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Aerobic Exercise Combined with Multisensory Stimulation Training Improves Cognitive Frailty by Modulating Circulating
Minguang Yang1,2, Yuwei Ye1,2, Liumu Wang3
1National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
International Journal of Molecular Sciences
|May 13, 2026
Summary
Combined training significantly improved cognitive and motor function in aging mice. This intervention boosts the anti-aging protein Klotho, enhancing brain and muscle health for healthier aging.
Area of Science:
- Neuroscience
- Gerontology
- Molecular Biology
Background:
- Cognitive frailty (CF) presents a significant challenge to healthy aging, marked by simultaneous cognitive and motor decline.
- Effective interventions for CF are limited, highlighting the need for novel therapeutic strategies.
- The anti-aging protein Klotho plays a role in brain and muscle health but declines with age.
Purpose of the Study:
- To investigate if combined training (aerobic exercise and multisensory stimulation) can ameliorate age-related cognitive frailty in mice.
- To explore the role of systemic Klotho signaling in mediating the effects of combined training on cognitive and motor function.
- To elucidate the molecular mechanisms underlying the benefits of combined training on hippocampal and skeletal muscle health.
Main Methods:
- A mouse model of age-related cognitive frailty underwent aerobic training, multisensory stimulation, or combined training for 16 months.
- Behavioral, electrophysiological, histological, and molecular assessments were conducted.
- Systemic Klotho expression was inhibited using dual-route shRNA delivery to examine its mechanistic role.
Main Results:
- Combined training significantly improved cognitive and motor performance compared to individual interventions.
- Combined training increased hippocampal dendritic spine density and long-term potentiation, and reduced muscle collagen deposition.
- Upregulation of Klotho, FGF19, and FGFR1 was observed in the hippocampus and muscle, with elevated serum Klotho levels. Klotho knockdown negated these benefits.
Conclusions:
- Combined training effectively alleviates cognitive frailty in aging mice.
- Systemic Klotho is a crucial mediator, linking improved hippocampal synaptic function and skeletal muscle homeostasis.
- This study identifies a promising intervention strategy targeting Klotho signaling for promoting healthy aging.
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