The Growth Differentiation Factor 11 is Involved in Skin Fibroblast Ageing and is Induced by a Preparation of Peptides and Sugars Derived from Plant Cell Cultures

Ageing is a complex and progressive phenomenon, during which the accumulation of morphological and chemical changes seriously compromises the capacity of the cells to proliferate and fulfil their biological tasks. The increase in the average age of the world population, associated with a higher occurrence of age-related diseases, is prompting scientific research to look for new strategies and molecular targets that may help in alleviating age-related phenotypes. Growth factors, responsible for modulating several aging markers in many tissues and organs, represent valuable targets to fight age-associated dysfunctions. The growth differentiation factor GDF11, a TGF-β family member, has been associated with the maintenance of youth phenotypes in different human tissues and organs, and in the skin has been related to an inhibition of the inflammatory response. We investigated the role of GDF11 in skin dermal fibroblasts, and we observed that its expression and activity were reduced in fibroblasts deriving from adult donors compared to neonatal ones. The main effect of GDF11 was the induction of collagen I and III, in both neonatal and adult fibroblasts, by triggering Smad signalling in a TGF-β-like fashion. Moreover, by analysing a number of plant extracts having GDF11 inducing activity, we found that a peptide/sugar preparation, obtained from Lotus japonicus somatic embryo cultures, was capable of restoring GDF11 expression in older fibroblasts and to activate the synthesis of collagen I, collagen III and periostin, an important protein involved in collagen assembly. [Figure not available: see fulltext.].