The primary role of hair in animals is to serve as insulation by trapping warm air against the body, and the hair coat in mammals requires a constant supply of new hairs throughout the lifetime of the animal. In humans, hair has lost most of its protective functions and now plays an important role in social interactions. For these very reasons, nature ensures that each hair follicle cyclically regenerates its lower portion that produces the hair shaft.
Hair follicle cycle
Although no new hair follicles are made postnatally, each and every hair follicle undergoes three-part cyclical growth pattern in order to produce a new hair. Normally, the hair grows to a maximum length, then hair growth ceases and the hair is shed and replaced. These phases of the hair growth cycle have been described as:
- Anagen, a long period of growth
- Catagen, the transitional period from growing to resting lasting 2 to 4 weeks
- Telogen, a period of inactivity lasting 2-4 months
Although we speak of stages in the development of a hair follicle, it should be made clear that these are actually dynamic, flowing processes and the setting up of stages is purely for our understanding of the human hair follicle cycle.
Anagen is the active phase of the hair, and extends from the termination of the inactive phase, telogen, to the beginning of the regressing phase, catagen. This phase involves the complete re-growth or regeneration of the lower, cycling portion of the follicle, i.e., the hair shaft factory. The epidermal cells surrounding the dermal papilla form the germinal matrix or root of the hair. These cells are constantly dividing, and as new cells are formed they push the older ones upwards and eventually out. During this phase the hair grows about 1 cm every 28 days. Because there is a limit to the time a follicle stays in anagen, there is also a limit to the length of its product, the hair shaft.
The anagen phase is further subdivided into six sub-stages. These are:
- Stage I -growth of the dermal papilla and on-set of mitotic activity in the germ-like overlying epithelium
- Stage II -bulb matrix cells envelop the dermal papilla and begin differentiation, evolving bulb begins descent along the fibrous streamer
- Stage III-bulb matrix cells show differentiation into all follicular components
- Stage IV-matrix melanocytes reactivate
- Stage V-hair shaft emerges and dislodges telogen hair
- Stage VI-new hair shaft emerges from skin surface
Although the sub-stages were initially described for the mouse, the same sequence of phenomena can be observed in other animals and in humans. There is generally little variation in the duration of each stage between species, except for anagen VI, which is the period during which the hair is produced at its maximum rate. The developmental processes which must occur before a hair is produced are presumably similar in all mammals.
Anagen to catagen transition
The matrix cells are referred to as transit-amplifying cells because they undergo a limited number of cell divisions before differentiating. Some molecular regulators of the anagen to catagen transition have been identified, but their exact mechanism of activity is still a grey area. Scientists have been successful in discovering that fibroblast growth factor-5 (Fgf-5) may trigger catagen onset. Mouse experiments have shown that total skin Fgf-5 expression increases in late anagen and that, in its absence, catagen induction is delayed prolonging anagen. There are other molecules that could serve as anagen-supporting signals, and there is also an increase in the number of deeply situated perifollicular mast cells. (Mast cells play an important role in the body’s allergic response).
Like anagen, catagen is a highly regulated event, in its initiation, development, and termination. The purpose of catagen is to delete the old hair shaft factory and to initiate the stem cells of the bulge and the papilla to set the stage for the formation of a new follicle. Catagen is therefore regarded as the transitional phase in the hair growth cycle, and there are chemical and structural changes that take place in the hair follicle during this phase.
The hair follicles go through a highly controlled process of involution, which is a process of progressive decline or degeneration. The involution process largely brings about a burst of programmed cell death (apoptosis) in the majority of follicular keratinocytes. Follicular melanogenesis (formation of melanin) also ceases during this stage, and some follicular melanocytes undergo apoptosis as well. Towards the end of the catagen stage, the dermal papilla condenses and moves upward, coming to rest beneath the hair-follicle bulge.
Telogen is considered as the resting stage or the period of quiescence in the hair follicle cycling process. When hair follicles enter telogen and stop making hair, they dump their last cells on to the end of the fiber. This lump of cells acts as an anchor to hold the hair fiber in the tube of the hair follicle. The hair is now called a “club” hair as the lump of cells on the end gives it a club appearance. This non living hair is attached to the skin with a “club-like” root, but will eventually be pushed out and replaced by a new growing hair, usually during combing or washing. The telogen stage typically lasts for two to three months before the scalp follicles enter the anagen stage and the cycle is repeated.
Shedding of hair is another important aspect of hair growth. As the shedding phase takes place independent of telogen and anagen, it probably utilizes a separate set of controls; and has been given a distinct name, “exogen” in hair biology. Exogen is a highly controlled and timed event in mammals that shed on a seasonal basis. This feature is a protective mechanism, which minimizes the possibility of shedding the protective fur before new fur is available. Some researchers noted that it is not unusual for human telogen hairs to be retained for more than one follicular cycle. This observation suggests that the anagen phase and the exogen phase are independent events.
The follicle stem cells
image source: https://en.wikipedia.org/wiki/Epidermis
For the purpose of regeneration of the follicle and for the maintenance of the epidermis and sebaceous gland, reservoirs of multi-potent epithelial stem cells are set aside during development. These precious follicle stem cells are found in the bulge of the hair follicle, and are activated at the telogen to anagen transition, to initiate a new round of hair growth.
Normally this cycle of hair production and inactivity continues for the duration of the individual’s life, but external factors can influence and inhibit hair production and in some cases lead to physical destruction of the hair follicle. The relative duration of each of these phases also varies with the individual’s age, nutritional status, hormonal factors, and other physiologic and pathologic factors. The duration of anagen determines the final length of the hair and thus varies according to body site; catagen and telogen duration vary to a lesser extent depending on site.
Unlike other mammals, hair growth and loss in humans is random and not seasonal or cyclic. At any given time, a random number of hairs will be in various stages of growth and shedding. Determining the molecular signals that orchestrate the follicle’s transit between these stages is one of the key challenges of hair research.