Hepatic stellate cells (the primary drivers of liver fibrosis) accumulate senescent phenotypes in NASH and NAFLD. Paradoxically, stellate cell senescence can be both fibrosis-limiting (activated stellate cells senesce and stop making collagen) and disease-promoting (their SASP activates neighboring cells and promotes inflammation). Selective clearance of the SASP-producing fraction offers therapeutic potential.

Can senolytics reverse liver fibrosis?

Animal model data shows reduction in established fibrosis with senolytic treatment. Human evidence is limited. Fibrosis reversal requires prolonged treatment and may be more achievable in early (F1–F2) than advanced (F3–F4) fibrosis.