Research Paper Volume 10, Issue 1 pp 34—55
Muscle function decline and mitochondria changes in middle age precede sarcopenia in mice
- 1 Center for Exercise, Metabolism and Cancer, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile
- 2 Department of Cellular and Molecular Biology, School of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
- 3 Center for Genomics and Bioinformatics, Universidad Mayor de Chile, Santiago, Chile
- 4 Physiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile
- 5 Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
Received: July 28, 2017 Accepted: December 30, 2017 Published: January 4, 2018
https://doi.org/10.18632/aging.101358How to Cite
Abstract
Sarcopenia is the degenerative loss of muscle mass and strength with aging. Although a role of mitochondrial metabolism in muscle function and in the development of many diseases has been described, the role of mitochondrial topology and dynamics in the process of muscle aging is not fully understood. This work shows a time line of changes in both mitochondrial distribution and skeletal muscle function during mice lifespan. We isolated muscle fibers from flexor digitorum brevis of mice of different ages. A fusion-like phenotype of mitochondria, together with a change in orientation perpendicular to the fiber axis was evident in the Adult group compared to Juvenile and Older groups. Moreover, an increase in the contact area between sarcoplasmic reticulum and mitochondria was evident in the same group. Together with the morphological changes, mitochondrial Ca2+ resting levels were reduced at age 10-14 months and significantly increased in the Older group. This was consistent with a reduced number of mitochondria-to-jSR pairs in the Older group compared to the Juvenile. Our results support the idea of several age-dependent changes in mitochondria that are accentuated in midlife prior to a complete sarcopenic phenotype.
Abbreviations
SSM: Subsarcolemmal mitochondria; IMF: Intermiofibrillar mitochondria; FDB: Flexor digitalis Brevis; SR: sarcoplasmic reticulum; Mfn1/2: Mitofusin 1 and 2; Opa-1: Optic atrophy type 1 Protein; Drp-1: Dynamin related protein 1; Fis-1: Fission protein 1; COX IV: Cytochrome c Oxidase Subunit IV; RyR1: Ryanodine Receptor; DHPR: Dyhidropyridine Receptor; MCU: Mitochondrial calcium Uniporter.