International Journal of Cosmetic Science, 2008, 30, 87–95
Review Article
Intrinsic and extrinsic factors in skin ageing: a
review
M. A. Farage*, K. W. Miller*, P. Elsner  and H. I. Maibachà
*The Procter & Gamble Company, Winton Hill Business Center, Cincinnati, OH, USA,  Klinik Fur Dermatologic,
Friedrich-Schiller-Universitat, Jena, Deutschland and àDepartment of Dermatology, University of California, San
Francisco, CA, USA
Received 25 May 2007, Accepted 24 September 2007
Keywords: ageing skin, genital skin, skin pigmentation, photodamage, UV exposure
Synopsis
As the proportion of the ageing population in
industrialized countries continues to increase, the
dermatological concerns of the aged grow in medi-
cal importance. Intrinsic structural changes occur
as a natural consequence of ageing and are geneti-
cally determined. The rate of ageing is significantly
different among different populations, as well as
among different anatomical sites even within a
single individual. The intrinsic rate of skin ageing
in any individual can also be dramatically influ-
enced by personal and environmental factors, par-
ticularly the amount of exposure to ultraviolet
light. Photodamage, which considerably acceler-
ates the visible ageing of skin, also greatly
increases the risk of cutaneous neoplasms. As the
population ages, dermatological focus must shift
from ameliorating the cosmetic consequences of
skin ageing to decreasing the genuine morbidity
associated with problems of the ageing skin. A bet-
ter understanding of both the intrinsic and extrin-
sic influences on the ageing of the skin, as well as
distinguishing the retractable aspects of cutaneous
ageing (primarily hormonal and lifestyle influ-
ences) from the irretractable (primarily intrinsic
ageing), is crucial to this endeavour.
Correspondence: Dr. Miranda A. Farage, The Procter &
Gamble Company, Winton Hill Business Center, 6110
Center Hill Road, PO Box 136, Cincinnati, OH 45224,
USA. Tel.: +1 513 634 5594; fax: +1 513 634 7364;
e-mail: farage.m@pg.com
ª 2008 Procter & Gamble Co. Journal compilation
ª 2008 Society of Cosmetic Scientists and the Société Française de Cosmétologie
Résumé
Comme le pourcentage de la population vieillis-
sante dans les pays industrialisés s’accroı̂t, les
préoccupations dermatologiques des personnes
âgées augmentent en importance sur le plan
médical. Les modifications structurelles intrinsè-
ques sont une conséquence naturelle du vieillisse-
ment et sont génétiquement déterminées. La
vitesse de vieillissement diffère significativement
selon les différentes populations et selon les différ-
ents sites anatomiques, même pour un seul indi-
vidu. La vitesse intrinsèque du vieillissement de
la peau pour un individu peut être aussi très
influencée par les facteurs personnels et environ-
nementaux, en particulier le taux d’exposition à
la lumière ultra-violette. La photodégradation
qui accélère considérablement le vieillissement
visible de la peau augmente également beaucoup
le risque de formation de néoplasme cutané. Au
fur et à mesure que la population vieillit, il faut
davantage se préoccuper de diminuer la morbi-
dité réelle associée au vieillissement de la peau,
plutôt que de palier à ses conséquences cosméti-
ques. Il est donc crucial de s’efforcer à mieux
comprendre les facteurs intrinsèques et extrinsè-
ques qui agissent sur le vieillissement de la peau
et aussi de faire la distinction entre les aspects
réversibles du vieillissement cutané (facteurs
essentiellement hormonaux et mode de vie) et les
aspects irréversibles (principalement le vieillisse-
ment intrinsèque).
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Factors in skin ageing
Introduction
Ageing is a process in which both intrinsic and
extrinsic determinants lead progressively to a loss
of structural integrity and physiological function
[1]. Intrinsic ageing of the skin occurs inevitably
as a natural consequence of physiological changes
over time at variable yet inalterable genetically
determined rates [2]. Extrinsic factors are, to vary-
ing degrees, controllable and include exposure to
sunlight, pollution or nicotine, repetitive muscle
movements like squinting or frowning, and miscel-
laneous lifestyle components such as diet, sleeping
position and overall health [2].
