IVA DOLEČKOVÁ*, MARKÉTA MAREŠOVÁ, ROMANA ŠULÁKOVÁ, ROMAN FRYČÁK, TOMÁŠ MUTHNÝ
*Corresponding author
Contipro a.s., Dolní Dobrouč, Czech Republic

Abstract

Klotho is an anti-ageing protein which promotes body´s health, prolongs lifespan and its level decreases with age. Klotho-deficiency leads to dry, rough, wrinkled and less elastic skin with pigmentation disorders. For this reason, klotho emerged as an interesting target to combat the typical signs of the ageing skin. 

In this study, we used a short peptide fragment of klotho and tested it both in vitro and in vivo. The klotho fragment inhibited the same signalling pathway as the original protein leading to activation of the defensive mechanisms protecting organism from oxidative stress, the major cause of ageing. The in vivo study on human volunteers showed multiple beneficial effects including highly significant wrinkle reduction and the skin inner structure improvement.

INTRODUCTION

Structure and function of klotho 

In ancient Greek mythology, Clotho was a goddess who determined the length of life and destiny of every mortal from birth to death. The klotho gene got its name due to its similar connection to the life span of various organisms. Klotho is expressed in various types of tissue, mainly in kidney and brain (3, 4). It is produced in two isoforms. The first one is a transmembrane protein whereas the second one is released to the blood stream or cerebrospinal fluid and circulates in human body (5-7). The two isoforms also differ in their function. The membrane bound klotho plays a role in vitamin D-dependent phosphate and calcium homeostasis (8, 9) whereas the circulating form functions as a systemic humoral factor possessing anti-ageing and organ-protecting effects by various types of mechanisms. It plays a role in maintaining ion homeostasis by regulating ion channels and transporters and modulates cellular signalling by suppressing activation of insulin receptor (IR), insulin growth factor receptor (IGFR) (10) and Wnt signalling pathways (11). The inhibition of insulin signalling promotes express ...