Catalyst Awardee

Project Description

Exercise and Brain Health: Pre-clinical Study of the Energy Transfer Hypothesis of Aging using PET/MRI imaging

Lauren Gerard Koch, PhD | The University of Toledo; Xin Yu, Sc.D. | Case Western Reserve University; Steven L. Britton, Ph.D. |  University of Michigan
Competition Sponsor: US National Academy of Medicine
Awardee Year: 2022

There is a strong link between high aerobic energy capacity and the increase in resilience to developing complex disease with aging, including Alzheimer’s disease and dementia. From this association, we initiated the Energy Transfer Hypothesis of Aging (ETH) that states: Variation in capacity for aerobic energy transfer is the central mechanistic determinant of the divide between aging and longevity. As an unbiased test of the ETH, we performed two large-scale artificial selective breeding experiments in rats for low and high intrinsic (inborn) aerobic treadmill running capacity, and for low and high response to aerobic exercise training. The ETH can be accepted with high confidence given that over 125 published studies performed at ~60 institutions in 11 countries uniformly demonstrate the overall divide for age-related disease risks between low and high exercise capacity rats. We argue that commonly used animal models with induced single gene mutations are too simplistic for understanding features that are driven by multiple gene and environment interactions, such as healthy aging. Rather, our theory-based rat models are thus transformative in the sense of realistically emulating the wide range of exercise capacities as a predictor of the large divide in features underlying healthy aging. Here we will utilize our four exercise rat models to test the medical recommendation of habitual exercise for maintaining brain health. Using PET/MRI imaging, our pre-clinical study will measure for the first time changes in blood flow, metabolism, structural integrity, and waste removal in the brain as a result of habitual exercise across lifetime.


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