MassIVE MSV000086195

Complete Public PXD021652

Skeletal Muscle Proteomics of High Functioning Octogenarians

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Description

Skeletal muscle mass and function decline more precipitously after the age 75 y. To provide insights into biologically relevant mechanisms for preserving muscle mass and physical function in advanced age, a battery of physical function tests, muscle cross-sectional area by MRI and a vastus lateralis muscle biopsy were performed in 15 octogenarian world class track and field masters athletes (MA) and 14 non-athlete age- and sex-matched controls (NA). Muscle samples were analyzed using liquid-chromatography mass spectrometry to generate proteomics data, by histochemistry to identify respiratory compromised muscle fibers, and by quantitative real-time polymerase chain reaction to estimate mtDNA copy number. Physical function and muscle cross-sectional area were higher in MA than NA. Of nearly 6,000 proteins identified and quantified in muscle biopsy specimens, ~800 were differentially represented in MA versus NA. Most of the differentially represented proteins related to mitochondrial structure and function and were overrepresented in muscle of MA versus controls, including TCA cycle, respiratory electron transport capacity (ETC), cristae formation, sirtuins, and 8 mtDNA-encoded proteins. On the contrary, proteins from the spliceosome complex and nuclear pore were downregulated in MA. Consistent with proteomics, MA had fewer respiratory compromised fibers, higher mtDNA copy number, and an increased protein ratio of the cristae-bound ETC subunits relative to the outer mitochondrial membrane protein voltage dependent anion channel. In conclusion, high physical function in advanced age is associated with preservation of mitochondrial health and function, with underrepresentation of proteins that process pre-RNA and determine splicing variants, and underrepresentation of nuclear pore proteins. [doi:10.25345/C5QJ42] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Octogenarians, Master Athlete, Mitochondria, Spliceosome, Skeletal Muscle, Aging, Exercise, Physical Activity, Nuclear pore

Contact

Principal Investigators:
(in alphabetical order) 		Luigi Ferrucci, National Institute on Aging, United States
Russell T. Hepple, Department of Physical Therapy and Department of Physiology & Functional Genomics, University of Florida, United States
Submitting User: Mohien

Publications

Ubaida-Mohien C, Spendiff S, Lyashkov A, Moaddel R, MacMillan NJ, Filion ME, Morais JA, Taivassalo T, Ferrucci L, Hepple RT.
Unbiased proteomics, histochemistry, and mitochondrial DNA copy number reveal better mitochondrial health in muscle of high-functioning octogenarians.
Elife. Epub 2022 Apr 11.

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