Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats
Bibliographic record
Abstract
‘Developmental programming’, as a consequence of suboptimal in-utero and early environments can be associated with metabolic dysfunction in later life, including increased incidence of cardiovascular disease and type 2 diabetes and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with ‘developmental programming’ are also known to be associated with the aging process. We therefore utilized our well-established rat model of low-birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’) in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging) as evidenced by reduced frequency of long telomeres (48.5-8.6kb) and increased frequency of short telomeres (4.2-1.3kb) in vastus-lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA damage repair marker 8-oxoguanine-glycosylase (OGG1) in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria), increased xanthine oxidase (XO), p67phox and Nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Recuperated offspring also demonstrated increased antioxidant defense capacity with increased protein expression of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), Catalase and heme oxygenase-1 (HO1), all of which are known targets of NF-κB and may be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype as evidenced by increased tumor necrosis factor-α (TNFα) and interleukin-1β (IL1β) protein levels. Taken together, we demonstrate for the first time, to our knowledge, an accelerated aging phenotype in skeletal muscle in the context of developmental programming. These findings may pave the way for suitable interventions in at-risk populations.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 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".