Introduction: Understanding Anti-Aging Supplementation
Anti-aging supplementation involves the strategic use of compounds that may slow, halt, or potentially reverse age-related biological processes. This approach targets multiple hallmarks of aging including cellular senescence, mitochondrial dysfunction, oxidative stress, and inflammation. While no supplement can stop aging entirely, evidence suggests that certain nutrients and compounds may support longevity pathways and promote healthier aging. This cheat sheet provides a comprehensive, evidence-based overview of the most promising anti-aging supplements.
Core Anti-Aging Mechanisms & Pathways
| Mechanism | Description | Key Supplements |
|---|---|---|
| Autophagy Activation | Cellular “self-eating” process that removes damaged components | Spermidine, Resveratrol, Fisetin |
| mTOR Regulation | Control of protein synthesis and cell growth pathways | Rapamycin*, Berberine |
| Sirtuins Activation | NAD+-dependent enzymes that regulate cellular health | NMN, NR, Resveratrol |
| AMPK Activation | Energy sensor that regulates metabolism | Berberine, Gynostemma, Hesperidin |
| DNA Repair | Maintenance of genetic integrity | NAC, Nicotinamide, Zinc |
| Senolytic Activity | Removal of senescent (“zombie”) cells | Fisetin, Quercetin with Dasatinib* |
| Telomere Support | Protection of chromosome ends | Astragalus (TA-65), Omega-3s |
| Inflammaging Reduction | Lowering age-related chronic inflammation | Curcumin, Omega-3s, Boswellia |
*Requires prescription in most countries
Foundational Supplements
NAD+ Precursors
Purpose: Boost cellular NAD+ levels that decline with age; support sirtuin activation
| Supplement | Daily Dosage | Evidence Level | Notes |
|---|---|---|---|
| Nicotinamide Mononucleotide (NMN) | 250-1200mg | Moderate | More bioavailable than NR in some studies; take on empty stomach |
| Nicotinamide Riboside (NR) | 250-1000mg | Moderate | Well-studied; clinically demonstrated to increase NAD+ |
| Niacin (B3) | 100-500mg | Low-Moderate | Inexpensive; causes flushing; less direct NAD+ impact than NMN/NR |
Antioxidants & Cellular Protectors
Purpose: Combat oxidative stress and protect cellular components
| Supplement | Daily Dosage | Evidence Level | Notes |
|---|---|---|---|
| Glutathione | 250-1000mg | Moderate | Master antioxidant; liposomal form more bioavailable |
| N-Acetyl Cysteine (NAC) | 600-1800mg | Moderate-High | Glutathione precursor; supports respiratory health |
| Alpha-Lipoic Acid (ALA) | 300-600mg | Moderate | Recycles other antioxidants; glucose regulation |
| CoQ10 (Ubiquinol) | 100-300mg | High | Mitochondrial support; better absorbed with fats |
| PQQ (Pyrroloquinoline Quinone) | 10-20mg | Low-Moderate | Stimulates mitochondrial biogenesis |
| Vitamin C | 500-2000mg | Moderate | Basic antioxidant; collagen synthesis support |
| Vitamin E (Mixed Tocopherols) | 100-400 IU | Moderate | Fat-soluble antioxidant; avoid synthetic forms |
Senolytics & Senomorphics
Purpose: Remove or modify senescent cells that accumulate with age
| Supplement | Daily Dosage | Cycle | Evidence Level | Notes |
|---|---|---|---|---|
| Fisetin | 500-1500mg | 2-3 days per month | Moderate | Most promising natural senolytic; poor bioavailability |
| Quercetin | 500-1000mg | 2-3 days per month | Moderate | Often combined with Dasatinib* for enhanced effect |
| Piperlongumine | 100-200mg | 2-3 days per month | Low | Emerging natural senolytic compound |
| Curcumin | 500-1000mg | Daily | Moderate | Senomorphic (modifies senescent cells); use with black pepper |
| EGCG (Green Tea Extract) | 300-500mg | Daily | Low-Moderate | Senomorphic properties; antioxidant benefits |
*Requires prescription
Specialized Anti-Aging Compounds
Metabolic Regulators
Purpose: Optimize glucose metabolism and energy production
| Supplement | Daily Dosage | Evidence Level | Notes |
