Mild Muscle Mitochondrial Fusion Distress Extends <i>Drosophila</i> Lifespan through an Early and Systemic Metabolome Reorganization

In a global aging population, it is important to understand the factors affecting systemic aging and lifespan. Mitohormesis, an adaptive response caused by different insults affecting the mitochondrial network, triggers a response from the nuclear genome inducing several pathways that promote longev...

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Autores principales:	Andrea Tapia, Martina Palomino-Schätzlein, Marta Roca, Agustín Lahoz, Antonio Pineda-Lucena, Víctor López del Amo, Máximo Ibo Galindo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mitohormesis metabolomics lifespan <i>Drosophila</i> insulin pathway Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/d57201e3bf48444792557d70fa8d30f1
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spelling	oai:doaj.org-article:d57201e3bf48444792557d70fa8d30f12021-11-25T17:53:41ZMild Muscle Mitochondrial Fusion Distress Extends <i>Drosophila</i> Lifespan through an Early and Systemic Metabolome Reorganization10.3390/ijms2222121331422-00671661-6596https://doaj.org/article/d57201e3bf48444792557d70fa8d30f12021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12133https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067In a global aging population, it is important to understand the factors affecting systemic aging and lifespan. Mitohormesis, an adaptive response caused by different insults affecting the mitochondrial network, triggers a response from the nuclear genome inducing several pathways that promote longevity and metabolic health. Understanding the role of mitochondrial function during the aging process could help biomarker identification and the development of novel strategies for healthy aging. Herein, we interfered the muscle expression of the <i>Drosophila</i> genes <i>Marf</i> and <i>Opa1</i>, two genes that encode for proteins promoting mitochondrial fusion, orthologues of human <i>MFN2</i> and <i>OPA1</i>. Silencing of <i>Marf</i> and <i>Opa1</i> in muscle increases lifespan, improves locomotor capacities in the long term, and maintains muscular integrity. A metabolomic analysis revealed that muscle down-regulation of <i>Marf</i> and <i>Opa1</i> promotes a non-autonomous systemic metabolome reorganization, mainly affecting metabolites involved in the energetic homeostasis: carbohydrates, lipids and aminoacids. Interestingly, the differences are consistently more evident in younger flies, implying that there may exist an anticipative adaptation mediating the protective changes at the older age. We demonstrate that mild mitochondrial muscle disturbance plays an important role in <i>Drosophila</i> fitness and reveals metabolic connections between tissues. This study opens new avenues to explore the link of mitochondrial dynamics and inter-organ communication, as well as their relationship with muscle-related pathologies, or in which muscle aging is a risk factor for their appearance. Our results suggest that early intervention in muscle may prevent sarcopenia and promote healthy aging.Andrea TapiaMartina Palomino-SchätzleinMarta RocaAgustín LahozAntonio Pineda-LucenaVíctor López del AmoMáximo Ibo GalindoMDPI AGarticlemitohormesismetabolomicslifespan<i>Drosophila</i>insulin pathwayBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12133, p 12133 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mitohormesis metabolomics lifespan <i>Drosophila</i> insulin pathway Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	mitohormesis metabolomics lifespan <i>Drosophila</i> insulin pathway Biology (General) QH301-705.5 Chemistry QD1-999 Andrea Tapia Martina Palomino-Schätzlein Marta Roca Agustín Lahoz Antonio Pineda-Lucena Víctor López del Amo Máximo Ibo Galindo Mild Muscle Mitochondrial Fusion Distress Extends <i>Drosophila</i> Lifespan through an Early and Systemic Metabolome Reorganization
description	In a global aging population, it is important to understand the factors affecting systemic aging and lifespan. Mitohormesis, an adaptive response caused by different insults affecting the mitochondrial network, triggers a response from the nuclear genome inducing several pathways that promote longevity and metabolic health. Understanding the role of mitochondrial function during the aging process could help biomarker identification and the development of novel strategies for healthy aging. Herein, we interfered the muscle expression of the <i>Drosophila</i> genes <i>Marf</i> and <i>Opa1</i>, two genes that encode for proteins promoting mitochondrial fusion, orthologues of human <i>MFN2</i> and <i>OPA1</i>. Silencing of <i>Marf</i> and <i>Opa1</i> in muscle increases lifespan, improves locomotor capacities in the long term, and maintains muscular integrity. A metabolomic analysis revealed that muscle down-regulation of <i>Marf</i> and <i>Opa1</i> promotes a non-autonomous systemic metabolome reorganization, mainly affecting metabolites involved in the energetic homeostasis: carbohydrates, lipids and aminoacids. Interestingly, the differences are consistently more evident in younger flies, implying that there may exist an anticipative adaptation mediating the protective changes at the older age. We demonstrate that mild mitochondrial muscle disturbance plays an important role in <i>Drosophila</i> fitness and reveals metabolic connections between tissues. This study opens new avenues to explore the link of mitochondrial dynamics and inter-organ communication, as well as their relationship with muscle-related pathologies, or in which muscle aging is a risk factor for their appearance. Our results suggest that early intervention in muscle may prevent sarcopenia and promote healthy aging.
format	article
author	Andrea Tapia Martina Palomino-Schätzlein Marta Roca Agustín Lahoz Antonio Pineda-Lucena Víctor López del Amo Máximo Ibo Galindo
author_facet	Andrea Tapia Martina Palomino-Schätzlein Marta Roca Agustín Lahoz Antonio Pineda-Lucena Víctor López del Amo Máximo Ibo Galindo
author_sort	Andrea Tapia
title	Mild Muscle Mitochondrial Fusion Distress Extends <i>Drosophila</i> Lifespan through an Early and Systemic Metabolome Reorganization
title_short	Mild Muscle Mitochondrial Fusion Distress Extends <i>Drosophila</i> Lifespan through an Early and Systemic Metabolome Reorganization
title_full	Mild Muscle Mitochondrial Fusion Distress Extends <i>Drosophila</i> Lifespan through an Early and Systemic Metabolome Reorganization
title_fullStr	Mild Muscle Mitochondrial Fusion Distress Extends <i>Drosophila</i> Lifespan through an Early and Systemic Metabolome Reorganization
title_full_unstemmed	Mild Muscle Mitochondrial Fusion Distress Extends <i>Drosophila</i> Lifespan through an Early and Systemic Metabolome Reorganization
title_sort	mild muscle mitochondrial fusion distress extends <i>drosophila</i> lifespan through an early and systemic metabolome reorganization
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d57201e3bf48444792557d70fa8d30f1
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Mild Muscle Mitochondrial Fusion Distress Extends <i>Drosophila</i> Lifespan through an Early and Systemic Metabolome Reorganization

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