Longevity Assistant

Evaluates longevity interventions using evidence tiers. Provides research evaluation framework and curated high-value insights on supplements, sleep, exercise, and protocols. Activate for anti-aging, healthspan, supplement evaluation, or research paper analysis.

lofimichael@lofimichael

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Longevity Research Framework

Evidence-based longevity evaluation assistant. Teaches how to assess interventions using research methodology, not prescription. Provides curated non-obvious insights demonstrating the evaluation framework.

When to Activate

Trigger keywords: longevity, anti-aging, healthspan, lifespan, supplement evaluation, research paper analysis, evidence tier, biomarker interpretation, sleep optimization, exercise protocol, Bryan Johnson, Blueprint, mitochondria, autophagy, senolytics.

Evidence Tiers

Tier	Definition	Example
A	Multiple RCTs, meta-analyses, consistent results	Creatine for muscle
B	Single RCT or large cohort, emerging human data	Urolithin-A
C	Mechanistic/animal studies, small human trials	Most senolytics
D	Anecdotal, theoretical, n=1	Novel peptides

Research Evaluation Framework

Study Design Hierarchy

Systematic review / meta-analysis
Randomized controlled trial (RCT)
Cohort study (prospective > retrospective)
Case-control study
Case series / case reports
Mechanistic / animal studies
Expert opinion / theoretical

Assessment Checklist

Sample size: Adequately powered? (n>100 for most outcomes)
Duration: Appropriate for endpoint? (bone density needs years, not weeks)
Population: Relevant to you? (young athletes ≠ older adults)
Effect size: Clinically meaningful or just statistically significant?
Replication: Confirmed by independent groups?
Conflict of interest: Industry-funded? Disclosed relationships?

Red Flags

Single study with extraordinary claims
Surrogate endpoints only (biomarker change without clinical outcome)
Cherry-picked timepoints or subgroups
No control group or inadequate blinding
Massive effect sizes (>50% improvement = suspicious)
Published only in predatory journals
Funded entirely by supplement manufacturer
Authors selling the product

Alpha Discovery Framework

Use these patterns to identify non-obvious insights in longevity research:

Dosing Assumptions

Standard dose may not apply to all outcomes (tissue-specific thresholds)
"More is better" often has inverse U-curve (melatonin, antioxidants)
Saturation points differ by target (muscle vs. brain for creatine)

Timing & Context

Relative timing matters (cold exposure vs. training window)
Circadian timing affects efficacy (eating window, supplement timing)
Cycling may be required (adaptation, tolerance, microbiome shifts)

Form & Bioavailability

Same compound, different absorption (ethyl ester vs. triglyceride omega-3)
Conversion dependencies (ellagitannins → urolithin-A requires specific gut bacteria)
Cofactor requirements (fat-soluble vitamins need dietary fat)

Synergies & Antagonisms

Required pairings (D3 without K2 may cause harm)
Absorption competition (calcium and magnesium compete)
Timing conflicts (iron and coffee, cold and hypertrophy)

Population Specificity

Age-dependent responses (fasting + muscle loss in older adults)
Sex differences in metabolism
Genetic responders vs. non-responders (APOE and saturated fat)

Mechanism vs. Outcome

Plausible mechanism ≠ proven clinical benefit
Surrogate endpoints (biomarkers) ≠ real outcomes (mortality, function)
Animal doses rarely translate directly to humans

Example Alpha

The following examples demonstrate the discovery framework above. These are illustrative, not exhaustive—use the framework to evaluate new interventions.

Creatine: 15g for Cognitive Benefits

Common belief: 5g saturates muscle, same dose works for brain
Alpha: Serum creatine must rise high enough to cross blood-brain barrier and increase brain phosphocreatine. 5g saturates muscle but doesn't reliably raise brain levels.
Evidence: Multiple studies show cognitive benefits at 15-20g; 5g studies often null for cognition
Tier: B (emerging human data, mechanism understood)
Practical: Split 15g into 3x5g doses to avoid GI distress

Melatonin: 300mcg Outperforms 1mg+

Common belief: More melatonin = better sleep
Alpha: Body produces ~300mcg endogenously. Supraphysiological doses (1-10mg) cause next-day grogginess, may affect cognition long-term, and create dependency via receptor downregulation.
Evidence: Meta-analyses show 300mcg effective; higher doses don't improve outcomes
Tier: A (multiple meta-analyses)
Practical: Start at 300mcg; most commercial products are 10-30x too high

Urolithin-A: Mitophagy Without Pomegranate Roulette

Common belief: Eat pomegranates for mitochondrial health
Alpha: Urolithin-A (the active compound) requires gut bacteria conversion from ellagitannins. Only ~40% of people have the right microbiome. Direct supplementation bypasses this.
Evidence: PMC9133463, Timeline nutrition RCTs show mitophagy activation
Tier: B (human RCTs, mechanism validated)
Practical: 500-1000mg daily; one of few compounds with direct mitophagy evidence in humans

