ITP: ITP2020: Interventions Testing Program: Lifespan effects in UM-HET3 mice treated with a-ketoglutarate, canagliflozin, 2,4-dinitrophenol, hydralazine, nebivolol, 16-a-hydroxyestriol, sodium thiosulfate (2024)

Miller RA, Harrison DE, Cortopassi GA, Dehghan I, Fernandez E, Garratt M, Geisler JG, Ginsburg BC, Han ML, Kaczorowski CC, Kumar N, Leiser SF, Lopez-Cruzan M, Milne G, Mitchell JR, Nelson JF, Reifsnyder PC, Salmon AB, Korstanje R, Rosenthal N, Strong R. Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin. Geroscience. 2024 Oct;46(5):4657-4670. doi: 10.1007/s11357-024-01176-2. Epub 2024 May 16.   PubMed 38753230     FullText


         
The Interventions Testing Program (ITP, National Institute on Aging) is a multi-institutional study investigating treatments with the potential to extend lifespan and delay disease and dysfunction in heterogeneous populations of UM-HET3 mice. Such treatments include pharmaceuticals, nutraceuticals, foods, diets, dietary supplements, plant extracts, hormones, peptides, amino acids, chelators, redox agents, and other agents or mixtures of agents. In this study, canagliflozin and 16-a-hydroxyestriol had an effect in males only.

Experimental groups in this study:
• Control     • a-ketoglutarate     • Canagliflozin     • 2,4-dinitrophenol     • Hydralazine     • Nebivolol     • 16-a-hydroxyestriol     • Sodium thiosulfate    

Investigators Richard A Miller       University of Michigan,  Ann Arbor, MI
Randy Strong       University of Texas Health Science Center,  San Antonio, TX
Ron Korstanje       The Jackson Laboratory,  Bar Harbor, ME
David E Harrison       The Jackson Laboratory,  Bar Harbor, ME
Nadia A Rosenthal       The Jackson Laboratory,  Bar Harbor, ME
ContactRichard A Miller     millerr@umich.edu     Lab web site
Affiliated CenterNational Institute on Aging Interventions Testing Program (ITP)
AcknowledgementsFunding provided by NIH AG022303, AG022307, AG022308, AG066346
Project type Phenotype strain survey data set
MPD identifiersITP2020     MPD:1222
Data changelog No updates/corrections.       Initial release date: 03/2025.
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Mice: UM-HET3 population   ♀♂   age various   8 experimental groups

Study results by compound and year

Compound name and (abbreviation) Year
cohort		 Dose in food Age at initiation Compound's
effect on lifespan*		 Other phenotypes
16-a-hydroxyestriol (OH-Est) C2020 5 ppm 12 mo View survival analysis   New
males p = 0.0004
2,4-dinitrophenol (DNP) C2020 3 ppm 6 mo View survival analysis   New
a-Ketoglutarate (AKG) C2020 20,000 ppm 18 mo View survival analysis   New
canagliflozin (Cana) C2020 180 ppm 6 or 16 mo View survival analysis   New
males 6 mo p = 0.0209
males 16 mo p = 0.023
Hydralazine (HYD) C2020 30 ppm 6 or 16 mo View survival analysis   New
Nebivolol (NEBI) C2020 60 ppm 6 mo View survival analysis   New
Sodium thiosulfate (THIO) C2020 10,000 ppm 6 mo View survival analysis   New

* Log-rank test p-value on treated vs. control, shown when p ≤ 0.05 for each sex separately. Statistical definitions