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

ABSTRACT: 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 p16Ink4a or p21Cip1 levels 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 Ink4a, p21 Cip1, and telomere-associated DNA damage foci) in liver, skin, and hippocam

SUBMITTER: Diana Jurk 

PROVIDER: S-SCDT-10_1038-S44321-026-00400-0 | biostudies-other |

REPOSITORIES: biostudies-other