Studying a gut hormone called FGF-19 in older adults with and without frailty

Fibroblast Growth Factor 19 (FGF-19) is an intestinal hormone secreted in the post-prandial state, whose primary role is to inhibit bile acid synthesis in the liver. It is expressed by the FXR (Farnesoid X receptor) nuclear receptor in the enterocytes of the ileum, which is activated by specific bile acids metabolized in the gut microbiota. It was demonstrated that treatment with FGF-19 induces myofiber hypertrophy in vitro and increases muscle strength and mass in mice model of sarcopenia. Sarcopenia and the commonly associated physical frailty, are age-related syndromes associated with adverse events (such as falls and fractures, mobility disability) and increased mortality. Currently, there is no drug treatment that has been proven effective to counteract those syndromes and standard care consists in non-pharmacological interventions (exercise and nutrition) whose implementation remains complex due to several barriers. Moreover, the anabolic resistance underlying sarcopenia hampers the exercise-induced response on muscle mass and the level of evidence for this outcome remains poor-to-moderate. Thus, FGF-19 could be considered as a new regulator of skeletal muscle in elderly living with sarcopenia/frailty but there are, to date, only few data available in the literature. First and foremost, it is crucial to understand the relationship between postprandial FGF-19 and muscle which has not been characterized yet. Preliminary data suggest an inverse relationship between FGF-19 and physical function (OR= 0.33 [0.15;0.7] for the highest tertile of FGF-19) that persisted only in the cluster of frail individuals (OR= 0.19 [0.05;0.65]. Mechanistically, this suggests a positive feedback loop of the bile acids-gut-microbiota-FGF-19 in the presence of frailty/sarcopenia hence indicating that FGF-19 may be a novel biomarker of this condition.