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The aging mitochondria, dynamic and protective adaptations of exercise

English title The aging mitochondria, dynamic and protective adaptations of exercise
Applicant Amati Francesca
Number 170062
Funding scheme Project funding (Div. I-III)
Research institution Institute of Sport Science and DSB Université de Lausanne Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Endocrinology
Start/End 01.12.2016 - 29.02.2020
Approved amount 372'000.00
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All Disciplines (3)

Discipline
Endocrinology
Physiology : other topics
Molecular Biology

Keywords (5)

Aging; Mitochondria; Exercise ; Physical activity; Sarcopenia

Lay Summary (French)

Lead
En vieillissant, nous perdons du muscle, devenons plus frêles et ceci peut limiter notre indépendance ainsi que notre qualité de vie. Parmi les acteurs impliqués dans la perte musculaire, se trouvent des petites structures à l’intérieur des cellules, appelées mitochondries, responsables de produire l’énergie nécessaire au fonctionnement des cellules.
Lay summary

Objectifs du travail de recherche

Les mitochondries sont très dynamiques, elles peuvent fusionner, se séparer ou être détruites, en fonction de facteurs environnementaux ou de facteurs génétiques. Ce projet vise à comprendre les mécanismes sous jacents dans les mitochondries qui expliquent les problèmes musculaires liés au vieillissement.  Les chercheurs étudient notamment la pratique d'exercice physique est étudiée car elle permet de prévenir les maladies métaboliques liées au vieillissement qui pourraient être, en partie, expliquées par des dysfonctionnement des mitochondries dans le muscle des séniors.

 

Contexte scientifique du projet de recherche

Ce projet s'inscrit à cheval entre la recherche clinique et la recherche fondamentale. L'équipe de recherche est formée de cliniciens et de biologistes, faisant le pont entre la physiologie du corps et les aspects moléculaires des cellules, pour comprendre les maladies métaboliques liées au vieillissement. 

Direct link to Lay Summary Last update: 28.11.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Spastin mutations impair coordination between lipid droplet dispersion and reticulum
Arribat Yoan, Grepper Dogan, Lagarrigue Sylviane, Qi Timothy, Cohen Sarah, Amati Francesca (2020), Spastin mutations impair coordination between lipid droplet dispersion and reticulum, in PLOS Genetics, 16(4), e1008665-e1008665.
Renal tubular arginase‐2 participates in the formation of the corticomedullary urea gradient and attenuates kidney damage in ischemia‐reperfusion injury in mice
Ansermet Camille, Centeno Gabriel, Lagarrigue Sylviane, Nikolaeva Svetlana, Yoshihara Hikari A., Pradervand Sylvain, Barras Jean‐Luc, Dattner Nicolas, Rotman Samuel, Amati Francesca, Firsov Dmitri (2020), Renal tubular arginase‐2 participates in the formation of the corticomedullary urea gradient and attenuates kidney damage in ischemia‐reperfusion injury in mice, in Acta Physiologica.
Mitochondria in Embryogenesis: An Organellogenesis Perspective
Arribat Yoan, Grepper Dogan, Lagarrigue Sylviane, Richard Joy, Gachet Mélanie, Gut Philipp, Amati Francesca (2019), Mitochondria in Embryogenesis: An Organellogenesis Perspective, in Frontiers in Cell and Developmental Biology, 7, 282.
Tanycytes Regulate Lipid Homeostasis by Sensing Free Fatty Acids and Signaling to Key Hypothalamic Neuronal Populations via FGF21 Secretion
Geller Sarah, Arribat Yoan, Netzahualcoyotzi Citlalli, Lagarrigue Sylviane, Carneiro Lionel, Zhang Lianjun, Amati Francesca, Lopez-Mejia Isabel C., Pellerin Luc (2019), Tanycytes Regulate Lipid Homeostasis by Sensing Free Fatty Acids and Signaling to Key Hypothalamic Neuronal Populations via FGF21 Secretion, in Cell Metabolism, 30(4), 833-844.e7.
Exercise Testing in Individuals With Diabetes, Practical Considerations for Exercise Physiologists
Kosinski Christophe, Besson Cyril, Amati Francesca (2019), Exercise Testing in Individuals With Diabetes, Practical Considerations for Exercise Physiologists, in Frontiers in Physiology, 10, 1257.
Reassessing the Role of Diacylglycerols in Insulin Resistance
Jayasinghe Sisitha U., Tankeu Aurel T., Amati Francesca (2019), Reassessing the Role of Diacylglycerols in Insulin Resistance, in Trends in Endocrinology & Metabolism, 30(9), 618-635.
Molecular codes and in vitro generation of hypocretin and melanin concentrating hormone neurons
Seifinejad Ali, Li Sha, Mikhail Cyril, Vassalli Anne, Pradervand Sylvain, Arribat Yoan, Pezeshgi Modarres Hassan, Allen Bridget, John Rosalind M., Amati Francesca, Tafti Mehdi (2019), Molecular codes and in vitro generation of hypocretin and melanin concentrating hormone neurons, in Proceedings of the National Academy of Sciences, 116(34), 17061-17070.
Hybrid fiber alterations in exercising seniors suggest contribution to fast‐to‐slow muscle fiber shift
Moreillon Maxime, Conde Alonso Sonia, Broskey Nicholas T., Greggio Chiara, Besson Cyril, Rousson Valentin, Amati Francesca (2019), Hybrid fiber alterations in exercising seniors suggest contribution to fast‐to‐slow muscle fiber shift, in Journal of Cachexia, Sarcopenia and Muscle, 10(3), 687-695.
Thigh and abdominal adipose tissue depot associations with testosterone levels in postmenopausal females
Ofori Emmanuel K., Conde Alonso Sonia, Correas-Gomez Lorena, Carnero Elvis A., Zwygart Karin, Hugues Henry, Bardy Daniel, Hans Didier, Dwyer Andrew A., Amati Francesca (2019), Thigh and abdominal adipose tissue depot associations with testosterone levels in postmenopausal females, in Clinical Endocrinology, 90(3), 433-439.
Distinct patterns of skeletal muscle mitochondria fusion, fission and mitophagy upon duration of exercise training
Arribat Yoan, Broskey Nicholas T., Greggio Chiara, Boutant Marie, Conde Alonso Sonia, Kulkarni Sameer S., Lagarrigue Sylviane, Carnero Elvis A., Besson Cyril, Cantó Carles, Amati Francesca (2019), Distinct patterns of skeletal muscle mitochondria fusion, fission and mitophagy upon duration of exercise training, in Acta Physiologica, 225(2), e13179-e13179.
Mitochondrial respiratory states and rates - Preprint arch
(2019), Mitochondrial respiratory states and rates - Preprint arch, MitoFit Preprint Arch, Austria.
Enhanced Respiratory Chain Supercomplex Formation in Response to Exercise in Human Skeletal Muscle
Greggio Chiara, Jha Pooja, Kulkarni Sameer S., Lagarrigue Sylviane, Broskey Nicholas T., Boutant Marie, Wang Xu, Conde Alonso Sonia, Ofori Emmanuel, Auwerx Johan, Cantó Carles, Amati Francesca (2017), Enhanced Respiratory Chain Supercomplex Formation in Response to Exercise in Human Skeletal Muscle, in Cell Metabolism, 25(2), 301-311.

