Sestrin1 protects aging livers and aids exercise in mice
In aged mice, lacking Sestrin1 worsened liver cell senescence and fat buildup, and the protein proved indispensable for the liver benefits of exercise.
Journal of Cellular Physiology
In an experiment in C57BL/6J mice across young, middle, and old ages, researchers tracked liver aging alongside mice lacking either the Sestrin1 or Sestrin2 stress-response gene. Natural aging led to progressive declines in both proteins in the liver. Mice lacking Sestrin1 showed significantly worse cell senescence, fat accumulation, oxidative stress, and inflammation than wild-type mice or mice lacking Sestrin2. In cultured mouse liver cells, raising Sestrin1 levels promoted mitochondrial division, reduced the escape of mitochondrial DNA into the cell interior, and suppressed an inflammatory pathway called cGAS-STING. Blocking mitochondrial division stopped these protective actions. Furthermore, exercise training required Sestrin1 to deliver its protective benefits against age-related liver decline in the mice.
Why it matters
Liver function declines with age as cells enter senescence and inflammation rises. Identifying proteins that mediate the protective effects of exercise helps clarify how physical activity preserves organ health during aging.
Caveats
The findings come entirely from mice and cultured mouse liver cells, so whether Sestrin1 plays the same role during human liver aging remains unknown. The precise molecular pathway was tested in cell culture using an inhibitor chemical rather than in living animals.
The paper
Tianjin Medical University
Journal of Cellular Physiology · 1 Oct 2026
