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Contents lists available at ScienceDirect

Maturitas
journal homepage: www.elsevier.com/locate/maturitas

Review

Age-related hair changes in men: Mechanisms and management

of alopecia and graying
Paradi Mirmirani a,b,c,∗
a
Department of Dermatology, The Permanente Medical Group, Vallejo, CA, United States
b
Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States
c
Department of Dermatology, Case Western Reserve University, Cleveland, OH, United States

a r t i c l e i n f o a b s t r a c t

Article history: The appearance of human scalp hair is often tied to perceptions of youth and virility, especially in men.
Received 16 October 2014 Hair loss, or alopecia and hair graying are commonly associated with advancing age and are frequently
Accepted 17 October 2014 a source for emotional distress and anxiety. Our understanding of the complex molecular signals and
Available online xxx
mechanisms that regulate and influence the hair follicle has expanded in recent years. By harnessing
this understanding we are poised to address the esthetic concerns of aging hair. Additionally, changes
Keywords:
in the hair follicle may be a reflection of systemic senescent signals, thus because of its accessibility,
Alopecia
the hair follicle may serve as an important research tool in gerontology. In this review, the most current
Hair loss
Senescent alopecia
knowledge and research regarding mechanisms of androgenetic alopecia, senescent alopecia, and graying
Androgenetic alopecia are discussed, as are extrinsic factors that may contribute to hair changes with age. Evidence based
Male pattern balding management strategies for treatment of age-related hair changes are also reviewed.
Graying © 2014 Elsevier Ireland Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2. Androgen mediated hair loss: androgenetic alopecia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3. Non-androgen mediated hair loss: senescent alopecia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4. Extrinsic factors (chemicals, heat, ultraviolet light, smoking) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5. Hair graying . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
6. Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
6.1. Androgenetic alopecia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
6.2. Senescent alopecia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
6.3. Hair shaft . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
6.4. Hair graying . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Competing interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

∗ Corresponding author at: Department of Dermatology, The Permanente Medical Group, 975 Sereno Drive, 2nd Floor, Hallway F, Vallejo, CA 94589, United States.
Tel.: +1 011 1 707 651 5143; fax: +1 011 1 707 651 2667.
E-mail address: paradi.mirmirani@kp.org

http://dx.doi.org/10.1016/j.maturitas.2014.10.008
0378-5122/© 2014 Elsevier Ireland Ltd. All rights reserved.