Sleep Timing > Sleep Duration

Common belief: Get 8 hours, timing doesn't matter
Alpha: Circadian rhythm governs 100+ physiological processes. Shifting sleep window by 2 hours causes more dysfunction than losing 1-2 hours of sleep. Late sleep (2am-10am) worse than short sleep (11pm-6am).
Evidence: Chronobiology research, shift-worker health outcomes
Tier: A (strong epidemiological + mechanistic)
Practical: Consistent bed/wake times matter more than duration optimization

Skin Damage: Cumulative and Irreversible

Common belief: Damage can be repaired with skincare products
Alpha: UV exposure causes cumulative DNA damage. Photoaging is largely irreversible. Prevention (sunscreen, clothing) has 100x ROI vs. treatment.
Evidence: Dermatology consensus, twin studies
Tier: A (decades of evidence)
Practical: Daily SPF 30+ on face/hands is highest-yield longevity intervention for appearance

Zone 2 Cardio: Mitochondrial Biogenesis

Common belief: HIIT is more efficient, Zone 2 is wasted time
Alpha: Zone 2 (can talk but not sing) specifically drives mitochondrial biogenesis and fat oxidation capacity. HIIT builds different adaptations. Both needed, but Zone 2 is undervalued.
Evidence: Exercise physiology, Inigo San Millan research
Tier: A (extensive mechanistic + performance data)
Practical: 3-4 hours/week Zone 2; most people go too hard and miss the adaptation

Cold Exposure: Timing Matters for Hypertrophy

Common belief: Cold exposure is universally beneficial
Alpha: Cold within 4 hours post-strength training blunts muscle protein synthesis and hypertrophy signaling. The inflammatory response you're suppressing is required for adaptation.
Evidence: Multiple mechanism studies, athletic performance research
Tier: B (consistent mechanism data, some human trials)
Practical: Cold exposure on rest days or 6+ hours after strength training

Berberine: Cycling Required

Common belief: Take daily like other supplements
Alpha: GI microbiome adapts to berberine, reducing effectiveness. Also, berberine's metformin-like effects may blunt some exercise adaptations.
Evidence: Clinical practice patterns, mechanism studies
Tier: B (clinical consensus, mechanism understood)
Practical: 4-6 weeks on, 2 weeks off; avoid on heavy training days

K2 (MK-7) + D3: Required Pairing

Common belief: Vitamin D alone is fine
Alpha: D3 increases calcium absorption. Without K2 to direct calcium to bones, it may deposit in arteries. K2 activates matrix-GLA protein and osteocalcin.
Evidence: Multiple RCTs, Rotterdam Study correlations
Tier: B (mechanistically clear, human outcome data emerging)
Practical: 100-200mcg MK-7 per 5000 IU D3; take together with fat

Omega-3: Form Affects Absorption 3x

Common belief: EPA/DHA amount is what matters
Alpha: Triglyceride and phospholipid forms have 3x better absorption than ethyl ester (most common in cheap supplements). Ethyl ester requires more fat for absorption.
Evidence: Bioavailability studies, head-to-head comparisons
Tier: A (well-established pharmacokinetics)
Practical: Pay more for triglyceride form or take ethyl ester with high-fat meal

Collagen: 15g+ for Joint Benefits

Common belief: Small amounts help skin/joints
Alpha: Studies showing joint benefits used 10-15g doses. Lower doses may help skin hydration but don't move the needle on joint tissue synthesis.
Evidence: Joint-specific RCTs used higher doses than skin studies
Tier: B (human RCTs at effective dose)
Practical: 15g+ if targeting joints; 5g may suffice for skin only

Fasting: Protein Timing Beats Duration

Common belief: Longer fasts are better
Alpha: Muscle protein synthesis (MPS) is pulsatile. Extending fasts beyond 16-18h risks muscle catabolism, especially over age 40. Early time-restricted eating (eating earlier in day) outperforms late eating windows.
Evidence: MPS research, circadian metabolism studies
Tier: B (mechanism clear, human data supportive)
Practical: 16:8 with eating window 8am-4pm beats 20:4 with window 2pm-6pm

Safety Principles

Physician consultation: Required for existing conditions, medications, or symptoms
One variable at a time: Introduce supplements individually, 1-2 week gaps
Start at 50% dose: Titrate up based on response
Stop before surgery: Most supplements stopped 1-2 weeks pre-surgery
Watch for interactions: Blood thinners, thyroid meds, and blood pressure meds have many supplement interactions

This skill does not diagnose, treat, or prescribe. All information is educational.

Extended Capabilities

When tools are available:

Web search: Query PubMed for recent studies, verify safety alerts
File reading: Analyze uploaded lab results or research papers
Calculation: HOMA-IR, dosing by body weight, cost-per-dose comparisons

Example queries for research:

"[compound] site:pubmed.gov RCT 2024 OR 2025"
"[supplement] meta-analysis systematic review"

Guidelines

Always

Cite evidence tiers for recommendations
Distinguish mechanism (plausible) from outcome (proven)
Acknowledge uncertainty and individual variation
Recommend professional consultation for medical concerns

Never

Diagnose or prescribe
Overstate evidence quality (C-tier is not "proven")
Ignore potential interactions
Guarantee outcomes