Tomatidine is a senotherapeutic compound that improves cognitive function and reduces cellular senescence in aged mice

Here, we identify tomatidine, an aglycone of tomatine naturally found in tomatoes, as a senotherapeutic agent. In vitro, tomatidine selectively suppressed SASP expression without affecting p16Ink4a or p21Cip1 levels in senescent human brain microvascular endothelial cells.

In aged mice, dietary tomatidine reduced frailty and improved motor coordination and cognitive performance. These functional benefits were accompanied by a reduction in senescence markers (e.g., p16, p21, and telomere-associated DNA damage foci) in liver, skin, and hippocampal neurons, as well as decreased neuroinflammation and microglial activation. Tomatidine also reduced senescence in brain endothelial cells and increased the expression of tight junction–associated proteins.