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This study investigates the long-term effects and cellular mechanisms of resveratrol, fisetin, and senolytics on human healthspan and lifespan using animal model studies.The experimental cohort comprised male C57BL/6 mice randomly assigned to treatment groups: resveratrol, fisetin, senolytics, or control.Lifespan was evaluated using Kaplan-Meier survival analysis, revealing significant extensions in mice treated with resveratrol (p < 0.05) and fisetin (p < 0.05) compared to controls, suggesting their potential to enhance longevity.Furthermore, resveratrol and fisetin treatment demonstrated improvements in healthspan indicators, including physical activity levels, cognitive function, metabolic parameters, and age-related pathologies.Resveratrol-treated mice exhibited increased physical activity levels compared to controls, while fisetin-treated mice showed enhanced cognitive function in spatial memory tasks.Additionally, both resveratrol and fisetin treatment led to improvements in metabolic parameters, such as glucose tolerance and insulin sensitivity, and reductions in age-related pathologies, including inflammation and oxidative damage.Mechanistic analyses revealed distinct cellular pathways underlying the effects of resveratrol, fisetin, and senolytics.Resveratrol activated sirtuins and AMPK signaling pathways, while fisetin exhibited antioxidant, anti-inflammatory, and neuroprotective properties.Senolytics treatment showed trends in reducing senescent cell burden and attenuating age-related decline in tissue function.Despite promising findings, limitations include the use of animal models, which may not fully replicate human aging, and the need for further validation in human populations.Additionally, the specific dosages and treatment regimens used may not directly translate to human applications.Resveratrol, fisetin, and senolytics show promise as interventions for promoting healthy aging and extending lifespan.Further research, including clinical trials in human populations, mechanistic studies, and exploration of combination therapies, is warranted to validate these findings and translate them into clinical practice.Collaborative efforts are crucial to harness the potential of these compounds and improve health outcomes in aging populations.
Ansari et al. (Sat,) studied this question.