The youth protein klotho: new target for anti-ageing

On the other hand, when it is overexpressed, this gene leads to a 20% to 30% increase in mice lifespan. The skin of klotho-deficient mice is thin and atrophic. Histological examination shows reduced number of hair follicles and reduced thickness of the dermal and epidermal layers.2

The klotho protein is available in two forms: the transmenbrane form and the secreted form2 which have distinct functions but can collectively affect ageing processes. Secreted klotho is involved in a large number of signalling pathways leading to the re-establishment of optimal cellular function, among them it has been suggested that klotho may inhibit the insulin/IGF-1 signalling pathway3 (Fig. 2) and thus participate in the suppression of oxidative stress via Forkhead box (FOXO). FOXOs up-regulate expression of multiple genes, including antioxidant enzymes such as catalase.4 These FOXO are negatively regulated by insulin/IGF-1 signalling. Indeed, activation of insulin/IGF-1 signalling increases activity of a serine-threonine kinase Akt, which in turn phosphorylates FOXOs. Phosphorylated FOXOs are excluded from the nucleus and are unable to function as transcription factors. By inhibiting the insulin/IGF-1 signalling pathway, klotho down-regulate AKT and promote the predominance of the unphosporylated FOXOs.5

Codif International laboratories have demonstrated a direct link between klotho expression and fibroblast ageing (Fig. 3). The decrease in klotho expression starts very early during the ageing process: from roughly 30 years. Then its expression gradually decreases with fibroblast ageing. Increasing klotho synthesis in the fibroblasts thus represents a new strategy to combat skin ageing.