The demographics of the U.S.A. are changing
rapidly with respect to its elderly population; by
2030, one of every five Americans is expected to
be over 65 [3]. It is predicted that life expectancy
in the U.S.A. and other industrialized countries
will continue to increase, hitting 100 years by
about 2025 [4]. Women, with longer average life
expectancies than men, can expect to spend more
than one-third of their lifetimes in menopause [5].
The human integument, one-sixth of the total
body weight [6], forms the most visible indicator of
age. A sophisticated and dynamic organ, it serves
as a barrier between the internal environment and
the world outside, yet has numerous functions that
go far beyond that role [7] such as homeostatic
regulation, prevention of percutaneous loss of fluid,
electrolytes, and proteins, temperature mainte-
nance, sensory perception and immune surveil-
lance [6]. The synergistic effects of intrinsic and
extrinsic ageing factors over the human lifespan
produce deterioration of the cutaneous barrier [1],
with significant-associated morbidity. Aged skin is
susceptible to pervasive dryness and itching [8],
cutaneous infection [9], autoimmune disorders
[10], vascular complications [11] and increased
risk cutaneous malignancy [8]. In fact, most people
over 65 have at least one skin disorder, and many
have two or more [12].
One particular cohort of the American popula-
tion is proving particularly useful in defining the
separate roles of intrinsic and extrinsic factors in
skin ageing: the ‘baby boomers’, a generation pro-
duced by a post-World War II surge in the U.S.A.
birthrate between 1945 and 1965. Their arrival
coincided with the advent of widespread antibiotic
use (as well as universal progress in overall health
research), creating the first generation with a third
phase of life: the ‘golden years’ with the expecta-
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88
M. A. Farage et al.
tion of leisure time, preservation of youthful
appearance and good health [13]. The entrance of
the first baby boomers into middle age fuelled the
development of commercial products that could
reverse the signs of intrinsic skin ageing [13].
At the same time, however, the historically
sun-seeking behaviours of these baby boomers
have been implicated in a recent surge in skin
cancer rates [14]. It is estimated that 90% of all
skin cancers are directly related to sun exposure
[15]. About 90% of skin cancers are diagnosed at
or after the age of 45 [16]. Marked increases in
all skin cancer rates have been observed in the
last two decades or so, roughly coinciding with
the arrival of the baby boomer segment of the
population into middle age. Incidence of mela-
noma has doubled since 1985 [16], while in the
last few decades, the incidence of non-melanoma
skin cancers has also increased across the Wes-
tern world by varying but consistently alarming
rates. Reported increases in the incidence of basal
cell carcinoma in a given recent 10-year period
(depending on the study) were as high as 66%
(U.K.), although increased incidences as high as
93% (Australia) were reported for squamous cell
carcinoma [17]. Annual incidence of these non-
melanoma skin cancers exceeds the incidence of
any other cancer five fold [17]. It is often the aes-
thetically unwelcome sequelae of the intrinsic age-
ing of the skin that bring the patient to the
dermatologist’s office. Only 6% of dermatological
visits concern skin cancer [2]. Infinitely more
damaging to overall health, however, are the
extrinsic factors of skin ageing like ultraviolet
(UV) light exposure, which, unlike intrinsic fac-
tors, can be significantly modified.
Intrinsic skin ageing factors
Ethnicity
The greatest effect of ethnicity on ageing is primar-
ily related to differences in pigmentation. High lev-
els of pigmentation are protective with regard to
the cumulative effects of photoageing, with Afri-
can-Americans showing little cutaneous difference
between exposed and unexposed sites [18]. In
addition, if sensitivity is measured in terms of skin
cancer incidence, skin cancer rates between Cau-
casian and African-Americans indicate that pig-
mentation provides a 500-fold level of protection
from UV radiation [19]. Basal cell carcinoma and
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Factors in skin ageing
squamous cell carcinoma occur almost exclusively
on sun-exposed skin of light-skinned people [20].
