Cellular senescence inhibition halts skin ageing

The existence of a molecular clock is suggested, marking the moment when the capacity of cell replication stops and senescence starts. This marker is placed on the DNA molecules located at the ends of chromosomes, called telomeres, a term which comes from the Greek word “telos” (end) and “meros” (part). Each time a cell divides, its telomeres are shortened, thus reducing their subsequent cellular replicative capacity. In the 1990s it was established that the start of replicative senescence is controlled by a shortening of the telomere.

Cellular senescence in fibroblasts and skin ageing

The major cell type in the dermis is the fibroblast, a cell that synthesises protein products, such as the extracellular matrix, and connective tissue fibres, such as collagen and elastin. These proteins are responsible for the proper integrity and elasticity of skin as an organ. Senescence of fibroblasts is the main process of loss of fibroblasts in the skin and is closely related to ageing. During their lifetime, fibroblasts undergo a slowing down process of their cell duplication cycle until, after a certain number of cell divisions, they enter a state of cellular senescence until they die. Senescent fibroblasts suffer important metabolic and morphological changes, with alterations in the synthesis of components of the extracellular matrix, an increase in the synthesis of proteases and an increase in the secretion of proinflammatory cytokines. All these changes have a clear negative effect on skin tissue, causing skin ageing. It has been demonstrated that the number of cell duplications of fibroblasts depends on age. Fetal fibroblasts can duplicate approximately 50 times on average before entering senescence, while from 30 years of age onwards, the number of duplications is reduced by approximately 10% every decade, as shown in Figure 1.1