Protocol Brief
The research, distilled.
Weekly PMID-cited research drops tied to live library updates — every headline links straight to the module it moves.
Weekly research summaries tied to library updates — 25 issues in rotation (19 synced from Research Intel). Every headline links to actionable modules.
What this is
PMID-curated research digest — weekly issues synced from Research Intel with links to hallmarks, compounds, and stacks.
Why it matters
Headlines without protocol context waste time. Every Brief issue maps studies to actionable TNiC modules.
What to do next
Read the latest issue, follow protocol links, then subscribe for RSS/JSON feeds or email delivery.
Six evidence comparison routes (NMN vs NR, NRF2 vs Mito, and more) and brand-agnostic buyer guides now live on every compound module. Decision tools beat catalog browsing.
Takeaway
Before buying, run compare → buyer guide → labs baseline in that order.
Igarashi 2022 and Liao 2021 RCTs confirm 250 mg/day raises blood NAD+ metabolites with functional signals over 12 weeks. TNiC standardizes on this dose before titration.
Takeaway
Retest NAD+ at week 4 — not week 12. Flat at 4 weeks → audit product COA first.
Kumar trials show dual-precursor GlyNAC restores erythrocyte glutathione and improves mitochondrial markers in older adults. Liposomal GSH lacks equivalent longevity-trial depth.
Takeaway
Schedule week-12 and week-24 GSH draws — single baseline proves nothing.
NRF2 activation requires glucoraphanin conversion via myrosinase. Broccoli powder without quantified GR + enzyme fails the buyer guide — regardless of marketing.
Takeaway
Pair sulforaphane AM with GlyNAC — substrate before gene switch.
Harrison 2009 and replications establish rapamycin as the top pharmacological lifespan extension in mice. Human use remains off-label Rx with immunosuppression monitoring — research chemicals are never acceptable.
Takeaway
OTC stacks complement — never substitute — physician-managed rapamycin.
All hallmark MDX modules now at template standard with decision trees, compare blocks, and monitoring tie-ins. Homepage tiles route symptoms to mechanisms.
Takeaway
Start at the hallmark that matches your labs — not the supplement you saw advertised.
Muscle-targeted FGF21 delivery increased median lifespan and improved healthspan markers in male mice.
Takeaway
PubMed 42231578 — use protocol links above before changing your stack.
Ca-AKG supplementation extended lifespan 12–14% by modulating energy metabolism and epigenetic regulation.
Takeaway
PubMed 32877690 — use protocol links above before changing your stack.
Targeting biological aging yields 10× greater healthy lifespan gains than curing individual diseases.
Takeaway
PubMed 24101058 — use protocol links above before changing your stack.
First clinical evidence showing oral dasatinib+quercetin reduces senescent cell burden and SASP cytokine levels in adipose tissue of adults with idiopathic pulmonary fibrosis — establishing senolytics as a viable human intervention strategy.
Takeaway
PubMed 31542391 — use protocol links above before changing your stack.
12-week Ca-AKG supplementation reduced biological age by a mean 8.1 years as measured by the Horvath epigenetic clock in middle-aged adults, with concurrent improvements in musculoskeletal and immune function composites.
Takeaway
PubMed 34847066 — use protocol links above before changing your stack.
Adults averaging under 6 hours per night accrued 1.8 additional years of epigenetic aging per chronological year vs. 7–9 hour sleepers — an effect size larger than most supplement interventions and establishing sleep as a first-order longevity variable.
Takeaway
PubMed 27702440 — use protocol links above before changing your stack.
Landmark Science study showed 10-week NMN supplementation increased insulin-stimulated glucose disposal in skeletal muscle of postmenopausal women with prediabetes — establishing a direct mechanistic link between NAD+ restoration and human metabolic aging.
Takeaway
PubMed 33888596 — use protocol links above before changing your stack.
30-day resveratrol supplementation in obese men activated SIRT1 and AMPK, improved mitochondrial biogenesis, reduced inflammatory markers including IL-6, and lowered metabolic risk factors — closely mimicking the effects of caloric restriction without dietary change.
Takeaway
PubMed 22055504 — use protocol links above before changing your stack.
Mayo Clinic pilot trial using intermittent fisetin dosing significantly reduced circulating senescent cell burden (p16INK4A, p21) and improved composite physical function scores in older adults — providing the first human evidence that a senolytic flavonoid can measurably reduce the SASP-driving zombie-cell load.
Takeaway
PubMed 30279143 — use protocol links above before changing your stack.
Landmark multi-species Science study found taurine levels decline 80% with age in humans, mice, and monkeys. Taurine supplementation increased median lifespan 10–12% in mice, with improvements across immune function, bone density, muscle strength, insulin sensitivity, and epigenetic clocks — making it one of the broadest single-compound longevity interventions documented to date.
