Long‐term caloric restriction increases apoptosis and decreases cell stress response, despite an elevation in antioxidant enzyme capacity in the skeletal muscle of the Cu/Zn‐SOD mutant G93A mouse, an animal model of ALS
Bibliographic record
Abstract
Despite its life‐extending properties, long‐term caloric restriction (CR) hastens clinical onset and shortens life span in the G93A mouse, an animal model of ALS (Hamadeh et al , 2005; Hamadeh and Tarnopolsky, 2005). We previously reported that CR increased lipid peroxidation (MDA) in this model (Patel et al , 2007). We hypothesized that CR would increase apoptosis and decrease cell stress response, with an incomplete compensatory upregulation of antioxidant enzymes. We investigated the effect of long‐term CR on the protein content of antioxidant enzymes (GPx1, GR), and markers of cell stress response (Hsp70) and apoptosis (Bax, caspase 9, cleaved caspase 9) in 99 d quadriceps of G93A mice. Starting at age 40 d, 27 mice were divided into ad libitum (AL, 14; 7 males) or CR (13; 7 males; 60% of AL). GPx1 increased in CR vs. AL mice (37%, P = 0.019) and in CR vs. AL females (56%, P = 0.012), with no change in GR. GPx1/GR was higher in CR vs. AL females only (88%, P = 0.013). Hsp70 was lower in CR vs. AL mice (62%, P = 0.002) and in males vs. females (37%, P = 0.030). Bax was higher in CR vs. AL mice (41%, P = 0.027) and in CR vs. AL females (52%, P = 0.048). Bax/Bcl‐2 was elevated in CR vs. AL mice (68%, P = 0.040) and in CR vs. AL females (2.3‐fold, P = 0.029). There were no differences in caspases. We conclude that CR increases apoptosis in the G93A mouse due to impairment in cell stress response and an incomplete compensatory upregulation of antioxidant enzymes. Grant Funding Source Hamilton Health Sciences Foundation, NSERC, Faculty of Health‐York University
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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) | 0.000 | 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".