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Structural Characteristics of the Aging Skin: A Review
Miranda A. Farage a; Kenneth W. Miller a; Peter Elsner b; Howard I. Maibach c
a
The Procter & Gamble Company, Winton Hill Business Center, Cincinnati, Ohio,
USA
b
Klinik Fur Dermatologic, Jena, Germany
c
Department of Dermatology, University of California, San Francisco, California,
USA

Online Publication Date: 01 October 2007

To cite this Article: Farage, Miranda A., Miller, Kenneth W., Elsner, Peter and
Maibach, Howard I. (2007) 'Structural Characteristics of the Aging Skin: A Review',
Cutaneous and Ocular Toxicology, 26:4, 343 - 357
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 Cutaneous and Ocular Toxicology, 26: 343–357, 2007
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DOI: 10.1080/15569520701622951

STRUCTURAL CHARACTERISTICS OF THE AGING

SKIN: A REVIEW

Miranda A. Farage and Kenneth W. Miller

The Procter & Gamble Company, Winton Hill Business Center, Cincinnati,
Ohio, USA

Peter Elsner
Klinik Fur Dermatologic, Jena, Germany

Howard I. Maibach
University of California, Department of Dermatology, San Francisco,
California, USA

As life expectancy in industrialized countries increases, appropriate care of elderly skin

looms as a dermatologic priority. Skin aging is a complex, multifactorial process whose
baseline rate is genetically determined but that may be accelerated by environmental, mech-
anical, or socioeconomic factors. The intrinsic structural changes that occur with the aging
of the skin increase skin fragility, decrease the ability of the skin to heal, increase risk for
toxicological injuries, promote the development of various cutaneous disorders, and produce
aesthetically undesirable effects like wrinkling and uneven pigmentation. As aged patients
represent a larger segment of the population, increased attention to the problems of the aged
skin, both cosmetic and beyond, will be necessary and should build on currently successful
interventions to improve their quality of life.

Keywords: Aging population; Aging skin; Barrier function; Collagen; Dermis; Elastin; Skin thickness

INTRODUCTION
In 1900, life expectancy in the United States was just 50 years, with only 4% of
the American population over the age of 65 (1). By the year 2000 (largely due to
better diet and medical care) (2) that percentage had tripled, with life expectancy
currently averaging 77.6 years overall (2) (Figure 1). It is predicted that life expect-
ancy in the U.S. and other industrialized countries will continue to increase, hitting
100 years by about 2025 (3). Women, with longer average life expectancies than men,
can expect to spend more than one-third of their lifetimes in menopause (4). As the
aged population continues to increase in numbers, the various implications of
cutaneous aging will increase in medical importance.

Address correspondence to M. A. Farage, Ph.D., The Procter and Gamble Company, Winton Hill
Business Center, 6110 Center Hill Road, Box 136, Cincinnati, OH 45224, USA. Tel.: +1 513 634 5594;
Fax: +1 513 634 7364; E-mail: farage.m@pg.com

343
 344 M. A. FARAGE ET AL.
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Figure 1 Mean life expectancy in the United States by year from the National Vital Statistics Report
(NVSS) from the Centers for Disease Control, U.S. Department of Health and Human Services. November
10, 2004.

