Regulation of Sirtuin-dependent skin cell Senescence by dermatology-associated compounds

One of the main causal factors of skin aging is ultraviolet radiation as part of sun exposure. This radiation induces many changes at the molecular level that alter the proper function of skin biological processes, being cellular senescence(definition) one characteristic process included in this group. Senescence is a cellular state in which the cells enters an irreversible cell cycle arrest and develops a proinflammatory phenotype that contributes to tissue damage and aging. In this context, the aim of this thesis was to find compounds that both activate sirtuins and protect against UV-induced cellular senescence in human dermal fibroblasts. Among the 30 compounds tested, 8 compounds induced sirtuin activation, while 2 compounds protected against UV-induced senescence. Only one of these compounds had positive effects on both processes. Further charaterization of the compound revealed that the protection exerted by this compound against cellular senescence was mediated by SIRT1 activation. Besides, we observed that this compound activates autophagy(definition), one of the stress response pathways of the cell linked to increased longevity and regulated by SIRT1, among other factors. In conclusion, the caracterized compound has proven to be a good candidate as skin anti aging compound through its action on autophagy, sirtuins and senescence.