Taurine Fights Liver Aging by Boosting Hydrogen Sulfide and Silencing IGFBP-1

Cellular senescence — the permanent arrest of cell division without cell death — accumulates in chronically injured liver tissue and drives fibrosis, inflammation, and systemic organ dysfunction through secreted factors. Understanding how nutritional compounds can blunt this process is a key frontier in liver disease and longevity research.

This study employed a well-validated mouse model of chronic hepatotoxicity using carbon tetrachloride (CCl4) administered over 8 weeks, with oral taurine supplementation (3% in drinking water) introduced at week 4. The dual-phase design allowed assessment of taurine's therapeutic, not merely prophylactic, capacity. Endpoints included serum liver enzymes (AST, ALT), hepatic malondialdehyde (MDA) as a lipid peroxidation marker, immunostaining for senescence markers p21 and p16, and metabolic profiling of cysteine pathway intermediates including H₂S, cystine, and glutathione (GSH).

Taurine administration reversed CCl4-induced body weight loss, reduced serum AST and ALT, and lowered hepatic MDA. Critically, CCl4 treatment depleted hepatic taurine by ~38%, and supplementation restored these levels. Immunostaining confirmed that p21-positive senescent cells were significantly elevated by CCl4 and reduced by taurine; p16-positive cells were less abundant and unaffected by taurine. Re-analysis of prior transcriptomic data from taurine-treated normal mice revealed upregulation of CTH (cystathionine γ-lyase, the primary H₂S-producing enzyme) and downregulation of CSAD (which diverts cysteine toward taurine synthesis). In normal mice, taurine treatment increased hepatic CTH protein, elevated H₂S, and raised cystine, consistent with a metabolic shift redirecting cysteine flux from taurine biosynthesis toward H₂S production. Pharmacological inhibition of CTH with propargylglycine (PPG) partially reversed taurine's MDA-lowering effect and blunted AST/ALT normalization in 2 of 4 mice, implicating H₂S as a mechanistic mediator. Interestingly, H₂S elevation by taurine was not detectable in CCl4-injured livers, likely because excess reactive oxygen species rapidly consumed the H₂S produced.

A second major finding concerned hepatokine signaling. Transcriptomic reanalysis identified IGFBP-1 — insulin-like growth factor binding protein-1, a liver-secreted protein — as significantly downregulated by taurine in healthy mice. In the CCl4 model, IGFBP-1 was strongly induced, and taurine administration blocked this induction. IGFBP-1 has emerging roles in senescence-associated secretory phenotype (SASP) regulation and systemic IGF signaling. TGF-β1 was induced by CCl4 but not attenuated by taurine, and classic SASP cytokines (IL-1α/β, IL-6, TNF-α) were not significantly elevated in this model, suggesting IGFBP-1 may represent a distinct, taurine-sensitive senescence-related secretory pathway in the liver.

Taken together, the data propose a taurine–H₂S/IGFBP-1 axis in which taurine reprograms hepatic cysteine metabolism to enhance H₂S production, reducing oxidative stress and senescent cell accumulation, while simultaneously suppressing a pro-senescence hepatokine signal. These complementary mechanisms may explain taurine's broad hepatoprotective and anti-aging effects observed in prior life-span studies.