Overexpression of human OGG1 improves skeletal muscle endurance in mice
Bibliographic record
Abstract
8‐oxoguanine glycosylase 1 (OGG1) is a DNA glycosylase that catalyzes the excision of oxidized guanines as part of the base excision repair (BER) DNA repair pathway. While OGG1 has been studied extensively for its role in tumor prevention and neurodegeneration, recent studies have indicated a novel role for this enzyme in maintaining metabolic health. In particular, deletion of OGG1 increased propensity to diet‐ and age‐induced obesity, as well as impaired skeletal muscle dysfunction. In contrast, overexpression of human OGG1 (hOGG1) significantly protected mice from diet‐induced obesity and related metabolic sequelae. Unbiased transcriptomics studies using mice constitutively overexpression OGG1 ( Ogg1 ‐transgenic ‐ Ogg1 Tg ) revealed significant transcriptional changes in skeletal muscle of these mice. Among the most highly induced genes, expression of the myokine fibroblast growth factor‐21(FGF21) was elevated by 9.9 fold in RNA‐Seq analyses. qPCR analysis further confirmed these changes in skeletal muscle without any alterations in the hepatic or cardiac expression of Fgf21 . Commensurate with gene expression changes, plasma FGF21 was elevated by 11.2 fold in Ogg1 Tg mice relative to WT controls. Conversely, Fgf21 gene expression in skeletal muscle and plasma FGF21 levels were decreased by 25 and 29% respectively in Ogg1 ‐/‐ mice. Consistent with increased FGF21 activity, phosphorylation of AMPK and its target acetyl CoA carboxylase (ACC), and Ser/Thr phosphorylation of Akt were significantly increased in Ogg1 Tg muscle. FGF21 is known to increase expression of PGC‐1α protein. Consistently, Ogg1 Tg mice had a 1.6 fold increase in PGC‐1α protein. Given these alterations, we asked if markers of muscle health such as endurance would be altered in Ogg1 Tg mice. Interestingly, Ogg1 Tg mice displayed a 3.4 fold increase in running capacity, consistent with improved skeletal muscle health in these animals. This improvement in exercise capacity was evident in both young and aged mice and have important implications to the management of age‐related declines in muscle health and DNA repair capacity.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".