GDF15 (Growth Differentiation Factor 15)
DEGDF15 (Wachstumsdifferenzierungsfaktor 15)
GDF15 (growth differentiation factor 15), also called MIC-1, is an unusual member of the TGF-β protein family. Normally it sits at low levels. But it shoots up under mitochondrial stress, DNA damage, inflammation, and many other cellular stresses. It works through a dedicated receptor pair, GFRAL and RET, in your hindbrain, where it curbs appetite and lowers body weight. That matters for cancer wasting (cachexia), and for drugs like metformin, which sharply raises GDF15. Circulating GDF15 climbs with age. It is tied to markers of frailty, heart disease, and all-cause death. It is increasingly studied as a readout of mitochondrial stress and biological age. But its net role, harmful stress signal or helpful adaptation, depends heavily on context.
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Sources
- Liu H, Huang Y, Lyu Y, Dai W, Tong Y, Li Y. (2021). GDF15 as a biomarker of ageing. *Experimental Gerontology*doi:10.1016/j.exger.2021.111228
- Mullican SE, Lin-Schmidt X, Chin CN, Chavez JA, Furman JL, Armstrong AA, Beck SC, et al.. (2017). GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates. *Nature Medicine*doi:10.1038/nm.4392