Etiology

Wrinkles occur progressively on the skin surface, secondary to a variety of intrinsic and
extrinsic factors. [11] Epidemiologic studies have demonstrated that age, the number of
pack-years smoked, and UV exposure independently contribute to wrinkle formation
and premature skin aging. [7] [12] [13] Thin skin, paucity of subcutaneous fat, and gender
play an important role in the overall severity of wrinkles.
Physiologic chronologic skin aging is the main etiology of wrinkles, although genetic
factors may influence the location and shape of facial creases. The role of genetically
programmed chronologic aging is controversial. However, evidence can be found in the
literature that human aging has a hereditary component, and that the age of onset and
rate of progression of skin aging largely depends on genetic factors. [14] [15] Intrinsic aging
is an inevitable, genetically programmed process, of unclear underlying mechanism, for
which no prevention is available. [16] Moreover, the natural aging process first appears
as invisible changes at the level of the DNA.
Extrinsic aging is a dynamic process, influenced by such factors as chronic sun
exposure (the major environmental factor contributing to photoaging and secondary
wrinkle formation), smoking, poor nutrition, excessive alcohol consumption, a low BMI,
and pollution.
Cigarette smoking is a significant exogenous factor linked to increased facial wrinkling
and accelerated aging of both sun-exposed and protected areas of skin. [7] [17] [18] The
cumulative tobacco dose has been shown to significantly influence both the number of
elastic fibers and the percentage of the area these fill in the reticular dermis. [17]
Hyperdynamic muscular facial activities and progressive loss of underlying soft-tissue
support may also induce skin folds and accentuate cutaneous laxity and wrinkling.
Repetitive contractions of muscles responsible for facial expression pull directly on the
overlying tissues, causing the skin to fold and develop dynamic lines. image Among the
first lines to develop (by the third decade) are the horizontal forehead creases, caused
by contractions of the frontalis muscle, and the lateral canthal or "crow's feet" lines,
caused by contractions of the orbicularis oculi muscle. image Glabellar frown lines
develop at variable ages as a result of the pull of the procerus and corrugator
muscles. [11] Chronic contraction of the orbicularis oris muscle induces folds and lines
around the mouth, perpendicular to the vermilion border, which become more noticeable
in the fifth decade. Forceful contraction of the zygomaticus muscles contributes to the
formation of the nasolabial folds.
Pathophysiology
Advanced age and solar damage are the most important factors leading to wrinkle
formation. The changes associated with chronologically aged skin are distinct from
those resulting from sun exposure.
As in all tissues and organs, the skin undergoes characteristic alterations with advanced
age. Morphologic changes associated with chronologically aged skin result in cutaneous
laxity and fine wrinkling, and become evident primarily on the face. Aging skin
demonstrates a progressive loss of thickness, beginning with a thinning of the epidermis
and the flattening of the dermoepidermal junction. Significant alterations leading to
atrophy mainly occur in the dermis. [19] The total number of fibroblasts, and the amount
of ground substance and eosinophilic material decreases with age. [11] [20] Progressive
reduction of the elastic fibers and changes in collagen components result in decreasing
cutaneous tensile strength. [21] The dermal microvasculature progressively diminishes
and reduced sebaceous gland activity contributes to an increase in skin
dryness. [11] [22] These histologic changes make the skin inelastic, lax, and prone to
wrinkling. Subcutaneous tissues (fat, muscle, bone) also demonstrate progressive
atrophy with age, causing the overlying skin to hang from points of deep attachments,
and contributing to further accentuation of skin folds. Gravitational lines represent the
combined influence of atrophy and gravity on aged skin. They become more obvious
between the ages of 40 and 50 years, and occur throughout the face and neck. [23] image
Photoaging does not accelerate the normal aging process, but the effects of UV
radiation superimpose upon those of aging, and many of the skin alterations that decline
with age show an accelerated decline in photodamaged skin. [24] image
Fair skin phototypes are more susceptible to chronic actinic damage and photoaging.
Skin types I to III on the Fitzpatrick classification consistently exhibit greater risk for
developing the long-term effects of sun exposure. [10] Actinic damage caused by UV-A
and UV-B injury to the dermis and epidermis results in the impairment of skin collagen
and elastin organization, and accentuates wrinkling over sun-exposed areas of the
body. [25] The most striking feature of chronic actinic damage is dermoelastosis,
characterized by the presence of massive quantities of thickened elastic fibers in the
dermis. Histologic changes include disorganization of collagen bundles and clumping of
elastic fibers, as well as an increase in the number of inflammatory cells and in melanin
production. The skin progressively becomes atrophic, inelastic, lax, dyspigmented with
a yellow hue, and wrinkled with telangiectasia, a leathery appearance, and cutaneous
malignancies.
The mechanisms responsible for the deleterious effects and cutaneous alterations
associated with cigarette smoking are not clear. Smoking causes a marked reduction in
the production of new collagen, the main structural protein of the skin, which maintains
skin elasticity, [26] [27] and may acutely decrease arteriolar blood flow in the cutaneous
microcirculation, resulting in chronic ischemia of the dermis. [28] It has also been
hypothesized that smoking decreases vitamin A levels, which protect against oxygen
radicals (oxidation) that damage DNA and connective tissue. [29] Tobacco smoke in the
environment promotes dryness of the skin surface and reduces blood flow to the skin,
resulting in the depletion of oxygen and essential nutrients. [30] [31] [32]
Exposure to air pollution may start a cascading process that results in the formation of
free radicals. Free-radical damage causes wrinkles by activating metalloproteinases
that break down collagen.