The Role of the Kynurenine Pathway in the Pathophysiology of Frailty, Sarcopenia, and Osteoporosis

Tryptophan is an essential nutrient required to generate vitamin B3 (niacin), which is mainly involved in energy metabolism and DNA production. Alterations in tryptophan metabolism could have significant effects on aging and musculoskeletal health. The kynurenine pathway, essential in tryptophan catabolism, is modulated by inflammatory factors that are increased in older persons, a process known as inflammaging. Osteoporosis, sarcopenia, osteosarcopenia, and frailty have also been linked with chronically increased levels of inflammatory factors. Due to the disruption of the kynurenine pathway by chronic inflammation and/or changes in the gut microbiota, serum levels of toxic metabolites are increased and are associated with the pathophysiology of those conditions. In contrast, anabolic products of this pathway, such as picolinic acid, have demonstrated a positive effect on skeletal muscle and bone. In addition, physical activity can modulate this pathway by promoting the secretion of anabolic kynurenines. According to the evidence collected, kynurenines could have a promising role as biomarkers for osteoporosis sarcopenia, osteosarcopenia, and frailty in older persons. In addition, some of these metabolites could become important targets for developing new pharmacological treatments for these conditions.