REVERSING AGING BY IMPROVING ENERGETICS, STRENGTH, COGNITION AND INFLAMMATION IN OLDER HUMANS: ROLE OF GLUTATHIONE
Bibliographic record
Abstract
Aging in older humans is associated with impaired mitochondrial fatty-acid oxidation (MFO), muscle weakness, cognitive decline and inflammation, but contributing mechanisms are not well understood and effective interventions are lacking. We proposed a unifying hypothesis that deficiency of the endogenous antioxidant protein Glutathione predisposes to all of these defects which are reversible on correcting Glutathione deficiency. To test our hypothesis, we conducted a 36-week open label clinical trial (NCT02348762) in 8 older humans (73.8 ± 1y) studied before and after 24-weeks of supplementation with N-acetylcysteine and Glycine (NAC-Gly, as Glutathione precursor amino-acids), and again 12-weeks after stopping supplements to determine washout changes. 8 young humans (25.8 ± 1y) served as controls, and were not supplemented. Study measures were intracellular Glutathione, fasted MFO (calorimetry), physical function (gait-speed, grip-strength, chair-rise and 6-minute walk tests), cognition (MoCA, Montreal Cognitive-Assessment; trail-making tests; verbal-fluency test; symbol-digital modalities test), plasma oxidative-stress (F2-isoprostanes), inflammation (Interleukein-6; Tumor Necrosis Factor alpha; C-reactive Protein) and body composition (DEXA-scan). Compared to young-controls, older humans had significantly (P<0.05 to P<0.01) impaired MFO, physical and cognitive decline, and higher inflammation and body fat. After 24-weeks of supplementation outcome measures improved significantly (P<0.05 to P<0.01), with complete normalization of fMFO (P<0.001), gait-speed (strength, P<0.001) and MoCA (cognition, P<0.01) to young controls. Accrued benefits declined on stopping supplementation. These novel discoveries provide a proof-of-concept for the exciting possibility that supplementing NAC-Gly in older humans could offer a novel nutritional approach to reverse age-related abnormalities in mitochondrial energetics, physical function, cognition, inflammation and body composition, and thereby ‘reverse aging’.
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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 | 0.000 | 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".