Senescent Cells in Senile Lentigo Caused by UV Exposure
Senile lentigo, an age spot, is a form of photoaging in response to UV exposure featuring a darkening of the skin. An increased burden of cellular senescence is thought to play an important role in photoaging more generally, and here researchers show that age spots contain an increased number of senescent cells. It is likely that these senescent cells are an important driver of the altered structure of skin and altered behavior of skin cells in an age spot. It is also likely that intermittent use of senolytic drugs will slow skin aging and even improve function in already aged skin, based on research conducted to date, but there is surprisingly little published human data on this front despite a number of companies offering plausibly senolytic skin products, and the growing off-label use of senolytic drugs such as dasatinib and quercetin.
In the dermal and epidermal layers of the skin, various manifestations of aging have been associated with an accumulation of senescent cells, namely fibroblasts, keratinocytes, and melanocytes. We and others have previously reported an accumulation of senescent cells in chronologically aged epidermis upon exposure to chronic low-dose UV radiation and in the epidermis of precancerous actinic keratosis, age-associated lesions that frequently occur in sun-damaged skin. Since the prevalence of photoaging in Asian populations commonly results in skin hyperpigmentation, we here extended our investigation to senile lentigo (SL), a common age-associated hyperpigmentation disorder caused by chronic UV exposure.
Facial skin biopsy samples from 9 donors of Korean ethnicity, classified under type III or IV on the Fitzpatrick scale, were collected from both perilesional and lesional sites. Expectedly, we observed a higher degree of pigmentation and more melanocytes. To determine whether SL lesions are associated with an accumulation of senescent cells, we stained sections for well-characterized hallmarks of senescence: p16INK4A, lamin B1, and increased nuclear size.
Using these markers we found an accumulation of senescent cells in SL epidermis. This is of particular interest because we and others have previously observed an accumulation of senescent keratinocytes in actinic keratosis lesions and in chronically UV-exposed skin. Moreover, it is noteworthy that patients with Hutchinson-Gilford progeria, a premature aging syndrome caused by an altered form of lamin A that triggers cellular senescence, exhibit widespread hyper- as well as hypopigmentation. However, the extent to which different cell types within the skin contribute to this phenotype remains unclear. Importantly, while the senescence-associated secretory phenotype in senescent human fibroblasts is well characterized, very little is known about the senescence-associated secretory phenotype in keratinocytes.