Aging of Skin and Senescent Cells

“As we age, there are major changes in skin that are being addressed by many cosmetic companies as well as biomedical researchers. From an evolutionary viewpoint, a species is better able to adapt to environmental challenges if individuals die after their peak reproductive age. Thus, aging and death are programmed, and the issue is how to maintain a good quality of life while delaying the inevitable. One hallmark of aging is cell senescence, which is a cell state like the transformed cell state in that senescence can occur in cells from many different tissues. Senescent cells are characterized by a lack of growth, increase in cell size, and the senescence associated secretory phenotype (SASP) which is a complex cocktail of proteins secreted by senescent cells that can induce senescence in neighboring cells. Aged skin fibroblasts produce a similar cocktail of inhibitory molecules that appear to be skin specific6. It is expected that a negative feedback cycle can occur with increased levels of senescent cells causing further senescence. One strategy to combat aging is to kill the senescent cells with senolytic treatments to cause apoptosis of senescent cells 19. There appear to be benefits to the killing of the senescent cells but the treatments have not reached the clinics 20.

The biochemical basis of the senescent phenotype is not known but there are dramatic changes in mitochondrial fusion with senescence that indicate that increased fusion of mitochondria will cause senescence21. Thus, in both the transformed and senescent cell states, mitochondria and their mechanical properties appear to play prominent, although different roles.

In the case of aging skin, the quasi-steady state of skin thickness and tension changes with time and aging. With the constant turnover of skin cells every two to four weeks, there is the chance for remodeling to accommodate the changes in the dermis. The decrease in activity with age favors senescence of the fibroblasts; however, the magnitude of the strain with mechanical activity has important effects. In the case of normal skin fibroblasts, periodic strains of 20% can inhibit growth 22 whereas periodic strains of 3-7% can stimulate growth of primary fibroblasts 23. Further, in the case of aged skin fibroblasts, preliminary studies (Cui et al., unpublished results) indicate that 10% periodic strains cause a dramatic increase in cell area relative to young fibroblasts. This highlights the need to analyze a range of parameters for the cells of interest to know what level of physical activity can be beneficial.”