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Orienteering as a Tool for Cognitive Research: An Implementation Guide

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Aerobic Exercise Combined with Multisensory Stimulation Training Improves Cognitive Frailty by Modulating Circulating

Minguang Yang^1,2, Yuwei Ye^1,2, 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

This summary is machine-generated.

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.

Keywords:

FGFR1 Klotho cognitive frailty hippocampus skeletal muscle

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Published on: October 6, 2016

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.