Intrinsic or chronological aging occurs in all organs and cells in the body, including skin, and some of the major processes that are involved span cellular senescence, decreased metabolic capacitance, and diminished repair processes, including DNA repair as well as stress response [38].
The summation of these alterations in skin leads to clear physiological changes that can be observed as fine wrinkles, dryness, sallowness, and loss of elasticity. At the cellular level, there is a decreased proliferation pattern of epidermal keratinocytes and reduction in thickness of the dermis, which correlates with reduced collagen synthesis by dermal fibroblasts and aberrant melanogenesis from melanocytes. These changes not only lead to a general thinning of the skin but also impact the response to external insults and changes in the skin’s physical properties, including loss of elasticity. For example, elderly skin is more susceptible to sunburn from acute UV exposure and wound healing is significantly impaired, rendering the skin more prone to injuries such as tears, ulcerations, and infections. Underlying these changes is a general onset of senescence in fibroblasts—one of the primary theories of aging—that may be correlated to telomere length, which serves as a “mitotic clock” [39]. Compounding these changes in female skin is also the effect of hormonal changes that can impact the general physiology of skin. Changes in estrogen levels have been associated with decreased collagen synthesis and these changes, including wound healing response, may be overcome by hormone replacement therapy in the elderly [40].
In the epidermis, the turnover rate is typically found to be extended, increasing up to 40 days in the elderly and a general thinning of the skin is observed. In younger-aged skin, the thickness of the epidermis is 35-50 p, m, whereas in elderly skin it decreases to 25-40 p, m. However, the relative number of cellular layers remains intact. Water retention potential is also diminished in elderly skin, which can be observed as having more incidence of dry skin conditions than younger-aged skin [41]. The number of active melanocytes decreases by about 10-20% per decade, probably explaining in part the increased vulnerability to UV radiation in old age [42]. The remaining melanocytes are sometimes observed to increase in size and are irregularly dispersed, potentially explaining the appearance of age spots in elderly skin, particularly in photodamaged skin [43 ] . The number of Langerhans cells decreases as a function of age but activity is also affected by free radical damage from UV exposure, further compromising wound healing and prevention of infections.
In older-aged skin, the undulations of the rete ridges in the BMZ extending from the dermis into the epidermis are less noticeable, leading to a general flattening of the basement membrane interface. This is thought to be part of the reason that elderly skin is more fragile to tears and blistering as well as overall wound – healing responses.
In the dermis, one of the most significant changes that can be observed as a function of aging is a general thinning of the ECM content. As the ECM is such a large percentage of the thickness of the dermis, this can quite easily be observed at a gross morphological level.
The overall thickness is estimated to decrease by 20% on average in nonphotodamaged areas. In areas with photodamage, this decrease is often higher due to the combination of the aging process and UV-induced chronic changes. The loss of ECM content in the dermis is primarily due to a decrease in the synthesis of new type I and III collagen from fibroblasts as well as an increase in MMP expression levels and aberrant TIMP regulation [44]. This net imbalance would cause the loss of collagen content, particularly in the papillary region where dermal fibroblasts undergo a steady progression into senescence [45]. There is also a loss of blood vessel networks, which can impact the coloration of skin and limit metabolic processes due to nutrient distribution and waste removal. The decreased levels of new collagen synthesis and the increase in degradation via proteolytic processes and nonenzymatic cross-linking modifications such as glycation contribute to the appearance of fine lines and wrinkles as well as sallowness. Of more relevance in elderly skin, the ability to repair following a wound event is compromised as well.