2026-07-11

2026-07-11 — ad-hoc daily log

[2026-07-11] ingest + correction | taurine aging evidence adjudication

Added study pages: singh-2023-taurine-deficiency-aging, fernandez-2025-taurine-aging-biomarker, marcangeli-2025-taurine-aging-humans, kim-2026-taurine-frailty, sharma-2025-taurine-leukaemogenesis, and zhang-2025-taurine-dementia.

Updated: molecules/compounds/taurine.md through a 2026-07-11 literature search and primary-source adjudication.

Corrections:

• Singh 2023 did not supplement humans; its human arms were observational. The reported 2,045-CpG and H3K9me3/H3K27me3 experiments were mouse-only, tissue-specific, and not an epigenetic-clock analysis.
• Corrected a prior Singh macaque extraction error: lipid peroxide decreased approximately 11%, not 31% (8-OH-dG ~36%; protein carbonyl ~20%).
• Fernandez 2025 is a challenge to the universal biomarker/deficit premise, not a failed replication of Singh’s intervention.
• Marcangeli 2025 adds an independent human null for age, function, metabolic, inflammatory, and ex-vivo muscle-mitochondrial associations; Kim 2026 adds non-monotonic frailty stratification.
• Sharma 2025 did directly test oral taurine: 10 mg/mL drinking water accelerated established transplanted blast-crisis CML in mice. The page now distinguishes strong preclinical progression evidence from absent cancer-initiation/general-population evidence and removes the systemic-mTOR overgeneralization.
• Wang/Oudit 2026 pooled taurine trials in non-PASC conditions; it did not demonstrate taurine treatment efficacy in long COVID. The separate PASC taurine-deficit association is retained.
• Zhang 2025 Malmö (n=27,786) adds a large prospective null for dietary/plasma taurine and dementia, weakening the earlier suggestive Framingham signal.

Trial status: TauAge NCT06613542 (n=90; 4 g/day for six months; proteomic and DNA-methylation biological-age outcomes) completed 2025-11-13 with no results posted as of 2026-07-11.

Gaps: independent mouse-lifespan replication; published TauAge results; longer human trials with baseline-taurine stratification and functional/clinical outcomes.

[2026-07-11] ingest | L-theanine cognition and affect meta-analysis (user-prompted)

Trigger: user supplied Gerolymos et al. 2026, Molecular Psychiatry, doi:10.1038/s41380-026-03727-9.

Added:

• studies/gerolymos-2026-l-theanine-meta-analysis.md — 31 placebo-controlled oral RCTs, n=1,168. Preserves the strongest acute choice-reaction-time result, the bias-sensitive stress estimate, null fatigue and mostly-null anxiety results, and the sensitivity-only depressive-symptom signal.
• molecules/compounds/l-theanine.md — canonical identity (PubChem 439378; ChEMBL CHEMBL3039113; DrugBank DB12444), evidence synthesis, aging-scope limits, and ClinicalTrials.gov active-record count.

Propagation: linked existing plain-text L-theanine mentions on molecules/compounds/egcg.md to the new canonical compound page. No aging hallmark, target, or mechanism was assigned because the supplied meta-analysis tests neurobehavioral efficacy rather than aging biology or molecular target engagement.

Verification status: both new atomic pages remain verified: false. The official publisher abstract, figures, supplementary material, PubMed metadata (PMID 42410082), and canonical compound databases were checked, but the subscription-only article could not be read end to end. Quantitative claims are restricted to publisher materials and tagged #gap/no-fulltext-access.

Clinical-trial query: ClinicalTrials.gov v2, queried 2026-07-11 with L-theanine and theanine; 8 unique RECRUITING or ACTIVE_NOT_RECRUITING records. Most are combination/co-intervention studies, not isolated L-theanine trials.

[2026-07-11] ingest + verify | ME/CFS DTI-ALPS and glymphatic-interpretation audit

Trigger: user requested Thapaliya et al. 2026, Frontiers in Neuroscience, doi:10.3389/fnins.2026.1875420.

Added:

• studies/thapaliya-2026-me-cfs-dti-alps.md — verified full-text extraction of the single-center cross-sectional study (61 enrolled; 58 analyzed: 31 ME/CFS, 27 healthy controls).
• methods/dti-alps.md — verified method page covering the directional-diffusivity formula, acquisition/ROI/QC dependencies, crossing-fiber and white-matter-geometry confounds, and evidence-weight rules.

Main result: bilateral DTI-ALPS was lower in ME/CFS (1.44 ± 0.086 vs 1.51 ± 0.11; raw p=0.014, p-FDR=0.028). The right-sided group comparison was significant, but the left-sided comparison and direct between-group asymmetry comparison were null. Within cases, the bilateral index correlated with single-item sleep-disturbance (r=−0.47) and impaired-concentration (r=−0.43) ratings; the separate WHODAS cognition score and fatigue were among the null associations.