Collaboration

Group / person Country
Types of collaboration
Orian S. Shirihai and Marc Liesa, Department of Molecular and Medical Pharmacology, UCLA United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Dmitri Firsov, Department of Pharmacology and Toxicology, UNIL Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Alexandre Reymond, Center for Integrative Genomics, UNIL Switzerland (Europe)
- Research Infrastructure
Mehdi Tafti, Department of Physiology, UNIL Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Christian Widmann, Department of Physiology, UNIL Switzerland (Europe)
- Research Infrastructure
Luc Pellerin, Department of Physiology, UNIL Switzerland (Europe)
- Publication
- Research Infrastructure
Carles Cantó, Nestlé Research, Nestlé Institute of Health Sciences Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Marie-Catherine Vozenin, Radiation therapy, CHUV Switzerland (Europe)
- Research Infrastructure
Philipp Gut, Nestlé Research, Nestlé Institute of Health Sciences Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Nadia Mercader, Institute of Anatomy, UNIBE Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
FASEB Science Research Conference Talk given at a conference The Mitochondrial Biogenesis and Dynamics in Health and Disease 19.05.2019 Palm Springs, CA, United States of America Amati Francesca;
SwissZebra annual meeting Talk given at a conference Time-course effect of exercise on zebrafish muscle (Oral presentation, Nicola Regazzi) 05.04.2019 Leukerbad, Switzerland Lagarrigue Sylviane; Amati Francesca;
SwissZebra annual meeting Talk given at a conference Mitochondria in embryogenesis: an organellogenesis perspective (Oral presentation, Dogan Grepper) 05.04.2019 Leukerbad, Switzerland Amati Francesca; Lagarrigue Sylviane;
Keystone symposium Talk given at a conference Mitochondria and substrate switches, novel mechanistic insights 13.01.2019 Keystone, CO, United States of America Amati Francesca;
Swiss Sport medicine conference Poster Fast to Slow Muscle Fiber Shift and Parallel Hybrid Fiber Alterations in Exercising Seniors (Maxime Moreillon) 15.11.2018 Bern, Switzerland Amati Francesca;
12th Swiss Meeting on muscle research Talk given at a conference Evidence of a novel mitophagic pathway in human skeletal muscle 04.11.2018 Magglingen, Switzerland Amati Francesca;
EMBO workshop Poster Perilipins: at the crossroad of organelle communication (Yoan Arribat) 21.09.2018 Arosa, Switzerland Lagarrigue Sylviane; Amati Francesca;
Europhysiology congress Talk given at a conference Effects of exercise on mitochondria respiratory supercomplex assemblies 14.09.2018 London, Great Britain and Northern Ireland Amati Francesca;
Annual meeting of the American College of Sports Medicine Poster Muscle Fiber Type Adaptations To Exercise Differ In Obese And Non-obese Volunteers (Maxime Moreillon) 29.05.2018 Mineapolis, MN, United States of America Amati Francesca;
SwissZebra annual meeting Talk given at a conference Origin and organisation of mitochondria in embryogenesis (Oral presentation, Yoan Arribat) 18.05.2018 Lausanne, Switzerland Lagarrigue Sylviane; Amati Francesca;
British physiological society Symposium: Mitochondria form and function Talk given at a conference Exercise and skeletal muscle mitochondria 15.09.2017 London, Great Britain and Northern Ireland Amati Francesca;
EASD/ADA symposium, European Association for the Study of Diabetes scientific meeting Talk given at a conference Structural changes of mitochondria in response to aerobic exercise training 13.09.2017 Lisbon, Portugal Amati Francesca;
Cell Symposia on Exercise Metabolism Talk given at a conference Mitophagy, fusion and fission response patterns to chronic exercise in human skeletal muscle 21.05.2017 Gothenburgh, Sweden Amati Francesca;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Téléthon Performances, exhibitions (e.g. for education institutions) 09.12.2018 Lausanne, Switzerland Lagarrigue Sylviane;


