Our Genetic Hair Heritage
Scalp and body hair serve no apparent purposes that are essential to our survival or to our physical well-being. So, why do we have hair?
Humans belong to the class of warm-blooded life-forms called mammals. Mammals are characterized by (1) having hair, and (2) bearing live young and suckling their young in infancy. Body hair is as characteristic of mammals as feathers are of birds and scales are of fish. The hair that grows from our body and scalp is a genetic heritage of mammalian ancestry.
Human hair may have had a survival benefit in the past-perhaps as an insulator against excessive heat or cold. Today, the function of human hair is largely cultural and psychosocial. Recent scientific findings indicate that stem cells in hair follicles may have a functional role in wound repair.
Scientists have identified most of the genes involved in hair growth and hair loss. “Tweaking” of the genes in laboratory animals can produce animal models for hair loss such as nude mice. But, not enough is yet known to “tweak” genes in humans to prevent hair loss or to regrow lost hair.
The genes involved in hair follicle development have been around for a long time in mammals and other life forms, indicating the tendency for nature to use and re-use genes that have proven successful. Much of the genetic apparatus of hair follicle development has been found in fruit flies and in mice and the genes given often fanciful names by the scientists who discovered them-for example, the gene hairless found in both mice and humans.
The genetic heritage of one’s family-parents, uncles, aunts, etc.-often determines whether male-pattern or female-pattern hair loss traits are expressed in one’s own body. and Hair Loss and Its Causes).
A clear difference between cyclic hair loss and growth in humans and in some other mammals is (1) the linkage of hair loss/regrowth to season and environment in some mammals, and (2) the cyclic loss and regrowth of hair in humans. In animals, the seasonal hair loss and regrowth is called “molting”. Human cyclic hair loss and regrowth may have had its origins in a mammalian past, but the human pattern of anagen (growth)-catagen (degradation)-telogen (rest) is not seasonal and is not known to be significantly affected by environmental factors such as ambient temperature or solar radiation.
The Hair Follicle
The human hair follicle is a tiny biological factory for the production of hair. It has a complex anatomical structure and a complex physiological function that is conducted under the influence of genetic and hormonal controls. Like any factory, it has a limited effective lifetime: each follicle completes 10 to 20 anagen-catagen-telogen cycles in its lifetime-or said another way, each follicle produced 10 to 20 hairs in its lifetime. Completion of each scalp hair cycle can take from 2 to 8 years.
Anatomy of the Hair Follicle
The hair follicle, whether it is on the scalp or elsewhere on the body, has a characteristic anatomical structure:
- In overall shape, the follicle is a slim, hollow shaft extending from the surface of the skin into layers of underlying skin and fat cells. The scalp hair follicle sits at a slant in the skin, not at a 90-degree vertical angle; thus, hair grows out of follicles at a slant in relation to the scalp, not straight up like bristles in a brush. There are about 5 million hair follicles on a human, of which about 1 million are on the head and 100,000 to 150,000 on the scalp.
- In cross-section view, the follicle is seen to be organized in concentric compartments. The outermost layer of cells is the outer root sheath, beneath it the inner root sheath and then the hair shaft. The hair shaft itself has three concentric compartments: the outermost cuticle, the underlying cortex and the innermost medulla.
- Longitudinally, the follicle is anatomically organized from top to bottom as (1) the hair canal, which becomes indistinct after birth, (2) infundibulum that extends to the opening of the sebaceous (oil) gland duct, (3) sebaceous gland that produces the oil that keeps hair lubricated, (4) the isthmus that begins at the sebaceous gland and ends at (5) the bulge, where the arrector pili muscle inserts [the little muscle that makes hair stand on end in response to cold or fear] and where follicular epithelial stem cells are located [stem cells that may be capable of generating new matrix cells and initiating new follicles], (6) the keratinization zone where the hair shaft acquires its tough coating of keratinocytes, and (7) the hair bulb that contains the hair matrix where a new hair is generated, and melanocytes that contribute to hair color.
Biological Activity of the Hair Follicle
The hair follicle has constant biological interaction with the rest of the body. It exchanges biological signals with the body by cell-to-cell contact, and via the follicle’s rich blood and nerve supply. Biological signaling tells the follicle when to cycle that is, when to produce a new hair, shed a degraded hair, and when to rest.
