Research Paper Volume 8, Issue 12 pp 3223—3240
Identification of Salvia haenkei as gerosuppressant agent by using an integrated senescence-screening assay
- 1 Laboratory for Research and Development in Aging, Atrahasis S.r.l., 00189 Rome, Italy
- 2 Department of Chemistry and Pharmaceutical Technologies, University of Genova, 16126 Genova, Italy
- 3 Research Center, San Pietro “Fatebenefratelli”, 00189 Rome, Italy
- 4 Animal Technology Facility of University Tor Vergata, 00173 Rome, Italy
- 5 Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35121 Padova, Italy
- 6 Department of Molecular Medicine, University of Padova, 35121 Padova, Italy
- 7 Studio Associato Gaia Snc, 16121 Genova, Italy
- 8 Institute of Oncology Research (IOR), Bellinzona CH 6500, Switzerland
Received: August 1, 2016 Accepted: November 14, 2016 Published: December 1, 2016
https://doi.org/10.18632/aging.101076How to Cite
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 from Salvia 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 of in vitro reconstructed 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 evaluation in vitro also demonstrate the safety of SH extract for clinical use as anti-aging skin treatment.