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Effective therapeutic strategies remain limited. Here we report UA-30, a novel compound with a favorable pharmacokinetic and safety profile, that delayed systemic aging in naturally aged mice, as indicated by reduced frailty, slowed epigenetic age, extended lifespan, and improved muscle function. 10-wk UA-30 treatment reduced fibrosis and muscle atrophy in 18.5-mo-old mice. Thermal proteome profiling, surface plasmon resonance, and functional analyses identified Ras-related protein Ral-A (RalA) as a direct molecular target of UA-30. UA-30 suppressed RalA activity, thereby inhibiting the pro-fibrotic JNK\u2013Smad signaling axis and enhancing mitochondrial functions. Overexpression of constitutively active RalA largely abolished the anti-aging and anti-fibrotic effects of UA-30. These findings support UA-30 as a promising therapeutic candidate for aging and sarcopenia, and indicate RalA is a potential target for age-related muscle degeneration.<\/jats:p>","DOI":"10.1084\/jem.20260071","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T06:20:49Z","timestamp":1785910849000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["UA-30 mitigates systemic aging and motor decline by inhibiting RalA signaling in naturally aged mice"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7528-3101","authenticated-orcid":true,"given":"Bingge","family":"Zhang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00p991c53","id-type":"ROR","asserted-by":"publisher"}],"name":"Tongji Medical College, Huazhong University of Science and Technology 1 Key Laboratory of Ministry of Education of China and Hubei Province for 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