Under instructions from genes that carry follicle-forming and hair-forming information from one’s ancestors, the hair follicle produces hair that reveals one’s ancestral characteristics in diameter (fine to heavy), cross-section (round or oval), stiffness (flaccid to brushlike), and color (blond, red, brunette or black).
The entire process of follicle activity and hair production is dependent, in some degree, on hormonal controls-chiefly the androgenic “male” hormone testosterone, but also on thyroid hormone and “female” hormones in women. Hair follicles on the face, torso, arms and legs and scalp are androgen-dependent for growth and development. Follicles at the top, front and sides of the scalp can cease to function in response to a particular form of testosterone; this is the condition called androgenetic alopecia or familial hair loss.
Cycling of Hair Growth
Normal hair cycling is associated with the temporary loss of hair and the growth of new hair from the same follicles. The hair growth cycle in humans occurs in three phases:
- Anagen-growth phase
- Catagen-degradation phase
- Telogen-resting phase
There is no break or discontinuity between phases; the hair cycle is a continuous process that occurs for the life of the hair follicle. A complete scalp hair cycle stretches over 2 to 8 years:
- Anagen (growth)-2 to 8 years
- Catagen (degradation)-2 to 4 weeks
- Telogen (rest)-2 to 4 months
The “dead” hair that was degraded during the catagen (degradation) phase is pushed out of the follicle when a new hair emerges in anagen (growth) phase. A healthy person with a full head of hair will shed on average 50 to 100 “dead” hairs per day. Shedding can be influenced by internal factors such as age, change in hormonal or nutritional status, skin disease and stress, and by external factors such as cancer chemotherapy, ionizing radiation, and exposure to some types of industrial chemicals.
All follicles, everywhere on the body, undergo hair cycling. The duration of each cycle may vary by body site; on the same person, scalp hair cycling may be slightly different in duration from body hair cycling.
Hormonal Controls of Hair Growth
Androgenic (male) hormones are essential for the growth of human hair everywhere on the body to a variable extent. In boys, especially, the appearance of body and facial hair occurs in parallel with increase in levels of androgenic hormones as the body matures sexually. The relative absence of heavy hair growth on the bodies and faces of girls is an external indication of the relatively lower levels of androgenic hormones in girls.
Although androgens are necessary to the development of body and facial hair, they are not sufficient in and of themselves. The complex, genetically driven biochemistry of human development also brings thyroid hormones and “female” hormones into play in stimulation of hair follicles.
Unlike hair follicles on the face and body, scalp hair follicles are not androgen-dependent for growth and development. However, the androgenic hormone testosterone has a paradoxical role in permanent scalp hair loss-the condition known as androgenetic alopecia. (see Hair Loss and Its Causes).
Androgenetic alopecia-also called male-pattern hair loss and female-pattern hair loss-has a genetic basis and is often described as “running in the family”. In persons who carry the gene or genes involved in androgenetic alopecia, an enzyme (Type II 5-alpha reductase) in scalp hair follicles metabolizes testosterone to an isoform called 5-alpha-dihydrotestosterone. The presence of this isoform of testosterone in the follicles influences the follicles to cease normal hair cycling. If these follicles henceforth produce hair at all, it will be miniaturized “peach fuzz” hair.
The same enzyme, 5-alpha reductase, acting on testosterone is associated with prostate gland enlargement (benign prostatic enlargement or BPH ) in men. The hair restoration drug finasteride (Propecia®) neutralizes 5-alpha reductase and thus is successful in slowing or halting hair loss, on in stimulating new hair growth, in some men. A more potent form of finasteride (PROSCAR®) is used to treat BPH in some men. (see Hair Loss Treatments).
Types of Hair
Under genetic control, hair follicles are formed and develop to produce different kinds of hair for different purposes. Hair can be body-site specific: nostril hair, eyelashes, eyebrows, hair in the genital area, torso hair and scalp hair have different physical qualities specific to their function. The physical characteristics of hair may change over time or under the influence of hormonal changes in the body.