Communication with the public

Communication Title Media Place Year
Media relations: radio, television RSI, Falò, Invecchiare in forma, è possibile? RSI Italian-speaking Switzerland 2018
Media relations: radio, television RTS, 36.9°, L’Amérique à vélo : l’incroyable défi d’une ex-sédentaire. RTS Western Switzerland 2018
Media relations: radio, television RTS, 36.9°, Vieillir Musclé. RTS Western Switzerland 2018
Media relations: radio, television RTS la 1ère, CQFD, Les frileux en vedette RTS la 1ère Western Switzerland 2017
Media relations: print media, online media Active Voice: Muscle gets better with age - enhanced oxidative capacity in lifelong endurance athle Sport Medicine Bulletin “Active Voice” International 2016
Media relations: radio, television 19h30, Le sport a des effets bénéfiques pour les seniors TSR Western Switzerland 2016
Media relations: radio, television RTS la 1ère, CQFD, Il n’y a pas d’âge pour les bienfaits du sport RTS la 1ère Western Switzerland 2016

Associated projects

Number Title Start Funding scheme
149779 Multi-nuclear magnetic resonance spectroscopy (MRS) and imaging (MRI) on a clinical whole-body MR-system: Lipid organelles and mitochondria 01.12.2013 Project funding (Div. I-III)
175984 Metabolic Fingerprints from Magnetic Resonance: Levels, Maps, and Microstructure 01.12.2017 Project funding (Div. I-III)
188789 Molecular mechanisms of mitochondrial adaptation in muscle metabolism: from human to fish 01.03.2020 Project funding (Div. I-III)
149398 Insulin resistance of aging, ectopic lipid depositions and oxidative capacity: effects of exercise and obesity 01.10.2013 Ambizione

Abstract

Aging is associated with alterations in skeletal muscle metabolism that are thought to play a role in age-related metabolic diseases. Mitochondrial dysfunction is proposed to play a central role in this age-related physiological decline. Mitochondria are cellular organelles that produce most of the chemical energy for cellular sustainment. In muscle, mitochondria are critically needed to generate energy for contraction and thus movement and locomotion. Mitochondria are highly adaptable; they respond to environmental challenges by increasing or decreasing in numbers as well as in their content, and/or becoming more or less efficient. Mitochondrial dynamic processes include the possibility to be newly generated, fused, divided (called fission) or to be discarded by mitochondria targeted autophagy (called mitophagy). The physiological and molecular mechanisms regulating this equilibrium and the adaption of this process during aging remain unknown. Although lifestyle patterns are thought to influence gene-expression signatures in mitochondrial adaptations, findings from human interventional studies conducted in this field are limited. In addition to the dynamic changes described above, the structural/functional organization of the electron transport chain plastically changes from freely moving to super-assembled structures, called supercomplexes. Very little is known on the impact of aging and exercise on these functional adaptations. We propose to investigate mitochondria functional adaptations through aging and exercise.To respond to these aims, we will use skeletal muscle and cultured myocytes from younger and older volunteers that will be thoroughly phenotyped in terms of body composition, non-invasive oxidative phosphorylation, oxygenation capacities and insulin sensitivity, both before and after an exercise intervention. Due to the mechanistic limitations of the human model, we will supplement the clinical part with the use of skeletal muscle from zebrafish. Focusing on aging muscle is crucial. Indeed, aging is not only a critical medical challenge, but aging muscle is often cornerstone in healthy aging. Sarcopenia consequences, such as frailty and mobility impairment, are implicated in falls, loss of independence and cost of care. In addition to preventive and therapeutic benefits, physical activity and exercise interventions have been proven to be cost-effective. These insights into mitochondrial biology will not only advance our knowledge of biological mechanisms underlying human longevity, but also provide insights into extending healthy life span.
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