Takeaway
PubMed 37289866 — use protocol links above before changing your stack.
Randomized placebo-controlled trial in older adults showed that oral urolithin A (a gut-microbiome metabolite of pomegranate ellagitannins) significantly increased skeletal muscle mitochondrial gene expression and activated mitophagy — the selective recycling of damaged mitochondria. This is the first human clinical proof that a gut-derived compound can stimulate mitophagy in the muscle of aging adults.
Takeaway
PubMed 31230029 — use protocol links above before changing your stack.
Three-month randomized controlled trial in adults aged 60–80 with subjective cognitive decline showed that spermidine supplementation (from wheat germ extract) significantly improved memory performance versus placebo. Spermidine is a polyamine that activates autophagy — the cellular recycling pathway that declines with age and is implicated in neurodegenerative disease progression.
Takeaway
PubMed 29563638 — use protocol links above before changing your stack.
Randomized clinical trial showed berberine (500 mg three times daily) reduced fasting blood glucose by 20% and HbA1c by 2.0% in patients with type 2 diabetes — outcomes comparable to metformin at equivalent dose. Berberine activates AMPK, the cellular energy sensor that also inhibits mTOR, mimicking some effects of caloric restriction and placing it in the AMPK/longevity pathway alongside metformin and resveratrol.
Takeaway
PubMed 18396172 — use protocol links above before changing your stack.
Double-blind Phase 2 randomized trial in adults ≥65 showed 500mg/day Mitopure (standardized urolithin A) over 4 months significantly improved mitochondrial gene expression, aerobic endurance (6-minute walk test), and muscle strength (hand grip, leg press) versus placebo — with full safety and tolerability confirmed. This is the first Phase 2 human proof that targeting mitophagy pharmacologically translates to functional muscle improvements in aging adults.
Takeaway
PubMed 35391504 — use protocol links above before changing your stack.
Landmark REDUCE-IT trial (n=8,179) showed icosapentaenoic acid (Vascepa, 4g/day) reduced major adverse cardiovascular events by 25% relative risk and 5% absolute risk versus placebo in patients with elevated triglycerides on statin therapy — the largest absolute cardiovascular risk reduction ever demonstrated for a nutraceutical agent. The trial established EPA as a distinct anti-inflammatory cardioprotective agent through specialized pro-resolving mediator (SPM) mechanisms rather than lipid-lowering alone.
Takeaway
PubMed 30145934 — use protocol links above before changing your stack.
Systematic review and meta-analysis of 17 randomized controlled trials found CoQ10 supplementation significantly reduced hs-CRP (by 0.35 mg/L), IL-6 (by 0.50 pg/mL), and TNF-α compared to placebo — establishing anti-inflammatory effects across diverse patient populations. CoQ10 biosynthesis declines ~50% with aging and is further suppressed by statin use, identifying supplementation as a targeted intervention for the inflammaging driven by mitochondrial dysfunction.
Takeaway
PubMed 26267690 — use protocol links above before changing your stack.
Stanford 17-week crossover RCT (n=36) found that daily consumption of 6 servings of fermented foods (yogurt, kimchi, kefir, kombucha) increased microbiome diversity by 26% and reduced 19 inflammatory proteins — including IL-6, IL-12, and CXCL10 — more effectively than a matched high-fiber diet, which increased microbiome function but not diversity. The study resolves a longstanding debate: for anti-inflammatory gut remodeling, fermented foods outperform fiber in the short term.
Takeaway
PubMed 34256014 — use protocol links above before changing your stack.
Mayo Clinic open-label pilot (n=14 adults, mean age 72) using intermittent high-dose fisetin (20 mg/kg/day × 2 consecutive days) found significant reductions in circulating p16INK4A and p21 senescence biomarkers in blood and adipose tissue biopsies — alongside improved composite physical function on SPPB assessment. This represented the first human clinical evidence that a dietary-sourced flavonoid can measurably reduce senescent cell burden in older adults, validating the senolytic pharmacology established in rodent models.
Takeaway
PubMed 30279143 — use protocol links above before changing your stack.
The Targeting Aging with Metformin (TAME) trial — the first FDA-approved clinical trial targeting biological aging itself (rather than a disease) — enrolled 3,000 adults across 14 US sites. Primary endpoint is delay of the composite aging outcome (new-onset diabetes, cancer, dementia, or death). Rationale: metformin activates AMPK and inhibits Complex I, mimicking caloric restriction. Observational data show diabetics on metformin outlive age-matched non-diabetic controls not on metformin — an extraordinary signal establishing aging itself as a modifiable pharmaceutical target.
Takeaway
PubMed 32910831 — use protocol links above before changing your stack.