|---|---|---|---|
| Berberine | 500-1500mg | High | AMPK activator; “natural metformin”; take with meals |
| Metformin* | 500-2000mg | High | Well-studied drug with multiple aging pathways |
| Resveratrol | 250-500mg | Moderate | Sirtuin activator; take with fat for absorption |
| Spermidine | 1-5mg | Moderate | Activates autophagy; found in wheat germ, aged cheese |
| Gynostemma | 450-800mg | Low-Moderate | AMPK activator; adaptogenic properties |
| Hesperidin | 500-2000mg | Low-Moderate | Citrus flavonoid; AMPK activator; vascular support |
*Requires prescription
Hormone & Peptide Support
Purpose: Support endocrine function that declines with age
| Supplement | Daily Dosage | Evidence Level | Notes |
|---|---|---|---|
| DHEA | 25-50mg | Moderate | Adrenal hormone precursor; monitor levels |
| Pregnenolone | 10-50mg | Low-Moderate | Neurosteroid; cognitive support |
| Melatonin | 0.5-5mg | Moderate-High | Beyond sleep: mitochondrial and DNA protection |
| Vitamin D3 | 2000-5000 IU | High | Hormone rather than vitamin; test levels |
| Growth Hormone Secretagogues | Varies by product | Low-Moderate | CJC-1295, Ipamorelin, etc.; careful monitoring needed |
Cognitive Enhancers with Anti-Aging Effects
Purpose: Protect neural function and support brain health
| Supplement | Daily Dosage | Evidence Level | Notes |
|---|---|---|---|
| Bacopa Monnieri | 300-600mg | Moderate | Neuroprotective; adaptogenic |
| Lion’s Mane Mushroom | 500-3000mg | Moderate | NGF promoter; neurogenesis support |
| Ginkgo Biloba | 120-240mg | Moderate-High | Circulation; mitochondrial support |
| Phosphatidylserine | 100-300mg | Moderate | Cell membrane support; cortisol regulation |
| Acetyl-L-Carnitine | 500-2000mg | Moderate | Mitochondrial support; fat metabolism |
| Magnesium L-Threonate | 1000-2000mg | Moderate | Brain-penetrating form; cognitive support |
Anti-Aging Supplement Stacks by Goal
Longevity Foundation Stack (Daily)
- NMN or NR: 500mg
- CoQ10 (as Ubiquinol): 100-200mg
- Vitamin D3/K2: 2000-5000 IU / 100mcg
- Magnesium: 300-400mg (glycinate, malate, or threonate)
- Omega-3s (EPA/DHA): 1-3g
- B-Complex: 1 serving with methylated forms
Senolytic Pulse Stack (2-3 days monthly)
- Fisetin: 1000-1500mg
- Quercetin: 1000mg
- Piperlongumine: 100mg (optional)
- EGCG: 500mg
- Omega-3s: 2-3g (improved absorption of other compounds)
Metabolic Optimization Stack
- Berberine: 500mg 3x daily with meals
- Resveratrol: 250-500mg
- Alpha-Lipoic Acid: 600mg
- Chromium Picolinate: 200-400mcg
- Cinnamon Extract: 500mg
Mitochondrial Support Stack
- CoQ10 (Ubiquinol): 200-300mg
- PQQ: 10-20mg
- Acetyl-L-Carnitine: 1000-2000mg
- R-Lipoic Acid: 200-300mg
- Magnesium: 300-400mg
- B2 (Riboflavin): 100mg
Inflammation Management Stack
- Curcumin (with black pepper): 1000mg
- Omega-3 (EPA/DHA): 2-3g
- Boswellia Serrata: 300-500mg
- Ginger Extract: 500-1000mg
- Specialized Pro-resolving Mediators: 100-300mg (optional)
Comparison: Natural vs. Pharmaceutical Approaches
| Natural Compound | Pharmaceutical Alternative | Mechanism Overlap | Considerations |
|---|---|---|---|
| Berberine | Metformin* | AMPK activation, mTOR inhibition | Berberine: More GI issues; Metformin: More research |
| Fisetin/Quercetin | Dasatinib*/Quercetin combo | Senolytic activity | Pharmaceuticals stronger but higher side effect profile |
| NMN/NR | No direct equivalent | NAD+ boosting | Natural compounds safer but possibly less effective |
| Spermidine | Rapamycin* (partial overlap) | Autophagy activation | Rapamycin has stronger mTOR inhibition but immunosuppressive |
| Curcumin | NSAIDs* | Anti-inflammatory | Curcumin: gentler, multiple pathways; NSAIDs: stronger, more side effects |
*Requires prescription
Common Challenges & Solutions in Anti-Aging Supplementation
| Challenge | Description | Solution |
|---|---|---|
