Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction
Bibliographic record
Abstract
Aging is associated with increased circulating interleukin-6 (IL-6) and a reduced myogenic capacity, marked by reduced muscle stem cell [satellite cell (SC)] activity. Although IL-6 is important for normal SC function, it is unclear whether elevated IL-6 associated with aging alters SC function. We hypothesized that mild chronically elevated IL-6 would be associated with a blunted SC response through altered IL-6 signaling and elevated suppressor of cytokine signaling-3 (SOCS3) in the elderly. Nine healthy older adult men (OA; 69.6 ± 3.9 yr) and 9 young male controls (YC; 21. 3 ± 3.1 yr) completed 4 sets of 10 repetitions of unilateral leg press and knee extension (75% of 1-RM). Muscle biopsies and blood were obtained before and 3, 24, and 48 h after exercise. Basal SC number was 33% lower in OA vs. YC, and the response was blunted in OA. IL-6(+)/Pax7(+) cells demonstrated a divergent response in OA, with YC increasing to 69% at 3 h and peaking at 24 h (72%), while IL-6(+)/Pax7(+) cells were not increased until 48 h in OA (61%). Type II fiber-associated phosphorylated signal transducer and activator of transcription (pSTAT3)(+)/Pax7(+) cells demonstrated a similar delay in OA, not increasing until 48 h (vs. 3 h in YC). SOCS3 protein was 86% higher in OA. These data demonstrate an age-related impairment in normal SC function that appears to be influenced by SOCS3 protein and delayed induction of IL-6 and pSTAT3 in the SCs of OA. Collectively, these data suggest dysregulated IL-6 signaling as a consequence of aging contributes to the blunted muscle stem cell response.
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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 | 0.000 | 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) | 0.001 | 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".