Selected publication milestones, not an exhaustive history or discovery priority claim.
2014 — Older diabetic observational survival associations vary with frailty and active-drug comparator. Original PMID25506599.
2016 — NR human pharmacokinetics establish exposure rather than older clinical benefit. Original PMID27721479.
2018 — Short NR crossover demonstrates circulating NAD augmentation and bounded vascular leads. Original PMID29599478.
2018 — Metformin older-tissue pathways supply physiological rather than lifespan evidence. Original PMID29383869.
2019 — Metformin/exercise interaction shows blunted fitness/metabolic adaptation in older adults. Original PMID30548390.
2019 — MASTERS separates blunted muscle growth from a nonsignificant strength trend. Original PMID31557380.
2019 — Aged human muscle metabolome responds to NR without changed bioenergetics. Original PMID31412242.
2020 — Single-dose NMN feasibility precedes chronic physical-outcome testing. Original PMID31685720.
2021 — Prediabetic-women NMN clamp physiology establishes its own endpoint and population. Original PMID33888596.
2021 — Young/middle-aged runner threshold effects coexist with peak-capacity nulls. Original PMID34238308.
2022 — Twelve-week older timing trial yields interactions and within-arm improvements, not clear pairwise efficacy. Original PMID35215405.
2022 — Older-men gait leads require supplier-switch, sample and multiplicity interpretation. Original PMID35927255.
2022 — NR/pterostilbene induced-muscle-injury trial gives a direct recovery null. Original PMID35998039.
2023 — Middle-aged NMN walking/exposure dose results remain separate from ≥60 efficacy. Original PMID36482258.
2023 — Older-diabetic impaired-function NMN primary tests are null at24weeks. Original PMID36443648.
2023 — MIB626 changes NAD and selected cardiometabolic measures with physical-performance nulls. Original PMID36740954.
2023 — Mouse isotope tracing challenges assumptions of widespread intact NMN uptake. Original PMID37446292.
2024 — A real secondary gait-time signal occurs alongside stepping, grip and SPPB nulls in older adults. Original PMID38789831.
2024 — NR-PAD supplies a genuine different-molecule walking positive with specific statistical limits. Original PMID38871717.
2024 — Metformin knee-OA adjunct trial retains a distinct pain/function positive. Original PMID38869746.
2025 — MET-PREVENT tests frail-older function directly and finds no gait benefit with tolerability concerns. Original PMID40147475.
2026 — Newer NR-MCI primary cognition remains null despite NAD rise. Original PMID42478598.
2026 — PERMET establishes a direct metformin-PAD walking null. Original PMID41205146.
2026 — DEMFOS distinguishes lifestyle efficacy from absent added metformin function. Original PMID42532077.
2026 — METFORAGING provides a longer biomarker primary null rather than human longevity evidence. Original PMID42023167.
Adequate prespecified objective-function replication and clinically interpretable effect size.
Independent verification of exact formulations, target-tissue NAD and necessary functional mediator.
Prospective baseline disease/function/sex and dose interactions rather than cross-trial subgroup narratives.
Complete missing-data, allocation-error and multiplicity audits across older trials.
Longer clinical functional trajectory, disease incidence and survival rather than biological-age algorithms.
Long-term safety and drug/exercise interactions with molecule-specific attribution.
Randomize baseline-defined ≥60 adults to exact NMN formulation and matched placebo for24weeks, with gait/strength/capacity prespecified as primary or multiplicity-controlled co-primary, meaningful effect size and complete assignment-based analysis. Include prospectively defined healthy and impaired-function/diabetes strata with interaction testing, independent blinded assessors and proper allocation auditing. Measure muscle NAD and pathway controls separately, and extend functional/disease follow-up.