ANTI-AGEING 131
New ingredient from Rosa rugosadelays skin ageing
n Annalisa Tito – Arterra Bioscience, Italy Claudia Zappelli, Maura Angelillo – Vitalab, Italy Maria Gabriella Colucci, Fabio Apone – Arterra Bioscience & Vitalab, Italy
Skin ageing is a very complex phenomenon caused by both intrinsic and extrinsic factors, and it is certainly the most relevant concern in cosmetics and dermatology. As cells age, the production and the organisation of the important components that constitute both the epidermis and the dermis matrixes decline, leaving visible signs on the surface of the skin. Although many of the mechanisms involved in the ageing process have not been completely clarified yet, a lot of research has been conducted so far and several factors responsible for the senescence progression and youth maintenance have been identified. Moreover, the activity of different plant derived compounds on cell ageing have been studied and their effects in slowing down or even partially revert the ageing phenotypes have been demonstrated.1
Indeed, several antioxidant
molecules, such as vitamins, flavonoids, phenolic acids and lignans, are capable of protecting skin cells against environmental insults and enhancing self-repair mechanisms during ageing, when topically applied in skin care creams.2 In the last years of research in skin ageing,
a pro-youth protein, called “Growth Differentiation factor 11” (GDF11), was identified as a circulating factor in human blood. GDF11 belongs to the Transforming Growth Factor beta (TGFβ) family, which includes other factors that modulate the growth and the differentiation of many cell types.3
family, GDF11 binds to specific transmembrane receptors, which, upon activation and phosphorylation of the transcription factor Smad2, trigger signal transduction pathways, leading to the regulation of target genes in the nucleus.4-5 GDF11 biological effects in promoting cell rejuvenation were demonstrated in tissues like heart, muscles or nervous system,6
Abstract
Skin ageing is an inevitable physiological process, determined by several concomitant factors, resulting in a thinner and drier skin, in the formation of fine wrinkles, and a gradual dermal atrophy. During this process the skin cells become senescent, they slow down their metabolism and the production of structural matrix components. The Growth Differentiation Factor 11 (GDF11) has been recently identified as a pro-youth factor in several cell types, and in particular it was shown its involvement in the restoration of a young phenotype in skin fibroblasts, by stimulating important Extra- Cellular Matrix proteins. Furthermore, its key role in modulating mitochondrial functions in skin cells during ageing has been highlighted. In the present article, we describe the characterisation of a plant extract, obtained from Rosa rugosa tissue cultures, able to produce a ‘rejuvenating’ effect in aged skin fibroblasts by inducing GDF11 expression and synthesis. The extract was also capable of increasing the expression of PGC1- alpha, the master regulator of the mitochondrial biogenesis, and other important genes involved in the pathway, leading to an improvement of cell metabolism and longevity.
factors involved in building up new mitochondria, including the Nuclear Respiratory Factors NRF1 and NRF2, and the Mitochondrial Transcription Factor A (TFAM).9
Increasing PGC-1α levels in the
skeletal muscle was sufficient to forestall the occurrence of age-related dysfunctions10 while a complete loss of the mitochondrial DNA (mtDNA) functionality caused the development of skin wrinkles, epidermal hyperplasia, inflammatory phenotype, and hair loss.11
Other important factors Similarly to the other members of the Graphical abstract. and
more recently we reported that it has got a very promising role in the skin as well, since it reverted senescent phenotypes in adult cells and restored the production of collagens and
April 2020
periostin to that of young fibroblasts.7 Other findings highlighted that GDF11 was involved in stimulating cell metabolism, in particular mitochondria functions by inducing the gene expression of the Peroxisome proliferator-activated receptor Gamma Coactivator 1 alpha (PGC1α)8 which is the master regulator of mitochondrial biogenesis. In turn PGC1α regulates the activity of several transcription
regulating metabolic homeostasis and ageing progression, even under stress conditions, are the Sirtuins (Sirt), a family of seven mammalian nicotinamide adenine dinucleotide (NAD+)-dependent enzymes.12 Among them, Sirt1 and Sirt6 are responsible for cell longevity and take part in DNA repair mechanisms13
while Sirt3 and
Sirt4 are expressed in the mitochondria and have been linked to a correct mitochondrial metabolic activity.14 In a screening to identify new compounds with rejuvenating activity through the activation of GDF11 and Sirtuins, we found that a hydrosoluble extract derived from Rosa rugosa tissue cultures was particularly effective on skin fibroblasts. Extracts derived from plant tissue cultures have been more and more
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