African-American skin is more compacted than
Caucasian skin, as well as having a higher inter-
cellular lipid content, which may contribute to
more resistance to ageing [18]. Wrinkling in
Asians has been documented to occur later and
with less severity than in Caucasians, [21, 22]
although the reason for these observations was
not explored.
Anatomical variations
Huge variations in some skin parameters have been
observed with respect to the body site studied,
underscoring a need to standardize study site as
well as ages compared in order to obtain meaning-
ful results [23]. There are large differences in skin
thickness with respect to body site, ranging from
<0.5 mm on the eyelids to more than 6 mm on the
soles of the feet [24]. The decrease in epidermal
thickness with ageing was found to be smaller at
the temple than at the volar forearm [21, 25],
which may be the effect of cumulative photoageing.
The lipid composition of human stratum corne-
um displays striking regional variation in both
content and compositional profile [23]. There is a
much higher proportion of sphingolipids and cho-
lesterol in palmoplantar stratum corneum than on
extensor surfaces of the extremities, abdominal or
facial stratum corneum [23]. There is also an
inverse relationship between the lipid weight
percentage of a particular body site and its perme-
ability [23].
Skin rigidity is much higher at the forehead
than at the cheek in post-menopausal women
[26]. Also, in areas of the body with high blood
flow (e.g. lip, finger, nasal tip and forehead), blood
flow decreased with age [27] compared to areas
with baseline low blood flow, in which no differ-
ence was observed [27]. The decrease in sensory
perception with ageing is more pronounced in the
nasolabial fold and cheek, than in the chin and
forehead [23].
It is commonly assumed that aged skin is intrin-
sically less hydrated, less elastic, more permeable
and more susceptible to irritation [21, 26],
because of an apparently less complete functional
barrier than that in forearm skin [28] measured
by higher transepidermal water loss [21, 28]. Irri-
tant and permeability testing, however, have not
demonstrated increased susceptibility [21, 26].
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M. A. Farage et al.
Hormonal changes in cutaneous tissues
The topic of hormonal changes in skin, primarily
the effect of changes of oestrogen levels in the skin
of women, has been reviewed recently and com-
prehensively by many competent authors [5, 29–
33] and will therefore not be covered here,
although we have addressed this topic in other
publications [34, 35].
Vulvar skin, however, differs from that of the
bulk of cutaneous epithelium in that skin in the
vulvar area derives from three different embryonic
layers. The cutaneous epithelia of the mons pubis,
labia and clitoris originate from the embryonic
ectoderm and exhibit a keratinized, stratified struc-
ture similar to the keratinized, stratified skin at
other sites. The mucosa of the vulvar vestibule
originates from the embryonic ectoderm and is
non-keratinized. The vagina is derived from the
embryonic mesoderm and is responsive to oestro-
gen cycling [21, 26]. The morphology and the
physiology of the vulva and vagina thus undergo
numerous specific changes associated with hor-
monal changes at menopause [26].
After menopause, the following changes occur:
vaginal epithelium atrophies, cervico-vaginal secre-
tions become sparse, vaginal pH rises, atrophic vag-
initis becomes more common [21, 26], collagen
and water content decrease, pubic hair grays and
becomes sparse, the labia majora loses s.c. fat and
also the labia (labia minora, vestibule and vaginal
mucosa) atrophies. In addition, vaginal secretions
decrease and the thinned tissue is more easily irri-
tated and susceptible to infection [21, 26].
The cumulative effect of oestrogen deficiency con-
tributes to poor wound healing [5]. Skin collagen
content and thickness decrease with the hormonal
affects of castration [36]. Also dramatic hormonal
changes, particularly thyroid, testosterone and
oestrogen, alter epidermal lipid synthesis [23]. Atro-
phied genital tissue with limited mobility is more
susceptible to shear forces and may be more suscep-
tible to pH changes and enzymatic action [21, 26].