Please cite this article in press as: Mirmirani P. Age-related hair changes in men: Mechanisms and management of alopecia and graying.
Maturitas (2014), http://dx.doi.org/10.1016/j.maturitas.2014.10.008
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1. Introduction
The hair follicle is a unique structure in that it undergoes con-
tinuous cycles of growth (anagen), resorption (catagen), and rest
(telogen) from birth until death. During anagen, each individual
hair follicle produces a new hair shaft. The size, length and pig-
ment of the hair shaft vary depending on the location on the body
and can change under the influence of biologic signals. The rea-
son for the relative abundance of scalp hair compared to body hair
in humans is not completely understood. Perhaps because of this
prominence, the appearance of human scalp hair is often tied to
perceptions of youth and virility, especially in men. Thus alopecia
and graying, which are almost universal with advancing age, are
often a source of anxiety and distress.
Follicular stem cells are responsible for regeneration of the hair
follicle with each new cycle and recapitulate many of the signals
of embryologic development. Various factors are known to influ-
ence and alter the regenerating hair follicle with advancing age.
Androgens are the most extensively studied modulator of the hair
follicle. However non-androgen senescent signals as well as extrin-
sic factors such as ultraviolet light and smoking are also likely to
influence the function and fidelity of the hair follicle. Hair graying
occurs as a result of alterations to the melanocytes, or specialized
pigment-producing cells, that are associated with each hair follicle.
Newer studies have shed light on the critical role of reactive oxygen
species that lead to loss of melanocytes and pigment production.
2. Androgen mediated hair loss: androgenetic alopecia
Androgenetic alopecia (androgenetic alopecia), also known as
male pattern hair thinning or male pattern balding is the most well
recognized cause of hair thinning. Although there is no clear demo-
graphic data, it is often stated that up to 50% of men will manifest
some degree of androgenetic alopecia by age 50 [1]. There is sig-
nificant variation among the races with the greatest penetrance
in Caucasians and the least among Africans [2]. Although exten-
sive genetic studies have not been done, a polygenetic inheritance
of baldness is suspected given the high prevalence of the trait, the
strong concordance between family members, and the fact that risk
increases with the number of relatives already affected and the fact
that risk increases with the number of relatives already affected
[3–7].
In men with androgenetic alopecia, large caliber hairs become
progressively finer and thinner (miniaturized) leading to decreased
coverage of the scalp; in some cases the hairs become so fine that
they are barely visible to the eye. In those who are genetically
susceptible, hair miniaturization can begin as early as the teens,
twenties and thirties [8]. Interestingly, these changes occur only in
certain regions of the scalp, specifically the frontal hairline, the top
of the scalp and the crown or vertex scalp; the follicles along the
sides and back of the scalp are spared even in men with extensive
balding. These regional variations in patterns of scalp hair thinning
may reflect differences in embryologic scalp patterning [9], lev-
els of hormonal receptors [10] or other factors that may influence
follicular growth [11].
Pathophysiologically, androgens mediate and drive the follicu-
lar transformation in androgenetic alopecia. There is a substantial
increase in the local, or follicular, transformation of testosterone
to dihydrotestosterone by the enzyme 5␣-reductase [12]. Dihy-
drotestosterone, which has a five times higher affinity for the
androgen receptor compared to testosterone, triggers specific
genes that then lead to the gradual miniaturization of genetically
programmed hair follicles [13].
The effects of androgens on the follicle have, for the most part,
been studied in men under the age of 50. It is suspected that to
some extent, hair loss in later years is mediated by both andro-
gen as well as non-androgen signals. This idea is supported by the
observation that there is a progressive decline in testosterone lev-
els with advancing age with some reports suggesting that up to
25% of men over age 70 meet laboratory criteria for hypogonadism
[14–16]. Additionally, tissue activity of 5␣-reductase in the scalp
decreases with age. This pervasive waning of circulating andro-
gens and androgen activity suggests that non-androgen-related
hair thinning may be an important factor in age-related hair thin-
ning.
3. Non-androgen mediated hair loss: senescent alopecia
Various reports have suggested that decreased hair density and
diameter occur with advancing age [17–21]. Such hair thinning
is often identified as a marker of systemic senescence in humans
and other mammals. In support of this concept, it is observed that
patients with progeria, who have genetically programmed prema-
ture senescence, show a phenotype of hair loss [22].
The following criteria have been proposed for making the diag-
nosis of senescent alopecia: (1) hair thinning that does not become
apparent until after approximately 50 years of age and (2) no fam-
ily history of androgenetic alopecia [19,23,24]. Alternate terms that
have been used include “late onset” or “age-related” hair thin-
ning. In reality, senescent alopecia likely coexists with androgenetic
alopecia in many patients. Clinically, the hair thinning in senescent
alopecia is often described as being diffuse when seen in its “pure
form” but having both a diffuse and patterned thinning when seen
in combination with androgenetic alopecia [24,25]. Histologically,
there is follicular downsizing or miniaturization of the follicle in
both androgenetic alopecia and senescent alopecia [26].
Although androgenetic alopecia and senescent alopecia share
many clinical and histologic features, the mechanisms by which
follicular downsizing and miniaturization occur has recently been
shown to be distinct [27]. Microarray comparison of age-matched
subjects with androgenetic alopecia, senescent alopecia and nor-
mal controls without hair loss has shown that androgenetic
alopecia is associated with altered expression of genes known to
be required for hair follicle cycling. In stark contrast, the transcrip-
tional profile of senescent alopecia reveals changes in the complex
phenomenon of alternative splicing, oxidative stress response, and
apoptosis, which are characteristic of aging tissues [27]. This dif-
ference in mechanism has significant implications in terms of
treatment of hair loss at different ages. Further characterization of
these senescent pathways may lead to attractive therapeutic tar-
gets for treatment of senescent alopecia, but may also prove to be
useful markers of other systemic senescent processes.
4. Extrinsic factors (chemicals, heat, ultraviolet light,
smoking)
The hair is made primarily of keratin bundles that are compacted
together and surrounded with an outer cuticular layer to form
a rope-like structure that is flexible yet strong. Sulfur crosslinks
within the keratin provide for the strength of the hair. The outer
cuticle resembles overlapping shingles on a roof and forms the
“armor” that protects the underlying hair shaft. The quality and
caliber of the hair shaft, or hair fiber decreases with age and can
significantly affect how the hair is perceived [28]. Additionally,
the aged hair fiber is more susceptible to damage and breakage
from a variety of external insults, the general term for which is
“weathering.”
Although extensive hair styling is not as common in men as in
women, various hair care techniques may not be well tolerated
with advancing age. Heat, coloring agents, and chemicals used for

