Skin ageing detox system reacts to cellular senescence

 Indirect effects, through the production of enzymes, cytokines and interleukines, may also occur and will eventually translate into the degradation of macromolecules, chronic inflammatory reactions, chemoattraction and immunosuppression.  Depending upon the extent of damage they undergo, skin cells can take various decisional pathways.1 If the extent of damage is relatively low, cells will trigger a repair process to fix any deteriorated molecules or impaired metabolic pathways before resuming their normal functions.  If excessive damage is caused making it impossible (or too energyconsuming) to repair, cells will undergo organised cell death also called apoptosis. In that scenario cells will be eliminated. When the extent of damage is ‘medium’ – significant enough to overwhelm the repair machinery but not sufficient to command apoptosis – cells will become senescent. Upon entering senescence, cells will no longer divide into daughter cells. Senescence is thus a mechanism of protection or an adaptation to stress preventing cells from transmitting damage (genetic) to their progeny.  However, unlike apoptotic cells, senescent cells remain alive, metabolically active and they accumulate in the skin as we age.  The accumulation of senescent cells can cause a form of age-dependent endogeneous toxification of the skin.  A likely link between cellular senescence and ageing and age-related conditions is acknowledged by the scientific community.2,3

Cellular senescence contributes to the ageing process

Cellular senescence is a mechanism of adaptation that can be induced by various stresses. DNA damage, radiation, chemicals, inflammation, cigarette smoke and oxidative stress are among the triggers that can induce cellular senescence (Fig 1). Skin cells become senescent by ‘freezing themselves up’ in a state of nonproliferation. Yet, senescent cells remain metabolically active. In fact, upon the onset of senescence, cells will start secreting pro-inflammatory cytokines and proteases which are collectively known as the senescence-associated secretory phenotype (SASP) factors.4 The SASP is under the control of the synthesis regulator (transcription factor) called NF-κB that is itself rapidly activated as cells become senescent.5 NF-κB activation occurs by the release and degradation of the inhibitor IκB that otherwise keeps NF-κB latent in normal cells. Once activated, NF-κB migrates to the cell nucleus and begins the synthesis of numerous SASP factors. Secreted by senescent cells in the skin extracellular environment, the SASP factors may in turn trigger chronic inflammatory reactions, oxidative damage and degradation of extracellular matrix components. Senescent cells accumulate in skin with age and because of the SASP factors are thought to actively contribute to the skin ageing process.