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The Combination of Two Small Molecules Improves Neurological Parameters and Extends the Lifespan of C3H Strain Female Mice
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The Combination of Two Small Molecules Improves Neurological Parameters and Extends the Lifespan of C3H Strain Female Mice
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Journal Article
The Combination of Two Small Molecules Improves Neurological Parameters and Extends the Lifespan of C3H Strain Female Mice
2025
Overview
Objectives Targeting partial cellular reprogramming pathways through specific small molecule combinations holds promise for lifespan extension in model organisms. Chemical cocktails like RepSox and tranylcypromine (TCP) may induce beneficial age‐related changes without the risks of full reprogramming. This study investigated the effects of RepSox and TCP on neurological markers, physical activity, skeletal health, and survival in aging C3H female mice. Methods Female C3H mice were divided into two age groups: “old” (16–20 months) and “senior” (10–13 months). They received intraperitoneal injections of RepSox (5 mg/kg) and TCP (3 mg/kg) or DMSO (control) every 72 h for 30 days. Physiological state, neurological scores, open field test performance, skeletal deformation, and survival were assessed. Histological analyses of organs (brain, liver, heart, kidneys, lungs, muscles) were performed post‐treatment. Statistical analyses included Mann‐Whitney tests, mixed‐effects linear regression, Kaplan‐Meier survival analysis, and the Gao‐Allison test. Findings In the “old” group, treated mice showed enhanced neurological status, fur and skeletal health, and increased cortical angiogenesis, though with some adverse histological changes in the liver and brain. In the “senior” group, treated mice displayed a plateau in mortality after month seven, while deaths continued in controls. Although overall survival was not significantly different, maximum lifespan significantly increased in treated mice (p = 0.039, Gao‐Allison test). Histological findings revealed localized adaptive changes rather than major toxic effects. These results suggest that the combination of RepSox and TCP exerts protective effects on aging phenotypes and may potentially slow systemic aging processes in C3H mice. The small molecules RepSox and TCP were investigated for their geroprotective effects in aging C3H mice through intraperitoneal administration. Treatment resulted in improved neurological markers and physical parameters in older mice (16‐20 months), while younger treated mice (10‐13 months) showed increased maximum lifespan compared to controls. These findings suggest that targeting partial cellular reprogramming pathways with specific small molecule combinations may offer therapeutic potential for age‐related decline.
