Withania somnifera (Ashwagandha) Improves Fitness in Aged Drosophila by Reducing AKT Phosphorylation.

With increasing global life expectancy, there is a growing need for strategies to mitigate age-related declines in fitness and health. Withania somnifera (WS), commonly known as ashwagandha, has been traditionally recognized by ayurvedic medicine for its benefits in promoting healthy aging. More recently, it has also emerged as a potential treatment option for age-related diseases such as Alzheimer's disease (AD), Parkison's disease, and Huntington's disease. WS has been shown to improve sleep quality, has adaptogenic and antioxidant properties, and enhances exercise performance by improving muscle strength and recovery. However, the molecular mechanisms underlying the effects of WS on aging are poorly understood. Therefore, we used Drosophila melanogaster flies to assess the impact of analytically characterized water (WSAq) extracts of WS root. To test effects during aging, the flies were treated at middle-age (4 weeks from eclosion) for two weeks. We found that WSAq reduced Akt phosphorylation in fly heads and that Akt is required to improve fitness in the fast phototaxis assays. We also determined that the effects of WSAq treatment depended on the Akt downstream pathways Tsc/mTOR, FOXO, and NRF. This supports that WS provides resilience to the age-related decline in fitness by modifying Akt signaling and affecting downstream pathways connected to aging and longevity.