pfMACs collaborate with other immune cells, such as mast cells, to modulate the behavior of hair follicle stem cells and ultimately control the process of hair growth.
Perifollicular macrophages (pfMACs) play an important role in turning on hair follicle stem cells and controlling the hair growth cycle. They do this by releasing special signals like Wnts and growth factors, and by changing their behavior based on their surroundings. Because of this, pfMACs are key to healthy hair growth and could be good targets for treating hair loss.
In summary, stress activates the sympathetic nervous system, releasing hormones that prepare the body for immediate action but, when prolonged, can negatively impact hair growth. This stress response involves complex interactions between the nervous system, hormones like cortisol, and immune cells-particularly macrophages and mast cells-that play crucial roles in regulating the hair cycle. Macrophages near hair follicles help control stem cell activation and hair growth by releasing signals such as Wnts and growth factors, while also responding to the local environment to either promote healing or inflammation. Mast cells act as regulators that signal hair follicles when to stop growing and start shrinking, but under stress, their increased activation creates inflammation that damages hair follicles and disrupts normal hair cycling. Together, these immune cells form a critical link between stress and hair loss, highlighting potential targets for therapies aimed at preventing or reversing stress-related hair disorders. Understanding how macrophages and mast cells influence hair follicle behavior deepens our knowledge of hair biology and opens new avenues for treating hair loss caused by stress.
References
Maurer, M., Paus, R., & Czarnetzki, B. M. (1995). Mast cells as modulators of hair follicle cycling. Exp Dermatol, 4(4 PT 2), 266-71. 10.1111/j.1600-0625.1995.tb00256.x.
Muneeb, F., Hardman, J. A., & Paus, R. (2019). Hair growth control by innate immunocytes: Perifollicular macrophages revisited. Exp Dermatol, 28(4), 425-431. 10.1111/exd.13922
Paus, R., Maurer, M., Slominski, A., & Czarnetzki, B. M. (1994). Mast cell involvement in murine hair growth. Dev Biol, 163(1), 230-40. 0.1006/dbio.1994.1139
Shin, H., Choi, S.-J., Cho, A.-R., Kim, D. Y., Kim, K. H., & Kwon, O. (2016). Acute Stress-Induced Changes in Follicular Dermal Papilla Cells and Mobilization of Mast Cells: Implications for Hair Growth. Ann Dermatol, 28(5), 600-606. 10.5021/ad.2016.28.5.600
Wang, E. C. E., Dai, Z., Ferrante, A. W., Drake, C. G., & Christiano, A. M. (2019). A Subset of TREM2+ Dermal Macrophages Secretes Oncostatin M to Maintain Hair Follicle Stem Cell Quiescence and Inhibit Hair Growth. Cell Stem Cell, 24(4), 654-669. 10.1016/j.stem.2019.01.011
