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Dasatinib plus quercetin attenuates some frailty characteristics in SAMP10 mice
1Advanced Research Center for Geriatric and Gerontology, Akita University, 1-1-1 Hondo, Akita, 010-8543, Japan. hidetaka-ota@med.akita-u.ac.jp.
Abstract:
Senolytics are a class of drugs that selectively remove senescent cells. Dasatinib and quercetin have been discovered, and their combination has shown various anti-ageing effects. The SAMP10 mouse strain is a model of brain ageing. Here, we investigated the effect of combination on frailty characteristics in SAMP10. By comparing SAMP10 with SAMR1 mice as normal ageing controls, we investigated some frailty characteristics. Frailty was assessed at 18-38 weeks of age with a clinical frailty index. Motor and cognitive function of these mice were evaluated using behavioral experiments. SAMP10 mice were divided into vehicle and combination, and these functions and histological changes in the brain hippocampus were investigated. Finally, the in vitro effects of combination on oxidative stress-induced senescent muscle and neuronal cells were investigated. As a result, we found that frailty index was higher in SAMP10 than SAMR1. Motor and cognitive function were worse in SAMP10 than SAMR1. Furthermore, combination therapy improved frailty, motor and cognitive function, and the senescent phenotype of the hippocampus compared with vehicle in SAMP10. In summary, SAMP10 showed more marked frailty characteristics than SAMR1, and dasatinib and quercetin attenuated them in SAMP10. From our results, senolytic therapy might contribute protective effects against frailty.
Insights
Senolytic drugs, dasatinib and quercetin, reduced frailty and improved brain function in aging mice. This senolytic therapy shows promise for combating age-related decline and frailty.
Area of Science:
- Gerontology
- Pharmacology
- Neuroscience
Background:
- Senolytics selectively eliminate senescent cells, offering potential anti-aging benefits.
- The combination of dasatinib and quercetin exhibits various anti-aging effects.
- The SAMP10 mouse strain serves as a model for studying brain aging and associated frailty.
Purpose of the Study:
- To investigate the effects of dasatinib and quercetin combination therapy on frailty characteristics in SAMP10 mice.
- To compare frailty, motor, and cognitive functions between aging SAMP10 mice and normal aging SAMR1 controls.
- To evaluate the impact of senolytic therapy on hippocampal histology and in vitro cellular senescence.
Main Methods:
- Assessment of frailty using a clinical frailty index in SAMP10 and SAMR1 mice (18-38 weeks).
- Evaluation of motor and cognitive functions through behavioral experiments.
- Histological examination of the brain hippocampus and in vitro studies on oxidative stress-induced senescent cells.
Main Results:
- SAMP10 mice exhibited higher frailty index and poorer motor/cognitive function compared to SAMR1 mice.
- Combination therapy significantly improved frailty, motor, and cognitive functions in SAMP10 mice.
- Senolytic treatment attenuated the senescent phenotype in the hippocampus of SAMP10 mice.
Conclusions:
- SAMP10 mice display pronounced frailty characteristics, which are ameliorated by dasatinib and quercetin.
- Senolytic therapy demonstrates protective effects against age-related frailty and cognitive decline.
- This study supports the potential of senolytic interventions in managing aging-related conditions.