Aging is a complex, multifactorial phenomenon involving both intrinsic and

extrinsic parallel processes that contribute progressively to a loss of structural integrity
and physiological function of the skin that leads, inevitably, to death. Aging proceeds
at intrinsically different rates, driven by genetic regulation, the toxicity of certain by-
products of metabolism and a lack of sufficient physiological resources dedicated to
somatic maintenance and repair (5). Factors contributing to aging can be divided into
four main categories: biological (genetically determined and inalterable), environmen-
tal (damage associated with exposure to sunlight, pollution or nicotine), mechanical
aging (repetitive muscle movements such as squinting or frowning), and miscellaneous
factors including diet, sleep patterns, morbidity, and mental health (5).
Although skin is incredibly durable, it is affected, like all other organ systems,
by aging (6). The synergistic effects of intrinsic and extrinsic aging factors over the
human lifespan combine to cause deterioration of the cutaneous barrier and
the structural integrity of the skin (7). Hormonal changes that also play a role in
the aging of skin, especially in females, lead to earlier signs of aging for women (8).
Most skin aging therapies aim at reversing aesthetically unwelcome signs. However,
skin aging can also produce significant morbidity, pervasive dryness and itching (9) and
increased risk of numerous skin diseases, including cutaneous malignancy (9). In fact,
most people over 65 have at least one skin disorder, and many have two or more (10).
Defining the retractable aspects of cutaneous aging (primarily hormonal and
lifestyle influences) from the irretractable (primarily intrinsic aging) is essential to
the understanding of the aging skin. As the population ages, the dermatologic focus
 STRUCTURAL CHANGES OF AGING SKIN 345

must shift from cosmetic interventions to improving morbidity and quality of life for
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this growing segment of the population (11). The structural changes of the aging skin
will be discussed in this article, whereas the physiological changes and lifestyle influ-
ences on the skin will be reviewed separately.

STRUCTURE AND FUNCTION OF NORMAL SKIN

The human integument, one-sixth of the total body weight (12), forms the most
visible indicator of age. A sophisticated and dynamic organ, serving as a barrier
between the internal environment and the world outside, yet has numerous functions
that go far beyond that role (13) including: homeostatic regulation, prevention of
percutaneous loss of fluid, electrolytes, and proteins; temperature maintenance; sen-
sory perception; and immune surveillance (12).
The skin is commonly subdivided into three layers: epidermis, dermis, and
hypodermis (Figure 2).

Epidermis
The epidermis (the external skin surface), although widely variable, typically
measures 50 mm to 100 mmin thickness (14). This layer contains primarily keratino-
cytes, with smaller populations of Langerhans cells and melanocytes (Figure 2)
(11). Although slight variation is reported in the literature, the keratinocyte popu-
lation in the epidermis is completely replaced approximately every 30 days (15).
The epidermis is a dynamic system whose metabolic activity is largely regulated
by the integrity of the permeability barrier (11), which is responsible for maintaining
the fine balance between clinically normal and dry skin (8). This function resides in

Figure 2 Normal skin structure showing layers of dermis and epidermis.

 346 M. A. FARAGE ET AL.

the outermost layer of the epidermis, the stratum corneum (16). The stratum corneum
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is a dynamic, metabolically interactive tissue (16) comprised of about 60% structural

proteins, 20% water, and 20% lipids (11,17). Its integrity depends on its lipid compo-
sition,16 primarily cholesterol, ceramides, and free fatty acids (11,16).
The dynamic nature of the stratum corneum makes it vulnerable to derange-
ment of barrier function (11). Skin is considered clinically dry when the moisture
content falls below 10%, at which point the stratum corneum becomes less flexible
and begins to crack or fissure (8). Dehydration can result in a reduced capacity to
inhibit entry of pathogenic microbes (11).

Dermis
The dermis, 2 to 3 mm in thickness, is a layer composed predominantly of con-
nective tissue and blood vessels, that comprises the main bulk of the skin (4) (Figure 2),
supports the epidermis, and binds it to the hypodermis (12). Dermal connective tissue
contains elastin and collagen; collagen fibers comprise the biggest volume of the skin
and the bulk of its tensile strength (4), whereas elastin fibers contribute to elasticity
and resilience (4). The dermis also contains nerve fibers, sensory receptors, hyaluronic
acid (responsible for normal turgor of dermis because of extraordinary water-holding
capacity), and supportive glycosaminoglycans (GAG) (4).

Hypodermis
Below the dermis is the hypodermis, a layer of loose connective tissue that
binds the skin to internal organs. This layer contains subcutaneous fat as well as are-
olar tissue, providing cushioning, thermoregulation, and skin stability by connecting
dermis to internal organs (18).

