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) in...

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Autores principales:	Miguel A. Aon, Sonia Cortassa, Magdalena Juhaszova, José A. González-Reyes, Miguel Calvo-Rubio, José M. Villalba, Andrew D. Lachance, Bruce D. Ziman, Sarah J. Mitchell, Kelsey N. Murt, Jessie E. C. Axsom, Irene Alfaras, Steven L. Britton, Lauren G. Koch, Rafael de Cabo, Edward G. Lakatta, Steven J. Sollott
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/14634003ef5e447c891b439fccd94408
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spelling	oai:doaj.org-article:14634003ef5e447c891b439fccd944082021-12-02T13:49:53ZMitochondrial health is enhanced in rats with higher vs. lower intrinsic exercise capacity and extended lifespan10.1038/s41514-020-00054-32056-3973https://doaj.org/article/14634003ef5e447c891b439fccd944082021-01-01T00:00:00Zhttps://doi.org/10.1038/s41514-020-00054-3https://doaj.org/toc/2056-3973Abstract 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.Miguel A. AonSonia CortassaMagdalena JuhaszovaJosé A. González-ReyesMiguel Calvo-RubioJosé M. VillalbaAndrew D. LachanceBruce D. ZimanSarah J. MitchellKelsey N. MurtJessie E. C. AxsomIrene AlfarasSteven L. BrittonLauren G. KochRafael de CaboEdward G. LakattaSteven J. SollottNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Miguel A. Aon Sonia Cortassa Magdalena Juhaszova José A. González-Reyes Miguel Calvo-Rubio José M. Villalba Andrew D. Lachance Bruce D. Ziman Sarah J. Mitchell Kelsey N. Murt Jessie E. C. Axsom Irene Alfaras Steven L. Britton Lauren G. Koch Rafael de Cabo Edward G. Lakatta Steven J. Sollott Mitochondrial health is enhanced in rats with higher vs. lower intrinsic exercise capacity and extended lifespan
description	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.
format	article
author	Miguel A. Aon Sonia Cortassa Magdalena Juhaszova José A. González-Reyes Miguel Calvo-Rubio José M. Villalba Andrew D. Lachance Bruce D. Ziman Sarah J. Mitchell Kelsey N. Murt Jessie E. C. Axsom Irene Alfaras Steven L. Britton Lauren G. Koch Rafael de Cabo Edward G. Lakatta Steven J. Sollott
author_facet	Miguel A. Aon Sonia Cortassa Magdalena Juhaszova José A. González-Reyes Miguel Calvo-Rubio José M. Villalba Andrew D. Lachance Bruce D. Ziman Sarah J. Mitchell Kelsey N. Murt Jessie E. C. Axsom Irene Alfaras Steven L. Britton Lauren G. Koch Rafael de Cabo Edward G. Lakatta Steven J. Sollott
author_sort	Miguel A. Aon
title	Mitochondrial health is enhanced in rats with higher vs. lower intrinsic exercise capacity and extended lifespan
title_short	Mitochondrial health is enhanced in rats with higher vs. lower intrinsic exercise capacity and extended lifespan
title_full	Mitochondrial health is enhanced in rats with higher vs. lower intrinsic exercise capacity and extended lifespan
title_fullStr	Mitochondrial health is enhanced in rats with higher vs. lower intrinsic exercise capacity and extended lifespan
title_full_unstemmed	Mitochondrial health is enhanced in rats with higher vs. lower intrinsic exercise capacity and extended lifespan
title_sort	mitochondrial health is enhanced in rats with higher vs. lower intrinsic exercise capacity and extended lifespan
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/14634003ef5e447c891b439fccd94408
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Mitochondrial health is enhanced in rats with higher vs. lower intrinsic exercise capacity and extended lifespan

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