Molecular signatures of longevity identify compounds that extendmouse lifespan and healthspan
Shindyapina, A. V.; Tyshkovskiy, A.; Bozaykut, P.; Castro, J. P.; Gerashchenko, M. V.; Trapp, A.; Meer, M. V.; Zhang, B.; Poganik, J. R.; Horvath, S.; Miller, R. A.; Gladyshev, V. N.
Show abstract
Longevity interventions in mammals are typically discovered on a case-by-case basis, hindering systematic geroprotector development. We developed a platform for the identification of longevity interventions integrating longevity gene expression biomarkers within and across species, in silico chemical screening, analyses of selected compounds in cell culture, short-term dietary interventions coupled with omics profiling, and ultimately lifespan studies in mice. This approach identified compounds (selumetinib, vorinostat, celastrol, AZD-8055, LY-294002) that extended lifespan and/or healthspan in aged C57BL/6JN male mice, with limited effects in females. In addition, selumetinib and vorinostat increased lifespan when administered to young, genetically heterogeneous UM-HET3 mice. Our biomarker-driven platform accelerates geroprotector discovery, offering a scalable approach to target conserved longevity pathways.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging 95%
- Systems biology and machine learning approaches identify metabolites that influence dietary lifespan and healthspan responses across flies and humans. 95%
- Epigenetic rejuvenation of the hippocampus by environmental enrichment 95%
Similar papers in this journal
- GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging 95%
- Heterochronic parabiosis reprograms the mouse brain transcriptome by shifting aging signatures in multiple cell types 95%
- Ribosomal S6 kinase 1 regulates inflammaging via the senescence secretome 94%
Similar papers in this journal
- Enhancing Mask Activity in Dopaminergic Neurons Extends Lifespan in Flies 95%
- Rapamycin Reverses the Hepatic Response to Diet-Induced Metabolic Stress That Is Amplified by Aging. 95%
- A Trans-Omic Mendelian Randomization Study of Parental Lifespan Uncovers Novel Aging Biology and Drug Candidates for Human Healthspan Extension 95%
Similar papers in this journal
- Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation 96%
- The Neuron-specific IIS/FOXO Transcriptome in Aged Animals Reveals Regulatory Mechanisms of Neuronal and Cognitive Aging 95%
- Overexpression of Ssd1 and calorie restriction extend yeast replicative lifespan by preventing deleterious age-dependent iron uptake 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.