Vulvar skin is more resistant to tape stripping
and recovers more quickly in younger subjects
than in older ones [37]. Also, vulvar skin has an
increased rate of epidermal turnover [21, 30] and
increased basal cutaneous blood flow [21, 37].
Forearm skin has less frequent and slower reac-
tion to sodium lauryl sulphate irritation than that
in younger skin while no age-related differences
were observed in the vulvar area [38].
89
Factors in skin ageing
Permeability in the vulva is a complex issue,
affected by increased vulvar skin hydration, the
presence of hair follicles and sweat glands, cutane-
ous blood flow, occlusion and the properties of the
chemical in question [26]. Testing of vulvar perme-
ability of the aged vulva skin has yielded conflicting
results. Absorption of hydrocortisone in the vulva
was shown to be greater in aged skin [39], while
no age-related differences were observed in percuta-
neous absorption of testosterone [39]. In general,
the vulvar area is more hydrated, with a higher
coefficient of friction than other skin [21, 26]. For
an extensive review of permeability in the vulva
area, see a recent review by Farage et al. [40].
Elderly patients are, however, susceptible to con-
tact irritation dermatitis in the vulvar area,
because of urinary moisture under occlusion. Uri-
nary ammonia elevates local pH, which alters bar-
rier function, further compromising skin integrity
and increasing risk of infection [21, 26].
The vulvar area, because of sweating, occlusion,
vaginal discharge, friction, use of hygiene products
and incontinence, is increasingly susceptible to per-
sistent vulval itch and irritation in old age [41, 42].
There is a significant decrease in the size and
number of free nerve endings in aged skin in genital
mucous membranes with a corresponding decrease
in sensory perception in the genital area [21, 43].
Extrinsic skin ageing factors
Lifestyle influence
Skin is affected by ambient conditions such as tem-
perature and humidity. An increase in skin tem-
perature of 7–8 doubles the evaporative water
loss [44]. Low temperature stiffens skin and
decreases evaporative water loss even with plenty
of humidity in air, as structural proteins and lipids
in the skin are critically dependent on temperature
for appropriate conformation [44]. Some medica-
tions affect the skin as well, particularly hypocho-
lesterolemic drugs, which may induce abnormal
increased desquamation [45].
By far, however, the two greatest exogenous fac-
tors, both of which exact a heavy toll on skin, are
smoking [46] and exposure to UV light.
Effects of smoking and nicotine
Cigarette smoking is strongly associated with elas-
tosis in both sexes, [47] and telangiectasia (red
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90
M. A. Farage et al.
Figure 1 Effects of smoking on facial skin. Used by per-
mission from Lippincott, Williams and Wilkins.
spots on skin) in men [47]. Smoking causes skin
damage primarily by decreasing capillary blood
flow to the skin, which, in turn, creates oxygen
and nutrient deprivation in cutaneous tissues. It
has been shown that those who smoke have fewer
collagen and elastin fibres in the dermis, which
causes skin to become slack, hardened and less
elastic. Smoke causes damage to collagen and elas-
tin in lung tissue and may do so in skin as well
[47]. In addition, constriction of the vasculature
by nicotine [47] may contribute to wrinkling [36]
(Fig. 1).
Smoking increases keratinocyte dysplasia and
skin roughness [1]. A clear dose–response relation-
ship between wrinkling and smoking has been
identified [46], with smoking being a greater con-
tributor to facial wrinkling than even sun expo-
sure [47]. Smoking was demonstrated to be an
independent risk factor for premature wrinkling
even when age, sun exposure and pigmentation
were controlled [47]. In addition, although hor-
mone-replacement therapy was demonstrated to
reverse wrinkling, the skin of long-time smokers
did not respond [36]. The relative risk for moder-
ate-to-severe wrinkling for current smokers com-
pared to that of life-long non-smokers was 2.57
with a CI of 1.83–3.06 and a P < 0.0005 [36].
