Ketogenic diet induces oxidative stress and cellular senescence in male, but not female, mice

Multiple factors involved in ketogenic diet (KD) role in health improvement but the role of sex in KD is not well understood.

The researchers demonstrate that a ketogenic diet induces p53, p21, oxidative stress and cellular senescence in an estrogen-dependent manner, with effects seen in male, but not female, mice.

They also observe KD given to male but not female mice increased markers of oxidative stress and acetylation of mitochondrial proteins, including manganese superoxide dismutase (MnSOD) and reversed by estrogen and antioxidant treatment to male mice.

A similar response was observed with a high-fat diet, suggesting that elevated fatty acid oxidation may contribute to senescence under specific metabolic conditions.

https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00797-1

https://sciencemission.com/Divergent-sex-specific-effects-on-a-ketogenic-diet