@article{f36672ee6b4a425881095156c811f0c5,
title = "Mitochondrial health is enhanced in rats with higher vs. lower intrinsic exercise capacity and extended lifespan",
abstract = "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.",
author = "Aon, {Miguel A.} and Sonia Cortassa and Magdalena Juhaszova and Gonz{\'a}lez-Reyes, {Jos{\'e} A.} and Miguel Calvo-Rubio and Villalba, {Jos{\'e} M.} and Lachance, {Andrew D.} and Ziman, {Bruce D.} and Mitchell, {Sarah J.} and Murt, {Kelsey N.} and Axsom, {Jessie E.C.} and Irene Alfaras and Britton, {Steven L.} and Koch, {Lauren G.} and {de Cabo}, Rafael and Lakatta, {Edward G.} and Sollott, {Steven J.}",
note = "Funding Information: We are grateful to the following colleagues for their input of information to this work: Dr. Mervyn Maze (University of San Francisco, San Francisco, CA), Dr. John P. Thyfault (University of Kansas Medical Center, Kansas City, Kansas), Dr. Henry J. Thompson (Colorado State University, Fort Collins, CO), and Dr. Colleen M. Novak (Kent State University, Kent, OH). We thank Dr. Michel Bernier for critically reading the manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. The LCR-HCR rat model system is funded by the Office of Research Infrastructure Programs grant P40OD021331 (to L.G.K. and S.L.B.) from the National Institutes of Health. The rat models for low and high exercise capacity are maintained as an international resource with support from the Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH. Contact L.G.K., Lauren.Koch2@UToledo.edu, or S.L.B., brittons@umich.edu, for information on the rat models. Funding Information: The metabolomics data of the present work is available at the NIH Common Fund{\textquoteright}s National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench (https://www.metabolomicsworkbench.org) where it has been assigned Project ID (PR001027). The data can be accessed directly via Project DOI: (10.21228/M8Z41B). This work is supported by NIH grant U2C-DK119886. Further information and requests for resources and reagents should be directed to and will be fulfilled by Steven J. Sollott (sollotts@grc.nia.nih.gov) and Miguel A. Aon (miguel. aon@nih.gov). Publisher Copyright: {\textcopyright} 2021, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",
year = "2021",
month = dec,
doi = "10.1038/s41514-020-00054-3",
language = "English (US)",
volume = "7",
journal = "npj Aging and Mechanisms of Disease",
issn = "2056-3973",
publisher = "Nature Publishing Group",
number = "1",
}