Wrinkle scores were three times greater in smok-
ers than in non-smokers, with a significant
increase in the risk of wrinkles after 10 pack-years
[48]. Pack-years are calculated by multiplying the
number of packs of cigarettes smoked per day by
the number of years the person has smoked [48].
For example, 10 pack-years would define both as
smoking one pack a day for 10 years, or two
packs a day for 5 years [48]. Smoking also
increases free radical formation and is an
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International Journal of Cosmetic Science, 30, 87–95
Factors in skin ageing
important risk factor in cutaneous squamous cell
carcinoma [47].
Exposure to UV light (photoageing)
Intrinsic changes occur in all skin as people age,
including decreased turnover, chemical clearance,
thickness and cellularity, thermoregulation,
mechanical protection, immune responsiveness, sen-
sory perception, sweat and sebum production and
vascular reactivity [21, 49]. These changes represent
a generalized atrophy with few structural alterations
up to the age of 50, followed by slow deterioration
[44]. In contrast, solar exposure to UV light initiates
a flurry of molecular and cellular responses that end
with a rapid dynamic disorder [44].
The effects of sunlight on the skin are profound,
and are estimated to account for up to 90% of visi-
ble skin ageing [21, 22], particularly in those
without the natural protection associated with
higher levels of melanocytes in the skin [18]. Sun-
light is composed of three different types of radia-
tion: UVC, UVB and UVA. UVC (100–290 nm) is
largely blocked by the ozone layer and has little
impact on skin [20]. UVB (290–320 nm) pene-
trates only into the epidermis and is responsible
for the erythema associated with a sunburn [20].
UVA requires 1000-fold higher levels of radiation
to cause sunburn, so it was long considered irrele-
vant to skin damage. It is now known that
because it penetrates into the dermis, UVA may be
responsible for most of the chronic skin damage
associated with photoageing [20].
Sunlight damages skin across a spectrum of
physiological processes. UV radiation in the dermis
causes a molecular chain reaction which ultimately
results in the upregulation, in both dermis and epi-
dermis, of matrix metalloproteinases which stimu-
late the production of collagenase, gelatinase and
stromelysin-1 in both fibroblasts and keratinocytes.
The result is a deterioration of both collagen and
elastin, as well as other components of the dermal
extracellular matrix. Repeated exposure to solar
radiation yields repeated, and increasingly faulty,
attempts to repair the dermal matrix, with a cumu-
lative effect on the structure and organization of its
collagenous foundation. Invisible flaws in the
repaired dermal matrix, with repeated cycles of
exposure, eventually become visible to the naked
eye in the form of sagging skin and wrinkles [50].
Ultra violet radiation also initiates damage to
the genetic material. UVB primarily acts to create
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M. A. Farage et al.
pyrimidine dimers that eventually result in muta-
tion through errors in DNA replication; UVA radi-
ation primarily initiates genetic damage through
the creation of reactive oxygen species or free radi-
cals [51]. Free radicals can also wreak havoc on
numerous cellular processes, e.g. facilitating the
upregulation of matrix metalloproteinases (dis-
cussed above) [51].
In addition, UV radiation acts indirectly to dam-
age skin by interfering with enzymes critical to the
DNA repair process, and by interference with com-
ponents of the immune system (specifically T cells
and Langerhans cells) that act to eradicate carcin-
ogenic cells [20]. It has recently been shown that
UV radiation may also act to prevent apoptosis in
sun-exposed cells, thereby potentially promoting
tumour development [52].
In this respect, UV radiation is a complete car-
cinogen, as it both initiates cancer through DNA
mutation and promotes cancer growth through
the inflammatory processes inherent in cumulative
UV exposure (Fig. 2) [21, 53].
Photoageing is the superposition of this solar
damage on the normal ageing process, defined spe-
cifically by damage produced in tissue by single or
repeated exposure to UV light, believed to account
for the vast majority of not only aesthetic effects of
skin ageing, but also clinical problems as well [21,
49]. Modern Western culture has promoted tanned
skin as healthy, resulting in steadily increasing
rates of skin cancer and prematurely aged skin
[21, 41]. Virtually all Caucasian Western individu-
als with normal recreational practices have sub-
clinical signs of skin damage by the time they are
15 years old [53], whereas skin changes start to
become discernible in unexposed skin in the early
30s [2, 21].
