GDF15 (Growth Differentiation Factor 15)

GDF15 (growth differentiation factor 15), also known as MIC-1, is a divergent TGF-β superfamily member that is expressed at low levels under homeostatic conditions but is strongly induced by mitochondrial stress, DNA damage, inflammation, and diverse cellular stressors. It signals through a dedicated receptor complex comprising GFRAL and RET in the hindbrain to suppress appetite and reduce body weight, a mechanism relevant to cancer cachexia and the metabolic effects of drugs such as metformin, which robustly elevates GDF15. Circulating GDF15 rises with age and is associated with markers of frailty, cardiovascular disease, and all-cause mortality; it is increasingly studied as a biomarker of mitochondrial stress and biological age, though its net role — detrimental stress signal or adaptive mediator — depends heavily on context.