Alterations of the pigmentation system in the aging process

Abstract

Human skin aging is a natural phenomenon that results from continuous exposure to intrinsic (time, genetic factors, hormones) as well as extrinsic factors (UV exposure, pollution, tobacco). In areas that are frequently exposed to the sun, photoaging blends with the process of intrinsic aging, resulting in an increased senescent cells number and consequently accelerating the aging process. The severity of photodamage depends on constitutional factors, including skin phototype (skin color, tanning capacity), intensity, and duration of sunlight/UV exposure. Aging affects nearly every aspect of cutaneous biology, including pigmentation. Clinically, the phenotype of age pigmented skin has a mottled, uneven color, primarily due to age spots, with or without hypopigmentation. Uneven pigmentation might be attributed to the hyperactivation of melanocytes, altered distribution of pigment, and turnover. In addition to direct damage to pigment‐producing cells, photodamage alters the physiological crosstalk between keratinocytes, fibroblasts, endothelial cells, and melanocytes responsible for natural pigmentation homeostasis. Interestingly, age‐independent diffuse expression of senescence‐associated markers in the dermal and epidermal compartment is also associated with vitiligo, suggesting that premature senescence plays an important role in the pathology.

Skin Aging, Cellular Senescence and Natural Polyphenols

“…In this regard, UVB-triggered mTOR signaling, subsequently suppressing autophagy, participates in the upregulation of MITF activity, resulting in melanin production [ 257 ]. On the other hand, a senescent phenotype of age-spots-derived keratinocytes could be attributed to intracellular melanin accumulation, since keratinocytes display reduced melanosome degradation via autophagy impairment [ 258 , 259 ].…”

“…Senile lentigo, also known as age spots, is one of the major signs accompanying wrinkling during the aging of skin. Irregular pigmentation might be attributed to the hyperactivation of melanocytes, altered distribution of pigment and turnover [ 259 ]. The accumulation of lipofuscin in senescent cells also contributes to the occurrence of age spots [ 280 ].…”

“…Pigmentation is considered an outcome of the interplay between melanocytes and neighboring cells, such as keratinocytes and fibroblasts [ 288 ], and both aging and photoaging appear to significantly alter this system ( Figure 6 ). In particular, the development of senescence in keratinocytes and the impaired functioning of autophagy results in a prolonged epidermal retention of melanosomes [ 259 , 289 ]. Interestingly, in a 3D organotypic skin model, the incidence of photo-aged fibroblasts resulted in increased melanogenic gene transcription, increased epidermal melanin and hyperpigmentation [ 290 ].…”

The potential skin‐lightening candidate, senolytic drug ABT263, for photoageing pigmentation

“…Photoageing‐related pigmentation such as senile lentigo demonstrates the accumulation of senescent fibroblasts in the dermis 3 . A pivotal role of photoaged fibroblasts in determining the pigmentation phenotype of ageing skin has been highlighted 4 . Senescent fibroblasts crosstalk with melanocytes, with the phenotypic change of fibroblasts playing an important role in the stimulation of melanogenesis 5–7 .…”

Focus on the Contribution of Oxidative Stress in Skin Aging

“…Photoaging accounts for approximately 80% of facial aging [ 96 ]. Except for pigmentation, which presents the opposite feature in chronological aging (hypopigmentation) [ 85 , 97 , 98 ] and in photoaging (hyperpigmentation) [ 99 , 100 ], intrinsic and extrinsic skin senescence demonstrated several types of overlapping pathogenic molecular signaling. The common feature of both types of cutaneous aging is the generation of ROS, impacting DNA, protein, and lipid damage and the disorganization of the ECM [ 101 ].…”