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

Apr 1, 2026EMBO molecular medicine

Tomatidine may improve thinking and reduce aging cells in old mice

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Abstract

Tomatidine, found in tomatoes, is associated with reduced frailty and improved cognitive performance in aged mice.

Tomatidine selectively suppressed the expression of inflammatory factors in senescent human brain cells.
In aged mice, tomatidine reduced markers of cellular aging in liver, skin, and brain tissues.
Functional improvements in motor coordination and cognitive performance were observed in aged mice treated with tomatidine.
Tomatidine decreased neuroinflammation and activation of immune cells in the brain.
The compound improved the integrity of the blood-brain barrier by enhancing tight junction protein expression.

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Cellular senescence drives aging and age-related dysfunction across multiple tissues, including the brain. Through a high-content, senescent cell-based phenotypic screen of a small panel of natural products, we identified tomatidine, an aglycone of tomatine found in tomatoes, as a previously unrecognized senotherapeutic agent. In senescent human brain microvascular endothelial cells and fibroblasts, tomatidine selectively suppressed SASP expression without affecting p16or p21levels consistent with a senomorphic effect. In aged mice, tomatidine reduced frailty and improved motor coordination and cognitive performance. These functional benefits were accompanied by reduced senescence markers (p16, p21, and telomere-associated DNA damage foci) in liver, skin, and hippocampal neurons, along with decreased neuroinflammation and microglial activation. Tomatidine also diminished brain endothelial cell senescence while enhancing tight junction protein expression, suggesting preserved blood-brain barrier integrity. Together, these findings identify tomatidine as a promising senescence-targeting compound with beneficial effects in aged mice and support its further evaluation in mechanistic and translational studies. Ink4a Cip1Ink4a Cip1

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

Abstract

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