Figure 2 Surface melanoma.
91
Factors in skin ageing
Ultraviolet light induces photochemical changes
that can lead to either acute effects (e.g. erythema
or sunburn) or chronic effects (e.g. premature skin
ageing and neoplasms) [21, 41]. The clinical signs
of cutaneous photoageing include changes in visi-
ble colour, surface texture [21, 41] including early
appearance of dyschromia and lentigines, sallow
yellow colour, loss of normal translucency or pink
glow, gradual appearance of telangiectasia and
purpura [21, 41]. Textural changes include
increased roughness, frank keratoses and the
development of fine rhytides which progress to
deeper folds and creases [21, 41].
Corneocytes in sun-exposed areas become pleo-
morphic with increasing anomalies: retention of
nuclear remnants, loss of lines of overlap and
roughening of border edges [2, 54]. Also, UV radi-
ation alters the skin’s immune function systemi-
cally [20, 21]. Epidermal thickness increases, then
decreases, with an eventual loss of epidermal
polarity (orderly maturation) and increased atypia
among individual keratinocytes [20, 21].
Ultraviolet band A (UVA) light penetrates more
deeply. Although it does not cause pronounced ery-
thema, it may damage dermis more than UVB light,
particularly elastic tissue related to skin ageing
[44]. Changes in the dermis include the degenera-
tion of collagen and deposition of abnormal elastotic
material, seen as wrinkles, furrows and yellowing of
skin [20, 21]. With severe photodamage, the dermis
becomes a massive quantity of thickened, tangled
and degraded elastic fibres. Tightly packed collagen
fibrils replace elastic microfilaments, becoming
finally an amorphous mass [20, 21]. Damaged der-
mal tissue provides less support to its vasculariza-
tion, causing vessels to widen and become visible at
the skin surface as telangiectasia [44]. The decrease
in perfusion in aged skin is more pronounced in
photoaged areas [44]. It has recently been reported
that it may be UVA that is responsible for the bulk
of epidermal skin damage. UVA excitation of trans-
urocanic acid initiates chemical processes that
result in photoageing of the skin [55].
Although the primary effect of photodamage is
skin thickening, severe damage results more in
dramatic thinning [20, 21]. Sun damage creates a
state of chronic inflammation, with ongoing
release of proteolytic enzymes by inflammatory
cells, disrupting the dermal matrix [20, 21]. Irradi-
ated skin was observed to have a decreased capac-
ity for inflammatory response [21, 43]. UV light
also reduced the quantity of epidermal Langerhans
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M. A. Farage et al.
cells, while it induced proliferation of suppressor T
cells, facilitating tumour induction [21, 43].
Although plasma concentration of retinol increases
with age, within the epidermis, vitamin A is
destroyed by sun exposure [56].
With acute sun exposure, genes with reparative,
protective or apoptotic functions as well as stress
communication genes are rapidly activated [19,
57, 58]. Ageing strikingly increases the expression
of related genes when exposed to UV [59].
Ultraviolet exposure modulates expression of col-
lagen I, III and VI genes; heat shock protein 47
(Hsp47) genes and matrix metalloproteinase 1
(MMP 1), contributing to the general disruption of
skin structure. Collagen I is time- and age-depen-
dent, where it is reduced after a single UV expo-
sure in human skin in vivo [21, 22]. Photoageing
is associated with increased expression of MMP 1
and MMP 9 [21, 60].
Characteristics of photoageing when compared
to intrinsic ageing are in Table I.
Conclusion
As the senior segment of the population increases,
the challenge of gerontological dermatologists will
be to move beyond the current focus on the unwel-
come aesthetic aspects of skin ageing to an amelio-
ration of the significant discomfort produced by the
ageing of the human integument [45]. The ability
of exogenous oestrogen to halt and even reverse the
numerous external effects of skin ageing in post-
menopausal women speaks to the potential-to-affect
genuine improvement [5]. Useful therapies, how-
ever, will require a deeper understanding of the
influences of both intrinsic and extrinsic factors on
the molecular processes of cutaneous ageing.
