Endurance Training Improves Vertebral mtDNA Copy Number In Polymerase Gamma Mutator Mouse Model Of Aging
Bibliographic record
Abstract
Epidemiological studies have shown that aging is associated with osteoporosis and an increased incidence of fractures. A causal role for mtDNA mutagenesis in aging-associated bone loss is supported by recent studies showing that the polymerase gamma (PolG) mutator mouse, harbouring a proofreading-deficient copy of PolG, exhibits a significant reduction in whole-body bone mineral content and density. Furthermore, a recent study has demonstrated that mitochondrial biogenesis contributes to osteoblast differentiation - an important component of the bone modeling unit. Anecdotal evidence from human and rodent studies suggests that endurance training reduces loss of bone mineral density and is recommended to decrease the likelihood of falling, and associated morbidity and mortality. PURPOSE: To investigate the effect of endurance training on mitochondrial gene expression and bone strength decrements in PolG mice. METHODS: At 3 months of age, 24 PolG mice were randomly assigned to a sedentary (SED) or forced-endurance training (END; 15m/min for 45 min, 3x/week for 5 months) group. RESULTS: PolG-SED mice showed a 36% decrease in mitochondrial DNA copy number vs. wild-type (WT) in lumbar vertebrae and no change from WT levels in PolG-END (p<0.05). PolG-END mice showed lower mRNA content of NDUFS1 and FOXO3 (p<0.05) and a trend toward decreased TFAM (p<0.09) compared to PolG-SED. These changes were similar to WT-SED vs. WT-END mice. No difference in COX expression was observed between mice. There was an increase in the expression of BGLAP in PolG-SED vs. WT (p<0.05) and a trend to return to WT-SED levels with exercise (p<0.06). There was a trend toward increased expression of the RANKL/OPG ratio in PolG-END vs. PolG-SED (p<0.06). In the femur, PolG-SED mice exhibited lower biomechanical properties - lower maximal load (33%), maximal energy (39%), stress (33%) and bone area (9%) at the mid-diaphysis (p<0.05) using body weight as a co-variate. PolG-END showed an improvement in all variables (P<0.05), with no change from WT levels. We found no differences in femur length, periosteal and endosteal area at the mid-diaphysis. CONCLUSION: Five months of endurance training rescued the loss of femur strength and positively influenced mitochondrial DNA copy number in lumbar vertebrae of PolG mice. (Funded by CIHR).
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".