STRUCTURAL CHANGES IN AGED SKIN

As the skin ages, changes are seen in skin thickness and quality of the epidermis
and dermis as discussed later (Figure 3 and Table 1).
Recent technical progress has allowed more objective and precise characteriza-
tion of the aging human skin (19). Great progress has been made in noninvasive, in
vivo imaging of the skin (20), and improved bioengineering methods allow more
accurate analysis of its mechanical properties.
Ultrasound echogenicity studies yield images that provide information on
changes in ultrastructural features of skin (19). Laser Doppler Velocimetery
(LDV) analyzes cutaneous blood perfusion (19). LDV penetrating as deep as
1 mm yields data on deeper vessels not visible by capillaroscopy methods. Two
new microscopy procedures allow direct measurement on unmodified skin. Confocal
laser scanning microscopy (CLSM) (18–20) does not penetrate the skin, but can
visualize individual cells, measuring images parallel to skin surface (18,20). Although
optical coherence tomography (OCT) (18,20) enables imaging of skin as deep as
2 mm, it cannot resolve individual cells (18,20). Pulsed ultrasound, which can be used
on any site, is useful for determination of whole skin thickness (19).
 STRUCTURAL CHANGES OF AGING SKIN 347
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Figure 3 Differences in skin structure between normal and aged skin.

Skin Thickness Changes

The skin, which thickens over the first 20 years, thins progressively over adult
life at a rate that accelerates with age (19), even though the number of cell layers
remains stable (21).The epidermis decreases in thickness (9) with age; this change
is most pronounced in exposed areas, including the face, neck, upper part of the
chest, and the extensor surface of the hands and forearms (22). Epidermal thickness

Table 1 Changes in the structure of aged skin

Skin structure Observed effect of aging Reference

Stratum corneum Lipid content decreased Saint Leger et al. (53)

Epidermis Flattening of dermal-epidermal junction Neerken et al. (20)
Number of enzymatically active melanocytes Rees (14)
decreases by 8% to 20% per decade
Number of Langerhan’s cells decreases Fenske & Lober (6)
Capacity for re-epitheliazation diminishes Orenteich & Selmanowitz (54)
Dermis Decrease in thickness (atrophy) Waller & Maibach (19)
Vascularity decreases as does cellularity Duncan & Leffell (31)
Decrease in collagen synthesis Phillips & Kanj (26)
Pacinian and Meissner’s corpuscles degenerate Phillips & Kanj (26)
Structure of sweat glands becomes distorted, Phillips & Kanj (26)
numbers of functional sweat glands decreases
Elastic fibers degrade McCallion & Li (8)
Decrease in number of blood vessels Duncan & Leffell (31)
Hypodermis Change in distribution of subcutaneous fat Phillips & Kanj (26)
Appendages Hair loses normal pigments Phillips & Kanj (26)
Hair thins Phillips & Kanj (26)
Decrease in sweat glands Phillips & Kanj (26)
Abnormal nail plates Phillips & Kanj (26)
 348 M. A. FARAGE ET AL.

decreases about 6.4% per decade (19,23), and decreases even faster in females.
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Dermal thickness also decreases, but at the same rate in both genders (8).

Epidermal Changes
Cell numbers in the epidermis are reduced in older adults (24). Keratinocytes,
as skin ages, change shape, becoming shorter and fatter (24) whereas corneocytes in
aged skin become bigger as a result of decreased epidermal turnover (21,25). Epider-
mal turnover time is increased in aged skin (6,18).
Enzymatically active melanocytes decrease at a rate of 8% to 20% per decade,
resulting in uneven pigmentation in elderly skin (26). A parallel decrease in the num-
ber of Langerhan’s cells leads to impairment of cutaneous immunity (26). An atypia
in cells of the basal layer is also observed (19) Although the number of sweat glands
does not change, sebum production decreases (26) whereas a reduction of the natural
water and fat emulsion on the skin is observed (27). Water content in aged dry skin,
particularly in the stratum corneum, is lower than that of younger skin (8,9,11).
Aging skin dries, with a greater tendency to xerosis (9). Changes in the amino acid
composition in aged skin (8) also reduce the amount of cutaneous natural moisturiz-
ing factor (NMF), thereby decreasing its water binding ability (11).

