Cellular Senescence in Skin as an Early Sign of Aging

We reported that skin inherently possesses mechanisms to remove senescent cells. In the epidermis, this is achieved by the binding of JAG1, a Notch ligand expressed on adjacent non-senescent keratinocytes, to Notch1 receptors expressed by senescent keratinocytes, which promotes the exclusion of senescent cells from the basal layer by inducing differentiation. Meanwhile, in the dermis, senescent cells are phagocytosed by macrophages through recognition by the phosphatidyl serine (PS) receptor STAB1. However, since ageing is associated with the accumulation of senescent cells in skin tissue, it is hypothesized that this accumulation is preceded by a decline in the ability to remove them. Here, we tested this hypothesis by analysing in detail the changes in the number of senescent cells and the ability of them to be removed from the skin with ageing. Marginal skin tissues at the time of surgery were collected from patients who had provided informed consent. Paraffin-embedded sections prepared from the unexposed skin tissue were subjected to immunostaining with the major senescent cell marker p16INK4A to analyse the number of senescent cells. To characterize the ability for senescent cells to be removed from the skin, the expression of JAG1 in the epidermal keratinocytes and STAB1 in macrophages was analysed. The results confirmed that senescent cell accumulation was increased with age in both epidermis and dermis. We also found that the ability to remove senescent cells d...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs