Abstract

As skin ages, impaired extracellular matrix (ECM) protein synthesis and increased action of degradative enzymes manifest as atrophy, wrinkling and laxity. There is mounting evidence for the functional role of exogenous peptides across many areas, including in offsetting the effects of cutaneous ageing. Here, using an artificial intelligence (AI) approach, we identified peptide RTE62G (pep_RTE62G), a naturally occurring, unmodified peptide with ECM stimulatory properties. The AI-predicted anti-ageing properties of pep_RTE62G were then validated through in vitro, ex vivo and proof of concept clinical testing. A deep learning approach was applied to unlock pep_RTE62G from a plant source, Pisum sativum (pea). Cell culture assays of human dermal fibroblasts (HDFs) and keratinocytes (HaCaTs) were subsequently used to evaluate the in vitro effect of pep_RTE62G. Distinct activities such as cell proliferation and ECM protein production properties were determined by ELISA assays. Cell migration was assessed using a wound healing assay, while ECM protein synthesis and gene expression were analysed, respectively, by immunofluorescence microscopy and PCR. Immunohistochemistry of human skin explants was employed to further investigate the induction of ECM proteins by pep_RTE62G ex vivo. Finally, the clinical effect of pep_RTE626 was evaluated in a proof of concept 28-day pilot study. In vitro testing confirmed that pep_RTE62G is an effective multi-functional anti-ageing ingredient. In HaCaTs, pep_RTE62G treatment significantly increases both cellular proliferation and migration. Similarly, in HDFs, pep_RTE62G consistently induced the neosynthesis of ECM protein elastin and collagen, effects that are upheld in human skin explants. Lastly, in our proof of concept clinical study, application of pep_RTE626 over 28days demonstrated anti-wrinkle and collagen stimulatory potential. pep_RTE62G represents a natural, unmodified peptide with AI-predicted and experimentally validated anti-ageing properties. Our results affirm the utility of AI in the discovery of novel, functional topical ingredients.

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