Anti-Aging Effects of Ketanserin; Ketanserin Extends Lifespan in Female Drosophila, Inhibits Cellular Senescence and Promotes Wound Healing In-vitro

Abstract

Aims: The lifespan of an organism depends on intertwined mechanisms, difficult to fully unravel. 5-HT (serotonin) receptors are known to be involved in aging process and wound healing which is significantly slowed down through aging. The present research aims to unravel if Ketanserin, an inhibitor of 5-HT2 receptors, exerts anti-aging effects. Study Design: Skin fibroblasts were chosen to study the effects of ketanserin on senescence and wound healing. Drosophila flies were chosen to study the effect of ketanserin on lifespan. Place and Duration of Study: UMCG and TUMS, pharmacy department, one year. Methodology: Skin fibroblasts were treated with Ketanserin and subjected to oxidative stress. To evaluate the potential of Ketanserin in preventing cellular damage and senescence, cell survival, ROS (reactive oxygen species) formation, Caspase 3/7, beta-galactosidase and thiol group contents were measured. Further, mTOR (mammalian target of rapamycin) pathway components were studied in treated and control cells using western blotting techniques. Scratch assay was also performed on fibroblast cell cultures. To evaluate the longevity promoting effects of Ketanserin, Drosophila were treated with Ketanserin and studied. Results: Ketanserin increased Drosophila lifespan by 35% without inhibiting the overall growth. It inhibited mTOR and upregulated autophagy in skin fibroblasts and prevented H2O2 induced senescence. Ketanserin was found to promote wound closure in-vitro, probably through inhibition of cellular retraction and the increase in viable cell number. Further, Ketanserin inhibited ROS production and Caspase activity while increasing free thiol group levels in both Drosophila larvae and fibroblast cells subjected to oxidative stress. Conclusion: Ketanserin shows to exert anti-aging effects in both cells and Drosophila. Further it has a positive effect on the wound healing process which is impaired in aging organisms. This is the first report showing that Ketanserin increases lifespan in an organism, although the exact mechanism remains to be still explored.