Unbiased Proteomics Supports a Key Role for Mitochondria in Skeletal Muscle of Highly Functioning Octogenarians
Bibliographic record
Abstract
Introduction Skeletal muscle mass and function decline with aging, and more precipitously after the age 75 y. To help provide insights into biologically relevant mechanisms for preserving muscle mass and function in advanced age, in this study we performed proteomics on skeletal muscle of world class octogenarian track and field athletes in comparison to healthy octogenarian non‐athletes. Methods Muscle cross‐sectional area by MRI and a vastus lateralis muscle biopsy were performed in 15 octogenarian world class track and field athletes (8 of whom were world record holders in their discipline at the time of testing) and 14 non‐athlete age‐ and sex‐matched non‐athlete controls. From these subjects, a portion of muscle from a subset of 12 master athletes (MA mean age 81.19 ± 5.1 y) and 12 non‐athlete controls (NA mean age 80.94 ± 4.5 y) was used for liquid‐chromatography mass spectrometry to generate quantitative tandem mass tag proteomics data. In addition, we measured mtDNA copy number, COX/SDH histochemistry to identify respiratory compromised fibers, and Western blot of mitochondrial inner and outer membrane proteins. Results Muscle cross‐sectional area was higher in MA. Tandem mass spectrometry identified over 6000 proteins, and significant differences in abundance were found between NA controls and MA for more than 800 proteins. A pathway analysis revealed that pathways involved in mitochondria (e.g., TCA cycle, respiratory electron transport, cristae formation, sirtuins) were higher in MA, while proteins in pathways involved in the spliceosome and nuclear pore were downregulated in MA. Finally, 8 mtDNA‐encoded proteins that were included in the analysis were elevated in MA versus NA. These proteomics data are consistent with phenotypic data showing MA have higher mtDNA copy number, fewer respiratory chain compromised muscle fibers, and an increased ratio of ETC subunits (inner mitochondrial membrane proteins) relative to VDAC (outer mitochondrial membrane protein), suggesting an increase in cristae formation. Conclusion Our data underscore that mitochondrial pathways are key to maintaining a high level of physical function in advanced age. With the current study design we cannot determine the degree to which these differences are attributable to the physical activity habits of MA, but it is likely to play a role. Support or Funding Information CIHR (MOP 125986 to RTH) NIA Intramural Research program
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".