Longevity mechanisms have been largely studied for a decade. However, solutions still need to be found to extend, especially, skin longevity. The objective of this study was to develop a natural cosmetic solution able to extend skin healthspan, i.e. the optimal functioning of skin cells over time to maintain skin quality. Schisandrins were identified as specific lignans able to act on longevity mechanisms1,2. Thus, an active enriched in these molecules was developed from Schisandra chinensis berries. Screening was performed on 2D and 3D models, in basal or stressed conditions, to assess its preventive action on skin healthspan and decipher its mechanisms of action. Expected skin benefits were studied clinically on 24 Caucasian and 31 Asian pollution-exposed volunteers for 21 days, and on 40 unexposed Caucasian volunteers for 28 days vs placebo (split-face). Cellular results showed that Schisandra extract (SchE) significantly increases longevity genes SIRT6 and FOXO3, overexpressed in centenarians3,4, as well as autophagy and mitochondrial activity. SchE preserves skin barrier and prevents oxidative stress and inflammation induction in stressed 3D models. Clinically vs. placebo, SchE significantly increases skin microcirculation (+33%* at D14) and brightness (+47%*** at D21). Moreover, at D28 it smoothes skin (rugosity*: -4,1%), limits wrinkle number (-10,8%*) and improves skin dynamic elasticity (recovery time: -16,8%*). Skin surface protein carbonylation was also significantly reduced after treatment. Interestingly, a significant correlation was found between this result and the observed decrease of rugosity. An innovative method, based on the measurement of the most tensed facial position, proved SchE ability to prevent wrinkle formation and worsening (-16,4%*). Longevity is the result of interconnected biological activities optimal functioning, that is why SchE has a multi-action on cellular and tissular mechanisms. It is a potent natural solution for skin healthspan extension. This was confirmed in vivo underlying the power of schisandrins on skin longevity.