Method adjudication: DTI-ALPS was retained as a local, protocol-dependent periventricular directional-diffusivity metric, not a direct measurement of waste clearance. Mossige et al. 2026 (Radiology, doi:10.1148/radiol.252070; n=56) found limited correspondence with intrathecal contrast-enhanced MRI and no 48-hour tracer-dynamics association. The ME/CFS result is therefore hypothesis-generating and does not demonstrate glymphatic failure, waste accumulation, neuroinflammation, accelerated aging, or causal direction with sleep/cognition.

Source defects: Table 3 drops decimal places from two standard deviations, contains an impossible reversed confidence interval, reports a context-dependent 1.40/1.41 right-index discrepancy, and labels values as Cohen’s d that are incompatible with displayed independent-group means/SDs. The wiki uses the values corroborated by the abstract/results text and does not propagate the unusable effect-size column.

Propagation: updated interventions/lifestyle/sleep.md, tissues/brain.md, and acronyms.md. The paper did not test a sleep intervention or aging trajectory; no treatment recommendation or hallmark edge was added.

Gap: independent preregistered replication with objective sleep/cognitive measures, component diffusivities, white-matter/ventricular-geometry covariates, and an orthogonal fluid-clearance assay. gap/needs-replication

[2026-07-11] ingest + verify | glymphatic-system process and foundational refresh

Trigger: user requested a canonical glymphatic-system page seeded and validated with missing foundational and current research.

Added and independently verified:

• processes/glymphatic-system.md — canonical type: process page, not an organ-system MOC. It separates periarterial influx, parenchymal exchange/redistribution, net efflux, and downstream meningeal-lymphatic drainage; distinguishes perivascular flow from diffusion/dispersion in neuropil; and grades human measurements by what they actually measure.
• studies/xie-2013-sleep-glymphatic-clearance.md — full extraction of the foundational sleep-state mouse study. The frequently quoted extracellular-space result is 14.1% awake versus 23.4% asleep: +9.3 percentage points, approximately +66% relative, not +60 percentage points. The largest terminal clearance cohort was n=77, distributed across time points.
• studies/kress-2014-glymphatic-aging.md — canonical natural-aging mouse study with assay-specific denominators. Old mice showed a reported 40% relative impairment of injected amyloid-β clearance, 27% lower penetrating-arteriole pulsatility, and reduced perivascular AQP4 polarization; these parallel findings do not establish causal ordering.

Foundational/current literature integrated: Iliff 2012; Smith 2017 versus the five-center Mestre 2018 AQP4 re-test; Holter/Mestre compartment-specific transport evidence; Louveau/Aspelund/Absinta meningeal-lymphatic anatomy; Hablitz circadian and anesthesia work; Fultz 2019 human CSF/hemodynamic coupling; Miao 2024 plus its source-data correction and unresolved 2025 Matters Arising/reply; Hauglund 2025 norepinephrine-linked vasomotion; Väyrynen and Dagum 2026 human studies; and the verified Mossige/Thapaliya DTI-ALPS evidence.

Verifier corrections: corrected a Dreha-Kulaczewski DOI and restricted that result to ventricular CSF displacement; corrected the phase relationship among Hablitz 2020 influx/brain-to-blood clearance/lymph-node filling; separated Hauglund’s zolpidem fluorescent-influx experiment from its radiotracer-clearance experiment; added Absinta’s human/marmoset anatomy; and removed unsupported broad disease/intervention claims. No retraction was found; relevant Louveau and Miao corrections are represented.

Scientific adjudication: sleep-linked CSF influx, vascular/CSF oscillations, and state-dependent fluid dynamics are supported. Whether sleep increases net parenchymal efflux of endogenous solutes remains actively contested. AQP4 facilitates transport in multiple laboratories, but its mechanism and effect size are not settled. DTI-ALPS, visible perivascular spaces, CSF oscillations, mobility measures, and tracer clearance are not interchangeable.

Propagation: updated interventions/lifestyle/sleep.md, tissues/brain.md, cell-types/astrocytes.md, cell-types/neurons.md, organ-systems/nervous-system.md, methods/dti-alps.md, and acronyms.md. Removed stale claims that the Xie full text was unavailable, that slow-wave sleep is a validated peak-clearance intervention, or that enhancing glymphatic clearance is clinically validated.

Open gaps: a safe non-invasive human reference standard; longitudinal healthy-aging tracer data; causal AQP4-polarization intervention evidence; matched experiments that measure influx and efflux separately; and randomized trials showing that changing a validated transport measure improves cognition or aging outcomes. gap/contradictory-evidence gap/needs-human-replication