Photoaging

Initially due to ignorance of its true pathophysiology and subsequently due to lack of an
appropriate word, chronic sun damage has been widely mislabeled in both the lay and medical
literature as aging, premature aging, or accelerated aging. Clinical features of actinically
damaged skin are listed in Table 144-3 and histologically contrasted with those of intrinsic aging
in Fig. 144-1.

A prominent feature of photoaged skin is elastosis, a process characterized histologically by

tangled masses of degraded elastic fibers that further deteriorate to form an amorphous mass
(Fig. 144-2). In addition, the amount of ground substance, largely composed of
glycosaminoglycans and proteoglycans, increases in photodamaged skin, whereas the amount of
collagen decreases, in part because of increased metaloproteinase activity and enhanced cytokine
release. In contrast with aged sun-protected skin that demonstrates hypocellularity,
photodamaged skin frequently displays inflammatory cells, including mast cells, histiocytes, and
other mononuclear cells, giving rise to the term heliodermatitis (literally, “cutaneous
P.1391inflammation due to sun―) (Fig. 144-3). Fibroblasts are also more numerous than in
sun-protected skin.

In contrast with chronologically aged skin, photodamaged epidermis is frequently acanthotic,

although severe atrophy also can be seen, displaying, in addition, loss of polarity and cellular
atypia. Also, there is a decrease in the number and function of Langerhans cells. Additional
changes are described in Table 144-3.

The relative severity of sun-induced cutaneous changes varies considerably among individuals,
undoubtedly reflecting inherent differences in vulnerability and repair capacity for the solar insult.
Photoaging occurs not only in fair-skinned individuals (skin types I and II) but also in individuals with
darker skin types III and IV with a history of ample past sun exposure. It usually involves the face, neck,
or extensor surfaces of the upper extremities most severely. Interestingly, the gross appearance of
photodamaged skin of individuals with skin types I and II differs from that of individuals with skin types
III and IV, the former generally showing atrophic and dysplastic skin changes with actinic keratoses and
epidermal malignancies rather than hypertrophic responses such as wrinkling, lentigines, and
coarseness. One study has noted that patients presenting with basal cell carcinoma are less wrinkled
than peers of similar complexion and degree of photodamage,55 suggesting that different factors
determine these two responses to chronic UV exposure

Wrinkling of photodamaged skin is exacerbated by cigarette smoking56 and possibly other

environmental factors. The apparent influence of sex on the prevalence of certain photoaging features
undoubtedly reflects different hair styles, patterns of dress, and nature of sun exposure (occupational
versus recreational) between men and women over the past several generations. Other sex differences,
such as epidermal thickness and sebaceous gland activity, and as yet unrecognized effects of circulating
sex hormones also may influence their development. The characteristic distribution of different lesions
is a complex function of relative sun exposure for different body sites, anatomic distribution of the
participating cutaneous structures (e.g., melanocytes and sebaceous glands), and other poorly
understood factors
The action spectrum for human photoaging has never been determined, and hence the relative
contribution of the various spectral bands within sunlight is unknown. There is no truly appropriate
animal model. In rodent skin, an elastosis-like condition can be produced by prolonged intense
irradiation with either a predominantly UVB or UVA source, but attempts to determine the action
spectrum for murine elastosis have yielded conflicting results.57,58 UVB photons are on average 1000
times more energetic than UVA photons and are overwhelmingly

responsible for sunburn, suntanning, and photocarcinogenesis following sun exposure,59 although UVA
also contributes to these end points.60,61 UVA is suspected of playing a proportionately larger role in
photoaging because of its minimally 10-fold greater abundance in terrestrial sunlight, far greater year-
round and day-long average irradiance, and greater average depth of penetration into the dermis
compared with UVB. Moreover, human skin exposed daily for only 1 month to suberythemogenic doses
of UVA alone demonstrates epidermal hyperplasia, stratum corneum thickening, Langerhans cell
depletion, and dermal inflammatory infiltrates with deposition of lysozyme on the elastic fibers.62
These latter changes have been interpreted to suggest that frequent casual exposure to sunlight
containing principally UVA, e.g., while wearing a UVB-absorbing sunscreen, eventually may result in
damage to dermal collagen and elastin in ways expected to produce photoaging.

Although the clinical manifestations of aging and chronic sun damage differ, in many instances these
differences are subtle. Initially, histologic changes in elderly sun-exposed skin were described by
experienced investigators as differing only in degree from those in elderly sun-protected skin at both the
light microscopic and electron microscopic levels. Many of the age-associated physiologic decrements,
such as slowed wound healing and loss of immunoresponsiveness, also appear to be accelerated in sun-
exposed skin. Furthermore, cells cultured from chronically sun-exposed skin sites differ from cells
cultured from sun-protected sites of the same donors in having shortened culture life spans, slower
growth rates, lower saturation densities, and altered responsiveness to retinoic acid,63 all changes also
observed as a function of advanced chronologic donor age. Only in recent decades have qualitative
differences in the dermal fibrous proteins and microvasculature of paired sun-exposed and sun-
protected sites been documented. On a theoretical level, several of the mechanisms known to be
involved in UV-mediated cellular damage are also postulated to underlie chronologic aging.32,64 These
include DNA injury and/or decreased DNA repair, oxidative damage, lysosomal disruption, and altered
collagen structure

Molecular mechanisms for some of the degenerative changes observed in photoaged skin,
particularly the enzymatic breakdown of collagen,65 have been tentatively identified, consistent
with the overall clinical appearance of photodamaged skin. It was shown that modest physiologic
doses of UVB activate the transcription factors AP-1 and NF-κB in human skin.65 In intact
human skin, even a suberythemogenic dose of UVB transcriptionally upregulates and activates
extracellular matrix-degrading metalloproteinases that are regulated by AP-1, including
collagenase, stromelysin, and the 92K gelatinase, in both keratinocytes and fibroblasts.66 There
is also a concomitant upregulation of TIMPs that limits further matrix degradation, although
TIMPs presumably are not completely effective in blocking cumulative damage to dermal
collagen.
Degradation of matrix proteins is aggravated by NF-κB–mediated induction of interleukin
(IL)-1 and tumor necrosis factor (TNF), two proinflammatory cytokines, leading to recruitment
of neutrophils and secretion of neutrophil collagenase.66 UV irradiation also downregulates
procollagen transcription through an as yet unknown mechanism, leading to decreased levels of
both type I and type III procollagen.66 Presumably, over many years, these events in
combination reduce the collagen content of skin and promote wrinkling.
Other studies using UVA irradiation and the hairless mouse model showed decreased activity of
the enzyme prolyl-hydroxylase that participates in posttranslational modification of collagen.67
In contrast with UVB, which renders collagen more susceptible to enzymatic degradation,
irradiation with UVA rendered dermal collagen more resistant to degradation, in part as a result
of increased cross-linking of the fibers.