Please cite this article in press as: Mirmirani P. Age-related hair changes in men: Mechanisms and management of alopecia and graying.
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permanent waves/straightening can lead to weakened, weathered
hair that has decreased tensile strength and decreased manageabil-
ity leading to “flyaway hairs”, hair tangling, rough hair, or breakage
[29].
Ultraviolet light can lead to oxidative changes of the hair shaft
resulting in damage to both the hair color (photobleaching) as well
as weathering of the hair structure [30]. With age and graying,
the absence of the natural protective pigments in the hair leads
to increased ultraviolet damage [28].
Observational studies have shown an association between
smoking and premature graying and baldness in men [31,32]. Dis-
cordance of hair loss in a monozygotic twin pair has lead further
support to the speculation that smoking negatively affects the hair
[33]. Although the mechanism by which smoking impacts the hair
has not been well studied, it is likely that deficits in microcirculation
and increased oxidative damage may be contributory.
5. Hair graying
Hair graying is one of the most notable changes of aging. It is
often quoted that as a rule of thumb, 50% of people are 50% gray
by the age of 50 [28]. Recent epidemiologic studies of men and
women of various races suggests a far lower number-only 6–23% of
people have 50% gray hair at age 50 [34]. People of Asian and African
descent showed less gray hair than those of Caucasian origin [34].
The age of onset of hair graying is also influenced by genetics.
Much like the skin, the pigment of the hair shaft is derived from
specialized cells termed melanocytes, which transfer pigment, or
melanin, via organelles called melanosomes. However, unlike the
skin in which there is continual production of pigment, the activity
of the melanocytes surrounding the hair follicle is intermittent and
is tightly linked to follicular cycling. Hair pigmentation occurs only
during the growth, or anagen, phase which typically lasts 3–5 years.
With each hair cycle, various factors may impact the fidelity of hair
pigmentation. Studies have shown that gray hair is associated with
a decrease in follicular melanocyte population and a decrease in
melanin content [35]. A buildup of reactive oxygen species along
with a decreased ability to handle oxidative damage has also been
implicated in the process of graying [36–38].
6. Management
6.1. Androgenetic alopecia
Treatment of men with androgenetic alopecia includes medi-
cal, surgical, low-level laser light and cosmetic options. Currently
there are two medications approved by the US Food and Drug
Administration for hair regrowth and reversal of miniaturization
in androgenetic alopecia: topical minoxidil and oral finasteride
[39,40]. Both of these treatments have been extensively studied,
and the level of evidence for their efficacy is strong [41]. The mech-
anism of action of topical minoxidil on hair regrowth is not fully
understood [42]. Minoxidil is a potent vasodilator that acts through
nitric oxide pathways and as a potassium channel opener [43], but
its hair re-growth properties appear to be independent of its vasodi-
lation properties. Although the clinical trials of topical minoxidil in
men with androgenetic alopecia have evaluated only hair growth
properties of the vertex scalp [44,45], studies suggest that the med-
ication is effective in other scalp regions in which there is also hair
miniaturization [11]. In clinical trials, 5% topical minoxidil solution
used regularly can partially re-enlarged the miniaturized hairs and
prolong the anagen phase [46,47]. Minoxidil is also available as a
5% foam [45].
Oral finasteride, an inhibitor of type 2 5␣-reductase, taken in
a 1 mg dose has shown to slow hair loss, increased hair growth,
Please cite this article in press as: Mirmirani P. Age-related hair changes in men: Mechanisms and management of alopecia and graying.
Maturitas (2014), http://dx.doi.org/10.1016/j.maturitas.2014.10.008
3
and improve the appearance of hair as compared to placebo [48].
Approximately thirty percent hair improvement is seen with long-
term use; endpoints included hair counts along with patient and
investigator assessments of global photographs [48,49]. Benefits
are seen in both the frontal and vertex scalp, although the improve-
ments are greater at the vertex scalp and are typically seen after
6 months of use. Finasteride is generally well tolerated and has
no drug-drug interactions [48]. In studies, 2% of patients reported
sexual side effects that resolved with discontinuation of the drug
[48]. Levels of prostate-specific antigen can be decreased with
finasteride therapy, thus measurement of baseline prostate specific
antigen is recommended prior to starting the medication [48]. Post