Intrinsic ageing, though genetically determined
and inalterable, is not constant across different
populations or even different anatomical sites on
the same individual. However, the potential com-
ponents of extrinsic ageing, including nutrition,
tobacco use and exposure to solar rays, are virtu-
ally endless, thus resulting in a wide range of visi-
ble signs of aged skin even within genetically
similar individuals of the same age. Future
research will strive for better understanding of both
intrinsic and extrinsic influences on the ageing of
the skin, while defining the retractable aspects of
cutaneous ageing (primarily hormonal and lifestyle
influences) as opposed to the irretractable (primar-
ily intrinsic ageing). Optimally, clinicians will seek
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Factors in skin ageing M. A. Farage et al.

Table I Comparing photoageing to intrinsic ageing

Characteristic Photoageing Intrinsic ageing Reference

Overall
Metabolic processes Pronounced increase Slow down Soter [61]
Clinical appearance Nodular, leathery, blotchy Smooth, unblemished Glogau [62]
Coarse wrinkles, furrows Loss of elasticity, fine wrinkles Glogau [62]
Skin color Irregular pigmentation Pigment diminishes to pallor Rees [63]
Skin surface marking Markedly altered, often effaced Maintains youthful geometric patterns Gilchrest [20]
Onset As early as late teens Typically 50s–60s (women earlier Kligman [64]
than men)
Severity Strongly associated to degree Only slightly associated to degree Rees [19]
of pigmentation of pigmentation
Epidermis
Thickness Acanthropic in early stages Thins with ageing Takema [65]
Atrophy in end stages Lavker [66]
Proliferative rate Higher than normal Lower than normal Lavker [66]
Keratinocytes Atopic and polarity loss Modest cellular irregularity Kligman [67]
numerous dyskeratoses
Dermo–epidermal junction Extensive reduplication of Modest reduplication of lamina dense Gilchrest [20]
lamina dense
Vitamin A content Destroyed by sun exposure Plasma content of retinol increases Seite [58]
Dermis
Elastin Marked elastogenesis followed Elastogenesis followed by Kligman [67]
by massive degeneration, elastolysis – ‘moth-eaten fibres’
dense accumulations on fibres
Elastin matrix Massive increase in elastic fibres, Gradual decline in production of Hanson [56]
replacing the collagenated dermal matrix, only modest increase
dermal matrix in the number and thickness of elastic
fibres in the reticular dermis
Lysosyme deposition Increased Modest Gilchrest [20]
on elastic fibres
Collagen production Decrease in amounts of mature Mature collagen more stable in Lavker [66]
collagen degradation
Grenz zone Prominent Absent Lavker [66]
Microvasculature Abnormal deposition of basement Normal Gilchrest [20]
membrane-like material
Microcirculation Vessels become dilated, deranged Microvessels decrease, remaining Gilchrest [20]
vessels do not change
Inflammatory response Pronounced inflammation, No inflammatory response observed Gilchrest [20]
perivenular, histocytic-lymphocytic
infiltrate

Numbers in parentheses refer to citations in the reference list.

to lessen the effects of intrinsic ageing while at the
same time aim for avoidance of the extrinsic com-
ponents with a commitment to: (i) accept the fac-
tors that cannot be changed, (ii) treat the factors
that can be treated and (iii) have the evidence-
based ‘wisdom’ to know the difference.
Acknowledgements
The authors are grateful to Drs S. McClanahan,
Randy Nunn, Keith Ertel, Don Bissett, Joe Kaczvin-
sky for the critical review of this manuscript and
to Ms Zeinab Schwen and Ms Wendy Wippel (Stra-
tegic Regulatory Consulting, Cincinnati, OH, USA)
for technical preparation. This work was fully
funded by P&G.
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