Barrier Function
Because permeability barrier function in aging epidermis does not appear to be
impaired under basal conditions, it has been generally assumed that barrier function
does not alter significantly with aging (28). Baseline transepidermal water loss
(TEWL), however, decreases with age (9,28) an observation believed to be due to
the reduction of the water content of aged skin. In other words, the elderly lose less
because they have less water to lose. The authors of this study did not, however,
adjust results for mass (28). Recovery of baseline TEWL values after occlusion is
slower in older skin (9).
Further studies revealed that aged skin was much more easily disrupted by
tape-stripping than was younger skin (28), requiring only 18 strippings in individuals
over 80 years of age as compared to 31 strippings in young and middle-aged adults.
Recovery of barrier function in the aged subjects was also dramatically different.
Only 15% of those older than 80 had recovered barrier function at 24 h, compared
to 50% of the younger group (28). Artificially induced water gradients (such as pro-
duced by occlusion) were shown to dissipate more slowly in older skin than in
younger (11), with occluded older skin having a significantly higher TEWL than
younger skin as well (11). Depending on the compound and the anatomic site eval-
uated, significant differences in barrier permeability have been observed (23).
The findings reveal a profound change in barrier integrity even though barrier
function under normal conditions appears normal. Baseline TEWL measurements
then, because they do not reflect actual functional status, can be misleading (28).
A lack of functional reserve is exposed when the epidermal permeability barrier is
under stress (28). Interestingly, one study found that with the drying skin character-
istic of intrinsic aging, TEWL and the water content of the stratum corneum drop in
 STRUCTURAL CHANGES OF AGING SKIN 349

parallel, while in pathological conditions, TEWL increases even though stratum

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corneum water content stays low. In stripped skin, both values increase (29).

Lipid Composition
Although the lipid composition of the aged skin is not significantly altered, the
global lipid content of the aged skin is reduced (14,28). Total lipid content in aged
skin decreased as much as 65% (24). An age-related decrease in the amount of lipid
in the stratum corneum was also observed as well (9). An age-related decrease in the
sterol ester and triglyceride fraction of stratum corneum lipids was also observed (9).
Also, histological studies reveal that the number of papillae per area decreases dra-
matically (27), from an average of 40 in young skin, down to 14 papillae=mm2 in
those aged over 65 (30).

Dermal–Epidermal Junction
The most reproducible structural change in aged skin is a flattening of the
dermal–epidermal junction occurring as a result of rarification and reduction of
dermal papillae (30).This flattening, seen in scanning electron images at about the
sixth decade (19), creates a thinner epidermis primarily because of retraction of rete
pegs (19), leading to an increase in the minimal thickness of epidermis with a concur-
rent decrease in maximum thickness (18,20). As a result, the dermal–epidermal
junction flattens by 35% (18,20).
The flattened dermal–epidermal junction, with its reduced interdigitation
between layers, results in less resistance to shearing forces and an increased vulner-
ability to insult (21). The smaller contiguous surface between the two layers creates
reduced communication between the dermis and epidermis and a reduced cellular
supply of nutrients and oxygen (18,30). Flattening also may be associated with
decreased potential for proliferation and may affect percutaneous absorption (19).
The flattening of the dermal–epidermal junction also increases the potential for
dermo-epidermal separation, facilitating wrinkle formation (21), a process that may
be a mechanism by which wrinkles form (18,30).

