Melanocytes are the Only Epidermal Cells to Show Signs of Senescence with Aging

Lingering senescent cells arise in every tissue, and their presence is a cause of aging. These errant cells secrete a potent mix of molecules that rouse the immune system to chronic inflammation, degrade tissue structure, and change the behavior of surrounding cells for the worse. The more senescent cells, the worse the effects. Researchers are beginning to look more closely at cellular senescence in aging skin, and the results from the study noted here are particularly interesting. That melanocytes are the only skin cell type to show the canonical signs of senescence is unexpected.

Nonetheless, the negative effects of senescence still exist in this case, and reinforce the expectation that senolytic drugs that reach the epidermis sufficiently well will be capable of reversing skin aging to some degree, just as they have been shown to reverse measures of aging in other organs. Given the present state of knowledge, I expect the benefits of senolytic therapies on skin to be minimal until later life. The skin aging that occurs between 20 and 50 is probably not driven to any great degree by senescent cells, as senescent cell burden most likely scales with age in a similar manner to cancer risk. There will no doubt be clinical trials in the years ahead, and firm numbers where today there are only expectations, but skin aging isn't all that high on the priority list for most of the companies and research groups working in the field.

Over time, cells in the body can be damaged by external exposures, like ultraviolet radiation from the sun, or internal ones like oxidative stress. On the skin this appears as wrinkles, dryness, or age spots. In the skin, changes occur so the outermost layer called the epidermis gets less nourishment, becomes thinner and is easier to breach. To understand this process on a cellular level, researchers began looking at different cell populations in skin to see if any cell type was associated with skin damage more so than another.

The team initially thought that one type of cell that is abundant in skin and divides often, called keratinocytes, would drive senescence. However they report that melanocytes, the cells which produce the pigment responsible for skin color, fit the senescence profile and released pro-inflammatory factors that could affect surrounding cells and induce skin aging. "Melanocytes divide very little throughout our life and constitute 5-10% of the cells in the basal layer of the epidermis. They showed a variety of molecular markers of cellular senescence in the aging skin. We found that melanocytes became senescent without telomere shortening, which is not surprising since they hardly divide. But melanocytes showed DNA damage specifically at telomere regions irrespectively of their length due to oxidative stress."

To confirm that melanocytes were really the driver of skin aging, the team built a 3D human epidermis in the lab, and found that melanocytes alone could induce several features of skin aging in the model. They also reported that the effect of the senescent melanocytes could be moderated by treating the model with the senolytic drug ABT-737 or by the mitochondrially targeted antioxidant MitoQ that protects mitochondria.