Elevated biomarkers of neural injury in older adults following head-down bed rest: links to cardio-postural deconditioning with spaceflight and aging
Bibliographic record
Abstract
Introduction: Prolonged physical inactivity with bed rest or spaceflight is associated with cardiovascular and neuromuscular deconditioning; however, its impact on neural integrity of cardio-postural reflexes and possible mitigation with exercise has not been examined. We assessed the association between the physiological deconditioning of bed rest immobilization with neural injury markers and the effects of 60-75 min of daily exercise. Methods: Data were collected as part of a randomized clinical trial (clinicaltrials.gov identifier: NCT04964999) at the McGill University Medical Centre. Twenty-two 55- to 65-year-old healthy volunteers gave informed consent and took part. Within sex, participants were randomly assigned to exercise (60- to 75-min daily) or control (inactive) groups and spent 14 days in continuous 6° head-down tilt. Neural injury [neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau (t-Tau), myelin basic protein (MBP), brain-derived neurotrophic factor (BDNF), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1)], as well as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and insulin-like growth factor 1 (IGF-1) biomarkers were measured before, during, and after bed rest. The false discovery rate with Huber M-estimation was used to correlate changes in biomarkers with cardiovascular and muscular function changes over bed rest. Results: Bed rest elevated NfL, GFAP, TNF-α, and IL-6 in all participants and reduced IGF-1 in females only. With standing, changes in heart rate, blood pressure, and lower limb muscle motoneuron activity correlated with changes in TNF-α and BDNF. Baroreflex control, leg muscle maximal voluntary contraction, and postural sway are correlated with GFAP and NfL. Exercise participants had fewer interactions than control participants, but significant correlations still existed, with both groups exhibiting similar reductions in orthostatic tolerance. Discussion: An hour of daily exercise in older persons otherwise immobilized for 2 weeks did not abate bed rest-induced increases in serum signatures of neural injury or pro-inflammatory markers. Exercise reduced the number of physiological interactions of biomarkers, but significant cardio-postural correlations remained with no protection against post-bed rest orthostatic intolerance. The identification of associations of inflammatory and neural injury biomarkers with changes in cardio-postural physiology and exercise points to biotherapeutic opportunities and improved exercise interventions for astronauts and individuals in bed rest. Clinical trial registration: https://www.clinicaltrials.gov/search?cond=NCT04964999, identifier: NCT04964999.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| 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".