ANTI-AGEING 21


Innovative active fights Zombie cells for well-ageing


n Pascale Prouhèze, Jessica Guglielmi, Barbara Morand, Frédéric Maccario, Pierre-Gilles Markioli, Noëlle Garcia, Mélanie Mollet, Lionel Valenti, Emmanuel Coste – Exsymol, Monaco


Senescence is a cellular response characterised by morphological changes, a stable growth arrest (in order to prevent tumoral proliferation) and a change in the cell’s secretome. Indeed, senescent cells, called Zombie cells, produce a large amount of senescence-associated secretory phenotype (SASP) which is responsible for a pro-inflammatory response, for collagen degradation, for free radical production, and for the transmission of the senescent state.1


As a result, senescent cells tend to


accumulate with age and 20 to 60% of the skin cells are actually senescent.2 The senescence process may be


induced by several causes. Ageing is the most common phenomenon (after a certain number of division, a cell may go into senescence), but another frequent cause is stress, especially oxidative stress that induces inflammation. The combination of ageing and moderated inflammation caused by stress is called inflamm’aging, also known as “secret killer”. This progressive and insidious phenomenon has visible effects in the long term and prevents the skin from ageing well. When a cell is exposed to stress, there


are a few possible outcomes. It can be repaired, it can undergo apoptosis (the programme cell death) if it is too severely damaged, or it can undergo senescence. Apoptosis will induce a high energy


expenditure since the cell will have to be replaced and requires the division of a healthy cell. The same is true for necrosis, which consumes less energy but also requires the remaining healthy cells to replace the eliminated cell. These two processes cause a significant energy impact for the body, and therefore for the skin. Senescent cells still maintain their


production activities although in a degraded form. Senescence thus seems to be an acceptable compromise at a lower energy cost. However, senescence is a source of extensive and chronic inflammation as described before, the inflamm’aging. Scutaline (INCI name: Scutellaria


June 2020


baicalensis root extract) is an active ingredient made from the dried roots of the Scutellaria baicalensis, a plant traditionally used in Chinese medicine and naturally rich in two polyphenols: Baicalein and Wogonin that have been described to reduce SASP.3 Baicalein is an activator of the Nrf2 pathway. It thus provides strong anti- oxidative benefits by stimulating the production of anti-oxidants such as NADP(H): Quinone oxidoreductase 1 (NQO1) and glutathione.4 COX-2 inhibitor.5


Baicalein is also a prostaglandin (PGE2


It therefore inhibits ) synthesis and


participates in reducing inflammatory symptoms like redness and pain. Wogonin is a NFkB inhibitor that


provides potent anti-inflammatory benefits.6 It is also responsible for degrading HIF-1α (hypoxia inducible factor-1α) that is key for regulating the angiogenesis process that may limit inflammation and redness.7


Using


a patented extraction method, the concentration of these two molecules was maximised for stronger benefits to the skin. We focused on a strategy consisting of


slowing the entry of cells into senescence during ageing and also decreasing the


a Normal cells b SIPS cells


120 100 80 60 40 20 0


Normal cells


SIPS cells


ability of senescent cells to affect nearby healthy cells and to cause a chronic low- grade inflammation leading to skin premature ageing. In this paper, we will present how


Scutaline (referred to as ‘Scutellaria baicalensis root extract’) is able to meet our strategy to help the skin to age well.


Preventing stress-induced senescence Senescent cells present several specific markers such as an increased senescence- associated-ß-galactosidase (SA-ß-Gal) activity and have a local impact in the tissue due to the secretion of pro-inflammatory mediators and to an overproduction of MMP-1 that will lead to collagen degradation.2 In order to assess Scutellaria baicalensis


root extract’s ability to prevent senescence, human dermal fibroblasts were exposed to H2


O2


the presence or in the absence of Scutellaria baicalensis root extract. While the exposure to H2


O2 led to a


dramatic increase in the number of senescent cells as assessed by monitoring


for 2 hours and cultivated for 3 days in


*** -44%


SIPS cells Scutaline (0.1%)


Figure 1: Scutaline prevents stress-induced premature senescence (SIPS). NHDF were exposed to H2


O2


for 2h, and for 3 days in the presence or in the absence of Scutaline.


Senescent fibroblasts were observed (a) and quantified (b). Senescent cells appear in blue green. *** p-value<0.001 vs. SIPS cells, n=9-18.


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Senescent fibroblasts (%of SIPS)


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