| Absorption Issues | Many compounds have poor bioavailability | Use liposomal forms, take with fats, add black pepper (piperine) |
| Hormetic Balance | Some anti-aging compounds work through hormesis | Cycle certain supplements (e.g., senolytics) rather than daily use |
| Interaction Concerns | Multiple supplements may interact | Start with foundation stack, add one at a time; consult healthcare provider |
| Cost Barriers | Anti-aging regimens can be expensive | Prioritize most evidence-backed compounds; consider cost per effective dose |
| Testing Limitations | Difficult to measure effectiveness | Use biomarkers (inflammation, glucose, etc.) when possible |
| Dosing Confusion | Optimal amounts unclear in humans | Start with lower doses; follow research-based recommendations |
| Quality Variability | Supplement quality differs dramatically | Choose third-party tested products from reputable manufacturers |
Best Practices for Anti-Aging Supplementation
Timing & Administration
- Take with/without food: Fat-soluble supplements (CoQ10, Vitamin D, Resveratrol) with meals; NMN/NR better on empty stomach
- Circadian considerations: Melatonin before bed; energizing supplements in morning
- Cycling approach: Pulse senolytics monthly; consider cycling other supplements based on research
- Split dosing: Divide larger doses throughout day for better absorption (Berberine, NAC)
Testing & Monitoring
- Baseline biomarkers: Complete blood count, comprehensive metabolic panel, inflammatory markers (hsCRP), hormones, HbA1c, lipid panel
- Specialized tests: DNA methylation testing (biological age), NAD+ levels, telomere length (if available)
- Regular reassessment: Retest every 3-6 months to track changes and adjust protocol
- Subjective tracking: Monitor energy, cognitive function, sleep quality, recovery time
Integration with Lifestyle
- Exercise synergy: Time certain supplements around workout schedule (antioxidants post-workout)
- Fasting windows: Some compounds enhance autophagy during fasting; others break fast
- Sleep optimization: Supplements can’t compensate for poor sleep; prioritize sleep hygiene
- Stress management: Chronic stress negates benefits; include adaptogens if needed
Practical Guidelines for Implementation
Starting a Protocol
- Begin with foundations: Basic vitamins, minerals, omega-3s
- Add one compound at a time: Monitor for 2-3 weeks before adding next
- Prioritize by evidence and need: Address personal health concerns first
- Start with lower doses: Gradually increase to recommended levels
- Consider professional guidance: Consult longevity-focused healthcare provider
Personalization Factors
- Genetic variations: MTHFR, COMT, and other SNPs affect supplement needs
- Age considerations: Different priorities for 30s, 50s, 70+ age groups
- Health conditions: Certain supplements contraindicated with medications/conditions
- Gender differences: Hormonal impacts vary; dosages may need adjustment
- Metabolic status: Insulin sensitivity affects supplement effectiveness
Resources for Further Learning
Scientific Research Databases
- PubMed.gov
- ClinicalTrials.gov
- Longevity Technology Research Portal
- Buck Institute for Research on Aging
Books on Longevity & Supplementation
- “Lifespan” by David Sinclair
- “The Longevity Diet” by Valter Longo
- “The Switch” by James Clement
- “Ageless” by Andrew Steele
Communities & Forums
- r/longevity (Reddit)
- LongeCity Forums
- Life Extension Foundation
- AgingBiotech.info
Testing Resources
- TruDiagnostic (Epigenetic Age)
- InsideTracker (Biomarkers)
- Jinfiniti (NAD+ Testing)
- AgelessRx (Telomere Testing)
Disclaimer: This cheat sheet is for informational purposes only and does not constitute medical advice. Many anti-aging supplements lack conclusive human clinical trials. Always consult with a healthcare provider before starting any supplement regimen, especially if you have medical conditions or take medications.