title: Identification ofSalvia haenkeias gerosuppressant agent by using an integrated senescence-screening assay.
abstract: Cellular senescence is a stable cell cycle arrest that is the causative process of aging. The PI3K/AKT/mTOR pathway is implicated in the control of cellular senescence and inhibitors of this pathway have been successfully used for life span prolongation experiments in mammals. PTEN is the major regulator of the PI3K/AKT/mTOR pathway and loss of PTEN promotes a senescence response termed PICS. Here we report a novel-screening assay, for the identification of compounds that block different types of senescence response. By testing a library of more than 3000 natural and chemical compounds in PTEN deficient cells we have found that an extract fromSalvia haenkei(SH), a native plant of Bolivia is a potent inhibitor of PICS. SH also decreases replicative and UV-mediated senescence in human primary fibroblasts and in a model ofin vitroreconstructed human epidermis. Mechanistically, SH treatment affects senescence driven by UV by interfering with IL1-α signalling. Pre-clinical and clinical testing of this extract by performing toxicity and irritability evaluationin vitroalso demonstrate the safety of SH extract for clinical use as anti-aging skin treatment.
authors.affiliation: Laboratory for Research and Development in Aging, Atrahasis S.r.l., 00189 Rome, Italy.|Research Center, San Pietro "Fatebenefratelli", 00189 Rome, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Matic
authors.affiliation: Institute of Oncology Research (IOR), Bellinzona CH 6500, Switzerland.
authors.forename: Ajinkya
authors.initials: A
authors.lastname: Revandkar
authors.affiliation: Institute of Oncology Research (IOR), Bellinzona CH 6500, Switzerland.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Chemistry and Pharmaceutical Technologies, University of Genova, 16126 Genova, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Bisio
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35121 Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Dall'Acqua
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35121 Padova, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Cocetta
authors.affiliation: Department of Molecular Medicine, University of Padova, 35121 Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.affiliation: Research Center, San Pietro "Fatebenefratelli", 00189 Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Mancino
authors.affiliation: Studio Associato Gaia Snc, 16121 Genova, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Milanese
authors.affiliation: Animal Technology Facility of University Tor Vergata, 00173 Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mattei
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35121 Padova, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Montopoli
authors.affiliation: Laboratory for Research and Development in Aging, Atrahasis S.r.l., 00189 Rome, Italy.|Institute of Oncology Research (IOR), Bellinzona CH 6500, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Alimonti
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000528:radiation effects; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D027544:Salvia / Q000737:chemistry*
chemical_list: D053582:Interleukin-1alpha; D010936:Plant Extracts; D006861:Hydrogen Peroxide
keywords: PICS; Salvia haenkei; gerosuppressant; senescence; senescence-screening assay