Peucedanum japonicum Thunb. ameliorates age-related muscle loss by improving mitochondrial function in aged mice

Peucedanum japonicum Thunb. (PJ), also known as costal hog fennel, is an edible medicinal plant recognized for its potential health benefits. We previously demonstrated the protective effects of PJ against muscle atrophy in young mice. In the present study, we investigated whether PJ also inhibits age-related muscle loss in aged mice. PJ treatment of primary myoblasts derived from aged mice attenuated myotube diameter reduction, suppressed the expression of atrogenes, and prevented the fast-to-slow myosin heavy chain (MHC) fiber type transition. Additionally, PJ improved mitochondrial respiratory capacity, accompanied by increased PGC1α expression and phosphorylation. Aged mice (20 months old) were fed diets supplemented with 0.1% or 0.2% PJ for eight weeks. PJ supplementation enhanced muscle strength and physicalrformance parameters, including treadmill endurance and stride length. Increases in lean body mass, muscle weight, cross-sectional area (CSA), and the ratio of MHCII to MHCI fibers were observed. These improvements were associated with reduced ubiquitin-dependent protein degradation and the downregulation of atrogenes. Furthermore, PJ supplementation promoted mitochondrial activity via PGC1α and stimulated mitochondrial biogenesis through the Nrf1-Tfam pathway. 4-Caffeoylquinic acid (4-CQA), a major bioactive compound in PJ, attenuated myotube atrophy and enhanced mitochondrial respiration in aged myoblasts. These findings suggested that PJ, along with its active compound 4-CQA, has therapeutic potential for combating age-related muscle loss.