Biomarker

GDF-15

Last updated 2026-05-30· 1 min read· Evidence: observational

Reviewed by the Ultimate Longevity Bible editorial team. Educational reference — not medical advice. See disclaimer.

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.

References

Wischhusen, J. et al. Growth/differentiation factor-15 (GDF-15): from biomarker to novel targetable immune checkpoint. Front. Immunol. 11, 951 (2020).