title: Modulation of cellular senescence in fibroblasts and dermal papillae cells in vitro.
abstract: A hexapeptide (Hexapeptide-11) of structure Phe-Val-Ala-Pro-Phe-Pro (FVAPFP) originally isolated from yeast extracts and later synthesized by solid state synthesis to high purity has demonstrated an ability to influence the onset of senescence in intrinsically aged fibroblasts, extrinsically aged fibroblasts, and extrinsically aged dermal papillae cells in vitro. The mechanism of senescence control is believed to be related to the peptide's ability to reversibly downregulate ataxia telangiectasia mutated (ATM) and p53 protein expression. The importance of p53 as the gatekeeping protein for monitoring cellular DNA damage is strategic for maintaining cellular health. ATM activates p53 by direct phosphorylation, causing cells to move into senescence which effectively moves them out of reproductive processes. Technologies that can influence ATM and p53 expression may offer unique benefits for controlling cellular senescence and effectively delaying cellular aging processes. The influence on ATM and p53 expression is noted to occur in both cell lines at peptide concentrations between 0.1% and 1.0%. The implications of these effects for aging benefits for skin and hair is important as, to date, no known small peptide has been suggested to demonstrate this effect in such a reversible and dose-dependent fashion.
authors.affiliation: Arch Personal Care, South Plainfield, NJ 07080, USA. vince.gruber@lonza.com
authors.forename: James V
authors.initials: JV
authors.lastname: Gruber
authors.forename: Philip
authors.initials: P
authors.lastname: Ludwig
authors.forename: Robert
authors.initials: R
authors.lastname: Holtz
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D001685:Biological Factors / Q000138:chemical synthesis / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005656:Fungal Proteins / Q000138:chemical synthesis / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010766:Phosphorylation; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D060327:Solid-Phase Synthesis Techniques; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D001685:Biological Factors; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009842:Oligopeptides; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C581722:Phe-Val-Ala-Pro-Phe-Pro