GDF-15

•Observational— Powerful prognostic marker; therapeutic targets early

What it is

GDF-15 (growth/differentiation factor 15, also called MIC-1) is a divergent TGF-β superfamily member secreted under cellular stress — mitochondrial dysfunction, hypoxia, oxidative stress, tissue injury. It acts through the brain receptor GFRAL to suppress appetite (the mechanism behind cachexia in cancer and metformin-induced weight loss).

Why it matters

• Strongest single-protein predictor of all-cause mortality in older adults across multiple cohorts.
• Mitochondrial disease biomarker (rises early in mitochondrial myopathy).
• Marker of metformin response.
• Rises in heart failure, CKD, and many cancers.

Therapeutic targeting

GFRAL antagonists are in development for cancer cachexia (reverse the appetite suppression). Conversely, GDF-15 agonists are being explored for obesity (mimicking the cachexia signal). NGM Biopharmaceuticals and others have programmes.

Limitations

• Non-specific: rises in many conditions.
• Not yet in standard panels; usually requires research-style ordering.
• Reference ranges age-dependent.

Related entries

Mitochondrial dysfunction, Frailty, Metformin, Heart failure.