Mild Muscle Mitochondrial Fusion Distress Extends Drosophila Lifespan through an Early and Systemic Metabolome Reorganization.

Data de publicació: 09/11/2021 Data Ahead of Print: 09/11/2021

Autors de IIS La Fe

Marta Isabel Roca Marugán

Autor
Agustín Lahoz Rodríguez

Autor

Autors aliens a IIS La Fe

Tapia A
Palomino-Schätzlein M
Pineda-Lucena A
López Del Amo V
Galindo MI

Grups d'Investigació

Unidad de Biomarcadores y Medicina de Precisión (UBYMP)

Leader

Agustín Lahoz Rodríguez

Abstract

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 Drosophila genes Marf and Opa1, two genes that encode for proteins promoting mitochondrial fusion, orthologues of human MFN2 and OPA1. Silencing of Marf and Opa1 in muscle increases lifespan, improves locomotor capacities in the long term, and maintains muscular integrity. A metabolomic analysis revealed that muscle down-regulation of Marf and Opa1 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 Drosophila 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.

Dades de la publicació

ISSN/ISSNe:: 1661-6596, 1661-6596
Tipus:: Article
Pàgines:: -
DOI:: 10.3390/ijms222212133
PubMed:: 34830014
Factor d'Impacte:: 1,176 SCImago ℠
Quartil:: Q1 SCImago ℠

Documents

No hi ha documents

Mètriques

Filiacions

Tapia A:: Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain
Palomino-Schätzlein M:: Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain
Roca M:: Analytical Unit, Medical Research Institute-Hospital La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
Lahoz A:: Analytical Unit, Medical Research Institute-Hospital La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain

Biomarkers and Precision Medicine Unit, Medical Research Institute-Hospital La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain
Pineda-Lucena A:: Molecular Therapeutics Program, Centro de Investigación Médica Aplicada, Universidad de Navarra, 31008 Pamplona Spain
López Del Amo V:: Section of Cell and Developmental Biology, University of California, San Diego, CA 92093, USA
Galindo MI:: Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain

Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, 46022 Valencia, Spain

UPV-CIPF Joint Unit Disease Mechanisms and Nanomedicine, 46012 Valencia, Spain