144 SKIN CARE


Clearing senescent cells for rejuvenated skin


n Franziska Wandrey, Daniel Schmid, Fred Zülli – Mibelle Biochemistry, Switzerland


Fibroblasts in the dermis are responsible for the production of collagen to form the connective tissue, as well as for assisting in the wound healing of the skin. When these fibroblasts either age by telomere shortening through too many cell divisions or encounter too much oxidative stresses, such as UV light and pollution, which cause damage beyond repair, they face a choice. They can either continue to divide despite the accumulated damage that would be propagated to their daughter cells, which potentiates the harmfulness. A second option is to undergo apoptosis, programmed cell death, to stop themselves from spreading the damage. However, there is a third option, which permanently blocks the cells from undergoing further cell divisions: the cells become senescent. Senescent cells are also called ‘zombie cells’1


for the following reason: whilst


they no longer divide, they are also far from being dead. Senescent cells block an intracellular pathway that promotes their apoptosis in order to prevent their own elimination. Moreover, they continue to secrete signalling molecules such as cytokines that promote inflammation and can influence surrounding cells into also becoming senescent (Fig 1).2


In younger tissue,


senescent cells are usually cleared by the immune system. In aged skin and skin that has been exposed to consistent stress, the large number of senescent cells can no longer be cleared by the immune system without help and they therefore accumulate. The resulting chronic inflammation exacerbates the ageing process by promoting collagen degradation, which leads to a lack of skin elasticity. Not surprisingly, the formation and accumulation of senescent cells is one of the hallmarks of ageing.3


As a result, eliminating


senescent cells has emerged as a promising anti-ageing therapy in the medical field in the past few years.


Senolytic drugs to promote longevity A novel concept known as ‘senolytics’ helps to clear tissues of senescent cells in order to reduce inflammation and rejuvenate the tissue. The term senolytics was coined in 2015 by researchers from the Mayo Clinic


PERSONAL CARE EUROPE Abstract


Cellular senescence is one of the hallmarks of ageing. Senescent cells that reside in the dermis as a result of the ageing process and oxidative stress, secrete pro-inflammatory factors that further contribute to ageing. Therefore, eliminating senescent cells has emerged as a promising anti-ageing therapy in the medical field in the past few years. This novel concept known as ‘senolytics’ helps to clear tissues of senescent cells without affecting healthy cells in order to reduce inflammation and rejuvenate the tissue. For the first time, this concept has been adapted for cosmetics. An extract from organic alpine rose leaves demonstrated a clear senolytic activity on senescent fibroblasts. In placebo-controlled clinical studies, the alpine rose extract prevented the formation of protein carbonyls, one of the most harmful irreversible modifications of proteins, upon UVA irradiation. In addition, treatment with alpine rose extract significantly reduced skin redness and increased elasticity.


Figure 1: Schematic representation of a senescent fibroblast in the dermis. Secretion of cytokines by these senescent cells leads to constant inflammation in the skin, which results in collagen degradation and accelerated skin ageing.


and the Scripps research institute in the US, who described a mechanism through which senescent cells are selectively eliminated without harming healthy dividing cells.4


The


targeted senescent cells are going into apoptosis and are subsequently cleared from the tissue. Clearing senescent cells


both reduces negative effects of ageing pathologies and extends median lifespan.5 Despite being a brand-new life science topic, there have already been more than 200 scientific publications that investigate the senolytic activity of numerous compounds. So far, the concept of


April 2020


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