Identification of Salvia haenkei as 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 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-ɑ 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.

Machine learning for predicting lifespan-extending chemical compounds

“…In this work we analyse data from the DrugAge database [ 10 ], which contains information about chemical compounds and their effect on the lifespan of organisms. DrugAge contains a variety of compounds with anti-ageing properties such as gerosuppressant, geroprotective and senolytic activity [ 11 – 13 ] as well lifespan increasing properties for a specific species. Existing databases with lifespan-extending drugs include AgeFactDB ( http://agefactdb.jenage.de/ ) [ 14 ], and Geroprotectors.org [ 15 ] ( http://geroprotectors.org/ ).…”

Further assessment of Salvia haenkei as an innovative strategy to counteract skin photo-aging and restore the barrier integrity

“…Cellular senescence is defined as a stable arrest of cell growth that occurs in all human cells during aging [ 15 – 17 ]. As a result of stressful events, such as oncogene over-expression, ROS generation and DNA damage (for example induced by UVR, in particular by UVB light), cells may prematurely become senescent [ 18 ]. In this scenario, it appears evident the importance of developing innovative strategies able to prevent the accumulation of senescent cells or to selectively kill them, thus counteracting aging and aging-associated disorders.…”

“…In this scenario, it appears evident the importance of developing innovative strategies able to prevent the accumulation of senescent cells or to selectively kill them, thus counteracting aging and aging-associated disorders. Recently, we identified Salvia haenkei (SH), a Bolivian plant rich in vitamin B and antioxidant properties, as a potential anti-senescence agent [ 18 ].…”

“…In fact, despite senescent cells are unable to proliferate, they possess high metabolic activity and they efficiently produce several pro-inflammatory molecules [ 19 ]. By using a model of skin human epidermis (EpiSkin), it was indeed demonstrated that SH extract decreases the levels of senescent cells by affecting the IL1ɑ release and reducing ROS generation [ 18 ].…”

<p>Evaluation of Wound Healing Activity of <em>Salvia haenkei</em> Hydroalcoholic Aerial Part Extract on in vitro and in vivo Experimental Models</p>

“…Recently, a new medical use was attributed to Salvia haenkei , thanks to the research of Alimonti et al, that demonstrated an antisenescence activity of Salvia haenkei , suggesting a potential use of Salvia haenkei based products for antiaging skin treatments. 9 , 10 …”