marketing reports of increased rates of high-grade prostate cancer
and persistent sexual side effects have been controversial and are
still being evaluated [50–52].
Surgical hair restoration involves harvesting donor hair follicles
from the occiput and surgically transferring these follicles to the
affected frontal scalp. Results are permanent because the donor
hair from the occiput is androgen independent and maintains its
growth characteristics. Transplantation of follicular units in small
bundles of 1–4 hairs allows for an esthetically natural look, but the
cost of treatment as well as the supply of adequate donor hair may
be a limiting factor.
Devices that emit low-level visible or near infrared light laser
light have been shown to improve terminal hair counts in men
with androgenetic alopecia [53,54]. The mechanism of hair growth
promotion is not fully understood.
Use of cosmetic devices and camouflage techniques such as
powders or creams can provide temporary scalp coverage; hair-
pieces are another option commonly employed. These techniques
will not affect the underlying hair thinning process.
The above treatments can be combined to provide a synergistic
effect in hair regrowth and cosmetic appeal.
6.2. Senescent alopecia
The mechanisms that lead to hair thinning and miniaturization
after the age of 60 are distinct from the androgen-mediated signals
that trigger miniaturization in androgenetic alopecia. Androgens
wane with age as does the level of 5␣-reductase which converts
testosterone to dihydrotestosterone in the hair follicle. Thus, use of
finasteride, a specific blocker of 5␣-reductase is unlikely to lead to
significant hair regrowth in men who have hair thinning after the
age of 60. Clinical observation of older men who take finasteride
at a 5 mg dose for prostate hypertrophy show no significant hair
regrowth.
Other than finasteride, all of the other treatment modalities dis-
cussed above for androgenetic alopecia can be employed in men
with senescent or age-related thinning.
In the future, as the signals involved in senescent hair thinning
are better characterized, targeted treatment may be available.
6.3. Hair shaft
Treatment of damaged or broken hair includes avoidance of any
heat, chemicals, or tension, cutting off the damaged hair, gentle
care (minimizing friction to the hair) and regular use of a hair
conditioner. There is also good evidence that protection from ultra-
violet light will help maintain the integrity of the hair and decrease
weathering.
There are no clear-cut guidelines for safe use of chemicals or
heat since different hair types will have a highly variable tolerance
for processing [55–57]. However, in general, with age, the hair shaft
becomes less tolerant of chemicals, heat, and friction so that hair
practices that were previously done without trouble should be done
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less frequently or with great caution as sub-clinical damage may
lead to visible hair changes.
6.4. Hair graying
Other than cessation of smoking, there is currently no thera-
peutic intervention for preserving hair color or preventing graying.
Hair dyes or colorants are currently the mainstay for changing gray
hair color. Identification of the molecular mechanisms of graying
may pave a path for targeted treatment in the future.
7. Conclusions
Androgenetic alopecia and senescent alopecia represent two
mechanisms by which hair miniaturization and thinning occur in
men. In androgenetic alopecia, hormonal signals lead to changes in
genes regulating hair follicle size and cycling and there is a grad-
ual diminution of the hair follicle. In senescent alopecia, which
has its onset after the age of 60, follicular dropout and thinning
occur as a results of apoptosis and oxidative stress responses and
may be a manifestation of systemic aging processes [27]. Extrin-
sic factors such as hair processing, ultraviolet light, and smoking
also have a negative effect on the hair. Hair graying may reflect a
decreased ability to handle oxidative damage as well as loss of fol-
licular melanocytes and melanin content [35]. Current treatments
include medical, surgical, light based, and cosmetic treatments. In
the future, targeted treatments will likely be available.
Contributors
This review manuscript is the sole work of Paradi Mirmirani.
There were no other contributors.
Competing interest
None.
Funding
Dr. Mirmirani has received research funding from the Johnson
and Johnson and the Procter and Gamble companies.
Provenance and peer review
Commissioned; externally peer reviewed.
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Please cite this article in press as: Mirmirani P. Age-related hair changes in men: Mechanisms and management of alopecia and graying.
Maturitas (2014), http://dx.doi.org/10.1016/j.maturitas.2014.10.008