Water-soluble tomato concentrate: Identified as a novel natural product to ameliorate age-related loss of muscle mass and function in a Sirt3-dependent manner.

Exercise is well-established to alleviate the debilitating age-related muscle decline, while through poorly defined mechanisms, raising concerns about identified exercise mimetics based on the " one target " paradigm. This research seeks to find a novel natural product that mimics the effects of exercise on aging skeletal muscle. Here, using an in silico transcriptome-based screening strategy, we discovered a standard water-soluble tomato concentrate (Wstc) as a top-ranked candidate for improving age-related muscle wasting. We found that Wstc efficiently inhibited muscle atrophy in senescent C2C12 myotubes. Treatment with Wstc in aged mice reduced the activity of aging biomarkers, inflammatory mediators, and oxidative stress in their serum and skeletal muscle. Furthermore, Wstc also protected against age-induced muscle decline by markedly increasing muscle mass and physical performance in aged mice. Mechanistically, Wstc activated the AMPK/FOXO3/Sirt3 axis. Ablation of Sirt3 significantly attenuated the Wstc-mediated suppression of aging-induced muscle atrophy both in vitro and in vivo.