FGF21 (Fibroblast Growth Factor 21)

FGF21 (fibroblast growth factor 21) is an endocrine member of the FGF superfamily secreted primarily by the liver in response to fasting, dietary protein restriction, and mitochondrial stress, acting on target tissues through FGFR1c/β-Klotho co-receptor complexes. It promotes fatty acid oxidation, ketogenesis, and insulin sensitisation, and suppresses growth hormone/IGF-1 axis activity. Transgenic mice overexpressing FGF21 live roughly 30–40% longer with improvements in metabolic health and adiposity, while elevated circulating FGF21 in humans is paradoxically associated with metabolic disease and frailty, likely reflecting compensatory induction in states of metabolic stress rather than a direct pro-ageing role. Pharmacological FGF21 analogues are in clinical development for metabolic liver disease.