Picolinic acid, a tryptophan metabolite, exhibits anabolic effects in muscle cells and improves lifespan and movement in <i>C. elegans</i>

Compounds promoting anabolic effects on muscle and bone may offer an ideal treatment for osteosarcopenia while potentially impacting healthspan and lifespan. We previously demonstrated the anabolic effects of picolinic acid (PIC), a tryptophan metabolite, on bone both in vitro and in vivo. However, its effects on muscle and potential additional effects on lifespan and healthspan are not yet fully understood. This study aimed to investigate PIC's effects on muscle cells in vitro and its impact on mobility and lifespan in an animal model. Murine C2C12 and human myoblasts were treated with PIC (1, 50, and 100 µM) or vehicle for 5 days. Myogenic regulatory factors (MRFs) were evaluated, and the fusion index and myotubules' length were calculated at timed intervals (day 1, 3, and 5). In vivo, Caenorhabditis elegans were treated with increasing doses of PIC, and their lifespan and rate of movement (thrashing) were evaluated at timed intervals. PIC-treated myoblasts showed a higher and earlier expression of MRFs. On day 3, PIC-treated myotubes were significantly more fused and longer when treated with PIC than vehicle-treated controls. C. elegans treated with 1 mM of PIC showed a significantly longer lifespan. In addition, the mobility of PIC-treated C. elegans was significantly increased at all timed points. In conclusion, this study demonstrates that, besides its anabolic effect on bone, PIC has an anabolic effect on muscle, which is also associated with a longer lifespan in PIC-treated C. elegans. This evidence opens up promising avenues for further exploration of PIC as a novel therapy for osteosarcopenia with additional effects on healthspan and lifespan.