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Basic Science and Pathogenesis.
Riley E Kemna1,2, Amanda Szabo-Reed1, Paul J Kueck1
1University of Kansas Alzheimer's Disease Research Center, Fairway, KS, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
Summary
This study reveals sex-based differences in mitochondrial health and physical fitness among older adults, impacting exercise benefits and Alzheimer
Area of Science:
- Gerontology and Exercise Science
- Cellular Biology and Neuroscience
- Alzheimer's Disease Research
Background:
- Sedentary lifestyles increase Alzheimer's Disease (AD) risk, while exercise offers neuroprotection.
- Female sex is associated with lower physical fitness, potentially influencing AD risk and exercise benefits.
- Understanding cellular mechanisms of fitness in older adults is crucial for AD risk mitigation.
Purpose of the Study:
- To explore cellular mechanisms underlying physical fitness in cognitively healthy older adults.
- To investigate the relationship between exercise, mitochondrial health, and Alzheimer's Disease (AD) risk.
- To examine how sex influences physical fitness, mitochondrial health, and potential exercise benefits.
Main Methods:
- Collected blood samples from 34 cognitively healthy older adults (age 65+) participating in the COMET trial.
- Assessed physical fitness via graded exercise tests and body composition using dual-energy X-ray absorptiometry.
- Isolated lymphocytes, stained them with fluorescent markers, and analyzed mitochondrial health using flow cytometry to derive a mitochondrial health index (MHI).
Main Results:
- Males exhibited higher lean mass, peak oxygen uptake (VO2peak), and a higher mitochondrial health index (MHI) compared to females.
- In males, MHI declined with age; in females, mitochondrial reactive oxygen species (ROS) negatively correlated with lean mass and oxygen uptake efficiency slope (OUES).
- Significant sex-based differences were observed in mitochondrial health and its relationship with physical fitness parameters.
Conclusions:
- Sex-specific differences in mitochondrial health and reactive oxygen species (ROS) influence exercise response.
- These findings suggest that variable responses to exercise training between males and females may contribute to sex differences in Alzheimer's Disease (AD) risk.
- The study highlights the importance of considering sex as a biological variable in exercise interventions for cognitive health.
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