The alkaloid centcyamine increases expression of klotho and lamin B1, slowing the onset of skin ageing in vitro and in vivo

Abstract

Background Klotho is a protein known for its beneficial effects on longevity. Centcyamine is an alkaloid present in certain plants whose extracts have an anti‐inflammatory effect. Skin fibroblasts are essential to the formation and structure of the dermis. Objective Centcyamine is an indole‐based alkaloid composed of coumaric acid, a resveratrol precursor and methoxytryptamine, which can be both a precursor, or a derivative, of melatonin. Given these building blocks and their well‐known bioactivities, it was of interest to explore the potential benefits of using this aryl‐alkaloid, in cosmetic skincare applications. Methods We tested cultured normal human dermal fibroblasts (NHDF) in vitro to observe how supplementation with centcyamine improves properties of the cells to counteract the effect of ageing. The expression of genes and proteins of interest was quantified. The effect on doubling time and cell function was evaluated following treatment of the cells over several replication cycles. Skin firmness, red spot index and skin isotropy were measured with Dynaskin®, Visia® and Primos® equipment, respectively, and compared over two months in a vehicle‐controlled clinical trial on 60 persons. Results Centcyamine activates the expression of the gene KL and the related protein Klotho in dermal fibroblasts. Moreover, centcyamine slows the replicative ageing process of fibroblasts in culture. These cells retain cellular functions identical to those of young cells: the synthesis of lamin B1, a crucial regulatory protein of proliferation, as well as of collagen I and elastin is retained in aged cells. The clinical data are shown to improve skin isotropy in a majority of subjects, to reduce the red spot intensity and to maintain skin firmness in the treated group vs. the vehicle. Conclusion The alkaloid centcyamine induces changes in the metabolism of the ageing process of human dermal fibroblasts. The up‐to‐now unobserved implication of both Klotho and lamin B1 to maintain homeostasis of the skin opens new venues for the prevention of age‐related changes in skin structure. The in vitro and clinical data, while not demonstrated to be causally related, converge towards a common goal of skin repair and slower ageing processes.

Melatonin Exerts Prominent, Differential Epidermal and Dermal Anti-Aging Properties in Aged Human Eyelid Skin Ex Vivo

“…This shows that the multi-level anti-aging effects exerted by high-dose melatonin in human skin (Figures 1a-f, 2a-f, 3a,b and 4a-d) are by no means present across the board, and instead are more differential and selective than the very broad range of antiaging/senotherapeutic effects of melatonin reported in the cell culture and animal [86][87][88][89] had led us to expect.…”