Dermal Changes
Dermal thickness decreases with age (19), with a decrease in vascularity and
cellularity (31). The perception of pressure and light touch stimuli also decreases,
due to a degeneration of pacinian and Meissner’s corpuscles. There is also a decrease
in the number of mast cells and fibroblasts (31). The amount of glycosaminoglycans
in the dermis declines with age (18,30), as does the amount of hyaluronic acid pro-
duced by fibroblasts (18,30) and the amount of interfibrillary ground substance (32).
Skin stiffness remains fairly constant until it decreases in the eighth decade of
life (33). Aging, however, is inevitably associated with a decrease in collagen turn-
over (due to a decrease in fibroblasts and their collagen synthesis) as well as elastin
(31). Elastin also has higher degree of calcification in aged skin, with an associated
degradation of elastin fibers (22). Collagen cross-links stabilize, whereas collagen
bundles become disorganized (31).
 350 M. A. FARAGE ET AL.

The loss of molecular integrity of the dermis leads to increased rigidity,

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decreased torsion extensibility (6,18) and diminished elasticity (4,8) (eroding faster
in females than in males) (8), with a concomitant increase in vulnerability to tear-
type injuries (6,18). Recovery from mechanical depression, in fact, is dramatically
altered; observed in only minutes in young skin, but requiring more than 24 h in skin
of aged individuals (6,18).
Confocal laser scanning microscopy (CLSM) and optical coherence tomogra-
phy (OCT) provides in vivo, cross-sectional images of skin layers. Images of aged
skin display a definite decrease in the maximal thickness of the epidermis as well
as a flattening of the dermal–epidermal junction (18,20). Below the basal layer,
CLSM showed a reflecting layer of fibrous structure (18,20). The location of the
layer was strongly associated with age, found much deeper in younger than in older
skin (18,20). OCT also showed a bright reflecting age-associated fibrous layer in the
dermis, believed to be the same layer, which may be a transition between papillary
and reticular dermis (18,20).
Ultrasound echogenicity revealed that although overall dermal echogenicity
decreases with age (19) there is a regional enhancement in lower dermis echogenicity,
called the dermal echogenic band (DEB), that thins with aging (19). In addition, a
subdermal low echogenic band (SLEB or SENEB), not seen in young skin, was
observed in aged individuals. This band increased in width in proportion to
age and sun exposure and was found to correspond to an area histologically
defined as elastoic, in a region especially prone to accumulate increased amounts
of water (19).

Hypodermal Changes
The overall volume of subcutaneous fat typically diminishes with age, although
the proportion of body fat increases until approximately age 70. Fat distribution
changes as well; that in the face, hands, and feet decreases whereas a relative increase
is observed in the thighs, waist, and abdomen. These changes, while possibly increas-
ing thermoregulatory function by further insulating organs, decrease the cushioning
function in the extremities, which leads to an increased risk of bedsores or podiatric
problems (26).

Toxicological Implications of Structural Changes

The cumulative structural changes that come with age, combined with a life-
time of cutaneous insult, make the elderly more likely than younger individuals to
have a wide range of toxicological issues with their skin (Table 2). In addition, eld-
erly patients often have impaired sensory function as well as dementia and loss of
memory, which can increase risk for toxicological injuries (34,35) For example, it
has been observed that in the elderly retention of oral instructions during an office
visit is often less than 50% (36), making accidental overdose of medications more
likely.
Treatments that are routine in younger patients may require modification in
the elderly (37) due to the elderly patient’s diminished ability to heal or cope with
skin failure (38). Traditional second-line therapies may be called for in early stages

