期刊
NPJ AGING AND MECHANISMS OF DISEASE
卷 7, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41514-020-00054-3
关键词
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资金
- Intramural Research Program of the National Institutes of Health, National Institute on Aging
- Office of Research Infrastructure Programs from the National Institutes of Health [P40OD021331]
- Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH
The study revealed that the intrinsic exercise capacity of rats is associated with improved mitochondrial health in cardiomyocytes, leading to extended longevity. These findings may serve as predictors of health and survival outcomes in other populations.
The intrinsic aerobic capacity of an organism is thought to play a role in aging and longevity. Maximal respiratory rate capacity, a metabolic performance measure, is one of the best predictors of cardiovascular- and all-cause mortality. Rats selectively bred for high-(HCR) vs. low-(LCR) intrinsic running-endurance capacity have up to 31% longer lifespan. We found that positive changes in indices of mitochondrial health in cardiomyocytes (respiratory reserve, maximal respiratory capacity, resistance to mitochondrial permeability transition, autophagy/mitophagy, and higher lipids-over-glucose utilization) are uniformly associated with the extended longevity in HCR vs. LCR female rats. Cross-sectional heart metabolomics revealed pathways from lipid metabolism in the heart, which were significantly enriched by a select group of strain-dependent metabolites, consistent with enhanced lipids utilization by HCR cardiomyocytes. Heart-liver-serum metabolomics further revealed shunting of lipidic substrates between the liver and heart via serum during aging. Thus, mitochondrial health in cardiomyocytes is associated with extended longevity in rats with higher intrinsic exercise capacity and, probably, these findings can be translated to other populations as predictors of outcomes of health and survival.
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