This talk will highlight the emerging role of gut microbiota-derived metabolites (GMDMs) as pivotal regulators of host physiology and aging. Urolithin A (UA), a first-in-class mitophagy activator derived from microbial metabolism of ellagitannins, has demonstrated significant efficacy in enhancing muscle function, as shown in Nature Medicine (2016) and Nature Metabolism (2019), and was further validated in two independent double-blind, placebo-controlled trials published in JAMA Network Open (adults aged 65–90 years) and Cell Reports Medicine (mean age ~52 years, BMI ~29) in 2022. Building on UA’s translational success, we recently identified additional GMDMs with longevity-promoting potential.
In the latter part of this talk, I will present our recent findings published in Nature Communications (2024), which revealed that 3-phenyllactic acid (PLA), a microbial metabolite secreted by Lactiplantibacillus plantarum, extends healthspan in Caenorhabditis elegans by activating energy metabolism and stress resilience pathways in a SKN-1/ATFS-1-dependent manner. Notably, circulating PLA levels inversely correlate with physical performance in individuals with sarcopenia. To assess its translational relevance, we established a composite Healthy Aging Index (HAI) integrating motility, mitochondrial respiration, and ATP levels. These findings support the therapeutic potential of selected GMDMs in mitigating age-related muscle decline and enhancing metabolic resilience in aging populations.