Pairwise combinations of chemical compounds that delay yeast chronological aging through different signaling pathways display synergistic effects on the extent of aging delay

// Pamela Dakik 1 , Mélissa McAuley 1 , Marisa Chancharoen 1 , Darya Mitrofanova 1 , Monica Enith Lozano Rodriguez 1 , Jennifer Anne Baratang Junio 1 , Vicky Lutchman 1 , Berly Cortes 1 , Éric Simard 2 and Vladimir I. Titorenko 1 1 Department of Biology, Concordia University, Montreal, Quebec, Canada 2 Idunn Technologies Inc., Rosemere, Quebec, Canada Correspondence to: Vladimir I. Titorenko, email: [email protected] Keywords: yeast; cellular aging; geroprotectors; cellular signaling; gerotarget Received: November 15, 2018 Accepted: December 20, 2018 Published: January 08, 2019 ABSTRACT We have recently discovered six plant extracts that delay yeast chronological aging. Most of them affect different nodes, edges and modules of an evolutionarily conserved network of longevity regulation that integrates certain signaling pathways and protein kinases; this network is also under control of such aging-delaying chemical compounds as spermidine and resveratrol. We have previously shown that, if a strain carrying an aging-delaying single-gene mutation affecting a certain node, edge or module of the network is exposed to some of the six plant extracts, the mutation and the plant extract enhance aging-delaying efficiencies of each other so that their combination has a synergistic effect on the extent of aging delay. We therefore hypothesized that a pairwise combination of two aging-delaying plant extracts or a combination of one of these plant extracts and spermidine or resveratrol may have a synergistic effect on the extent of aging delay only if each component of this combination targets a different element of the network. To test our hypothesis, we assessed longevity-extending efficiencies of all possible pairwise combinations of the six plant extracts or of one of them and spermidine or resveratrol in chronologically aging yeast. In support of our hypothesis, we show that only pairwise combinations of naturally-occurring chemical compounds that slow aging through different nodes, edges and modules of the network delay aging in a synergistic manner.