Genetic ancestry influences the physical qualities of hair-heavy, fine, straight, curly, color. For example, Asian ancestry is associated with black, large-diameter, straight hair; African ancestry is associated with black, tightly curled hair; Scandinavian ancestry is associated with red or blond hair of fine texture. The number of genes and the specific genes involved in determination of hair qualities is not known with certainty.
Hair as a Biologic Fiber
Hair is not “alive” like other body tissues. Hair is a non-living fiber made up of biological components. The components are assembled into a hair in the hair follicle. The beginning of the biological production line that produces a hair is in the matrix cells at the base of the follicle.
The major components of a hair shaft are the cortex and the cuticle:
- The cortex constitutes the bulk of the hair fiber. It is made up largely of keratins, a family of proteins that also provide the tough outer sheath of skin cells.
- The cuticle is the armor of the hair shaft. Made up of thin scales of dense keratin, it protects the cortex from physical and chemical damage. Seen under a microscope, the layered scales of cuticle resemble the armored scales of a reptile. When the cuticle is damaged by chemicals or physical trauma, the cortex is exposed and open to damage. A typical appearance of such damage is broken hair and “split ends“.
The color of hair is determined by follicular melanocytes (cells containing the coloring pigment melanin). The melanocytes are located in the matrix area of the follicle. Interestingly, melanocytes are “switched on” only during the anagen (growth) phase of the follicle; they are “switched off” during catagen and telogen phases. The melanocytes usually produce only one type of melanin pigment at a time, but two types can be produced. The pigment type eumelanin is the principal coloring agent in brown and black hair. The pigment type pheomelanin is the principal coloring agent in blond and red hair. Absence of pigment produces white hair, and diminished pigment produces gray hair.
While the general principles of hair coloration are understood, it is still not known how subtle variations of hair color are produced. The subtle shading of hair depends not only on pigmentation but also on how sunlight and artificial light is reflected and refracted by interfaces of cuticle scales.
The Hair Follicle in Wound Repair
Production of hair is the primary function of hair follicles. Recent scientific investigations have shown that stem cells located in the “bulge” area of the follicle can be involved in wound repair and long-term maintenance of a healthy skin.
Hair Science on the Cutting Edge
Hair follicle at the level of gene, gene product and cells is not yet ready for application in hair restoration. When such application may be possible cannot yet be predicted, but most investigators agree that there will be clinical applications.
Meanwhile, basic centering on the hair follicle is producing interesting insights into human and mammalian biology.
Hair follicle development is known to be under genetic control. has shown that hair follicle development begins and ends before a human is born. The first identifiable hair follicles appear in the embryo at about 9 weeks; their development from stem cells into specialized cells that will form hair follicles is dictated by molecular signals orchestrated by genetic instructions. The development of hair follicles follows a pattern: the first hair follicles appear on the embryo where there eventually will be an upper lip and chin. Hair follicle development on body, face and scalp begins at fetal age of 4 to 5 months. The fully formed 9-month fetus has all of the hair follicles that will ever develop on that person. After birth, no additional hair follicles will ever develop.
that could eventually lead to the ability to reprogram inactive hair follicles, or even to create new hair follicles, follows several courses:
- Genetic approaches to identify hair follicle genes
- Cellular approaches and stem cell reprogramming
- Combined stem cell and genetic approaches to hair follicle induction
Genetically stable strains of laboratory mice are used as models of human hair loss. Genes such as the one named hairless that occurs in both mice and humans have well-documented inheritance patterns and well-documented mutations that produce distinct types of hair loss. In humans, some genes associated with hair loss are also associated with physical deformities or intellectual impairment. Some human hair loss conditions, such as alopecia areata, are thought to result from a complex combination of genetic and environmental factors. (see Hair Loss and Its Causes for more information about alopecia areata) Studies are underway to identify the gene or genes associated with alopecia areata.
Intense investigation has focused on the finding that multi-potent stem cells are present in the “bulge” area of the hair follicle. The finding suggests that hair follicles could possibly be a source of easily obtainable adult stem cells adaptable to cell-based therapies. Follicular stem cells may be involved in repair of wounds at the skin surface.