The African killifish: A short‐lived vertebrate model to study the biology of sarcopenia and longevity

Author:

Ruparelia Avnika A.123ORCID,Salavaty Adrian14,Barlow Christopher K.56,Lu Yansong1,Sonntag Carmen1,Hersey Lucy1,Eramo Matthew J.7,Krug Johannes8,Reuter Hanna8,Schittenhelm Ralf B.56,Ramialison Mirana14,Cox Andrew910,Ryan Michael T.7,Creek Darren J.611,Englert Christoph812ORCID,Currie Peter D.113ORCID

Affiliation:

1. Australian Regenerative Medicine Institute, Monash University Clayton Australia

2. Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine Dentistry and Health Sciences University of Melbourne Melbourne Australia

3. Centre for Muscle Research, Department of Anatomy and Physiology University of Melbourne Melbourne Australia

4. Systems Biology Institute Australia, Monash University Clayton Australia

5. Department of Biochemistry and Molecular Biology Monash University Clayton Australia

6. Monash Proteomics and Metabolomics Facility Monash Biomedicine Discovery Institute, Monash University Clayton Australia

7. Department of Biochemistry and Molecular Biology Monash Biomedicine Discovery Institute, Monash University Clayton Australia

8. Leibniz Institute on Aging—Fritz Lipmann Institute (FLI) Jena Germany

9. Peter MacCallum Cancer Centre Melbourne Australia

10. Department of Biochemistry and Pharmacology The University of Melbourne Melbourne Australia

11. Drug Delivery, Disposition and Dynamics Monash Institute of Pharmaceutical Sciences, Monash University Parkville Australia

12. Institute of Biochemistry and Biophysics, Friedrich‐Schiller‐University Jena Jena Germany

13. EMBL Australia, Victorian Node Monash University Clayton Australia

Abstract

AbstractSarcopenia, the age‐related decline in muscle function, places a considerable burden on health‐care systems. While the stereotypic hallmarks of sarcopenia are well characterized, their contribution to muscle wasting remains elusive, which is partly due to the limited availability of animal models. Here, we have performed cellular and molecular characterization of skeletal muscle from the African killifish—an extremely short‐lived vertebrate—revealing that while many characteristics deteriorate with increasing age, supporting the use of killifish as a model for sarcopenia research, some features surprisingly reverse to an “early‐life” state in the extremely old stages. This suggests that in extremely old animals, there may be mechanisms that prevent further deterioration of skeletal muscle, contributing to an extension of life span. In line with this, we report a reduction in mortality rates in extremely old killifish. To identify mechanisms for this phenomenon, we used a systems metabolomics approach, which revealed that during aging there is a striking depletion of triglycerides, mimicking a state of calorie restriction. This results in the activation of mitohormesis, increasing Sirt1 levels, which improves lipid metabolism and maintains nutrient homeostasis in extremely old animals. Pharmacological induction of Sirt1 in aged animals was sufficient to induce a late life‐like metabolic profile, supporting its role in life span extension in vertebrate populations that are naturally long‐lived. Collectively, our results demonstrate that killifish are not only a novel model to study the biological processes that govern sarcopenia, but they also provide a unique vertebrate system to dissect the regulation of longevity.

Funder

National Health and Medical Research Council

Publisher

Wiley

Subject

Cell Biology,Aging

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