Table 2 The toxicological=clinical implications of aging skin
Physiological change
Thinning of epidermis and dermis
Flattening of dermal papillae
Slowdown in turnover rate of epidermis;
decrease of ratio of proliferative to
differentiated keratinocytes
Decrease in elastin fibers in horny layer
Decrease in vascularity and supporting
351
structures in dermis
Decrease in vascular plexus, blunted
capillary loops
Changes in and loss of collagen
and elastin fibers
Impaired immune response
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Pathological change
Increased vulnerability to mechanical
trauma, especially shearing and friction
Increased risk of blister formation
Delayed cellular migration and proliferation
Decreased wound contraction
Loss of elasticity
Blood vessels fragile, easily broken
Decreased wound capillary growth
Loss of thermoregulatory ability
Decreased tensile strength, lower layers more
susceptible to injury
Delayed collagen remodeling
Impaired inflammatory response
Impaired delayed hypersensitivity reaction
Toxicological=clinical significance
Increased incidence of skin tears
Increased susceptibility of infection
Increased time to re-epithelialization
Longer healing times after
injury or surgery
Longer healing times after
injury or surgery
Lax skin, wrinkling, with loss of
self-esteem and=or depression
Skin easily bruised (Senile purpura)
Increased risk of wound dehiscence
Hypothermia, heat stroke
Increased risk of pressure damage
to elderly skin, decubitus ulcers
Longer healing times after injury
or surgery
Increased risk of severe injury
from irritants
Increased risk of severe injury
from irritants
(Continued)
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Table 2. Continued

Physiological change Pathological change Toxicological=clinical significance

Decreased production of cytokines Increased risk of severe injury

Impaired neurological responses
Decreased skin thickness
Decrease in numbers of Langerhans cells
Reduced sensation
Loss of cushioning and support
Loss of cushioning and support
Decreased vitamin-D precursor production
from irritants
Increased susceptibility to
photocarcinogenesis, false
negative delayed hypersensitivity tests
Increased risk of thermal or other
accidental injury
Increased risk of pressure damage, decubitus ulcers
Increased susceptibility to skin tears, bruising
Osteoporosis and bone fractures

352
Atrophy of sweat glands Decreased sweating Less ability to thermoregulate, Hypothermia
Dry skin, xerosis

Reduced stratum corneum lipids Decreased water-holding capacity Dry skin, xerosis
Structural changes in stratum corneum Altered barrier function Variable response to topical medications, altered
sensitivity to irritants

Reduced water movement from Decreased hydration of epidermis Dry skin, xerosis
dermis to epidermis

Decrease in melanocytes Loss of ability to tan, more susceptible Cutaneous neoplasms

to solar radiation
Graying hair Loss of self-esteem

Table summarizes findings from Boss & Seegmiller (55), Baranowski (56), Fletcher (57), Gilchrest (58), and Haroun (59)
 STRUCTURAL CHANGES OF AGING SKIN 353

of treatment (35). Safety concerns with any medication are accentuated in the
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elderly, due to the more fragile nature of their integument, the tendency for pro-
longed use in chronic skin conditions, the possibility of drug eruptions (39), and
the probability of polypharmacy in this population (38). Stronger medications
should be chosen only when therapeutic benefit justifies the risk (40).
Contact dermatitis is common in the elderly population (41), particularly
allergy-type reactions (42). Reduced ability to mount a delayed-type hypersensitivity
reaction (43) in the elderly decreases individual susceptibility to allergic contact
sensitivity due to a reduction in numbers of Langerhans cells (44), decreased T-cells,
and diminished vascular reactivity (43). However, decades of potential sensitization
(39) and an increased level of exposure maintains a presence of allergic contact
sensitivity in the geriatric population (44,45). The most common culprit in allergic
contact sensitivity is topical medications (46), in fact, as much as 81% of patients
being treated for chronic leg ulcers exhibit allergic reactions to topical medications
(44). Patch testing before the use of topical medications may be beneficial, especially
within high-risk populations like those being treated for dermatitis or ulceration
of the lower extremities (39). Testing should include medicaments and dressings,
as well as dental prostheses and medications for ocular disease (39). In the aged,
generalized allergic rash is far more likely to be due to medicines than to be food-
related (39). Occasionally an agent increases the patient’s sensitivity to the sun in
a phototoxic (photoirritant) reaction, or produces a hypersensitivity reaction upon
sun exposure (46).

