{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:54:15Z","timestamp":1790916855864,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["U19AT010829"],"award-info":[{"award-number":["U19AT010829"]}]},{"award":["U19AT010829"],"award-info":[{"award-number":["U19AT010829"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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\u2019s disease (AD), Parkison\u2019s disease, and Huntington\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms27188314","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:18:26Z","timestamp":1790860706000},"page":"8314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Withania somnifera (Ashwagandha) Improves Fitness in Aged Drosophila by Reducing AKT Phosphorylation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0954-7147","authenticated-orcid":false,"given":"Alexander D.","family":"Law","sequence":"first","affiliation":[{"name":"BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0892-1608","authenticated-orcid":false,"given":"Mikah","family":"Brandes","sequence":"additional","affiliation":[{"name":"BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Bollen","sequence":"additional","affiliation":[{"name":"BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1569-6453","authenticated-orcid":false,"given":"Amala","family":"Soumyanath","sequence":"additional","affiliation":[{"name":"BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Kretzschmar","sequence":"additional","affiliation":[{"name":"BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","first-page":"453","article-title":"As lifespan increases, people spend more years burdened by disease","volume":"333","author":"Orrall","year":"2025","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pandey, S., Pant, P., Corbioli, G., Bonazzi, E., Cisneros-Yupanqui, M., Salmaso, P., and Dall\u2019Acqua, S. 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