ANTI-AGING THERAPIES
Estrogen Replacement Therapy (ERT)
The advent of ERT for menopausal women has documented clearly the pro-
found influence of endogenous estrogen on the skin. Exogenous estrogen, adminis-
tered to postmenopausal women, has demonstrated the ability to reverse or prevent
many of the processes of intrinsic skin aging.
In clinical trials, women on ERT consistently had greater skin thickness than
those not using ERT (4). A cross-sectional study using diagnostic ultrasound demon-
strated that the use of ERT normalized skin thickness levels to premenopause levels
(4). Although the increase in skin thickness was credited to an increase in dermal
connective tissue rather than epidermis, topically applied estradiol cream was shown
to produce an increase in epidermal thickness of 23% as well as a normalization of
rete peg patterns (4).
The reduction in dermal collagen associated with postmenopausal estrogen
declines is believed to be the main component of the skin atrophy that occurs with
aging, with a 30% loss in collagen occurring over the first five menopausal years (4).
Numerous studies, reviewed by Hall (2004) and Brincat (2005) and colleagues, have
demonstrated an increase in the collagen content of the dermis with the use of
exogenous estrogen replacement, with increases as substantial as 6.5% (4,47).
Studies have also demonstrated improvements in elasticity and skin laxity with
ERT, as well as substantial improvement in wrinkling, at least in women who did
not smoke (47).
 354 M. A. FARAGE ET AL.

Topical Anti-Aging Treatments

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With respect to interventions focused specifically on the cosmetic issues of

aging skin, topical medicines predominate for obvious reasons and have included
sex hormones, vitamins, and various topically applied skin components (48). Topi-
cally applied estrogen reverses many effects of both intrinsic and photoaging (4),
as does progesterone (18,49).Vitamin C (20) and A (20) (especially its derivative, reti-
nal) have also been employed with significant success. Topical application of an iso-
flavone emulsion derived from soy was demonstrated to reverse the loss of dermal
papillae at the dermal–epidermal junction (18,30) as well as significantly enhance
number of dermal papillae in age-atrophied skin (18,30).
Clinical testing of a topical vitamin B3 preparation, niacinamide, has demon-
strated significant efficacy against numerous undesirable consequences of aging skin.
Fifty Caucasian females between the ages of 40 and 60 were treated for 12 weeks in a
split-face study with a moisturizer with and without the addition of 5% niacinamide.
Niacinamide-treated skin showed significant improvement with regards to fine lines=
wrinkles, hyperpigmentation spots, texture, red blotchiness, and sallowness as com-
pared to skin treated with moisturizer alone (50). A facial moisturizer containing nia-
cinamide in combination with panthenol and vitamin E was also shown, in a 4-week
randomized, blinded, controlled study, to improve stratum cornum barrier function,
rehydrate skin, and improve the clinical signs and symptoms of rosacea (51).

Epidermal Stem Cells

Epidermal stem cells, the field of most interest in current anti-aging research
have recently been localized in the interfollicular epidermis. Frequency of these
long-term repopulating cells is approximately 0.01% of basal epidermal cells; how-
ever, 100-fold fewer than previously believed (52).

CONCLUSION
Despite the numerous and profound changes that occur over a skin’s lifetime,
the human integument remains relatively functional, particularly when protected
from environmental insult. Compared to youthful skin, however, the skin of older
subjects is compromised in many ways (9). Structural changes lead to undesirable
visible characteristics as well as a decreased elasticity and resilience, leaving the aged
skin susceptible to injury and disease.
As the population of the industrialized world continues to age, increased atten-
tion to the problems of aged skin, cosmetic and beyond, will improve the quality of
life in those years gained by previous medical accomplishments.

ACKNOWLEDGMENTS
The authors are grateful to Drs. S. McClanahan, Randy Nunn, Keith Ertel,
Don Bissett, and Joe Kaczvinsky for the critical review of this manuscript, to
Ms. Zeinab Schwen and Ms. Wendy Wippel (Strategic Regulatory Consulting,
 STRUCTURAL CHANGES OF AGING SKIN 355

Cincinnati, OH) for assistance in the preparation of this manuscript, and to

Downloaded By: [CDL Journals Account] At: 03:21 12 January 2008

Ms. Peggy Firth for the medical illustrations.

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