Top 8 Anti-Aging Compounds Identified in 2024 Cell Metabolism Review

A comprehensive review published in Cell Metabolism in late 2024 systematically evaluated the scientific evidence for various anti-aging compounds, identifying 8 molecules with the strongest data supporting their longevity-promoting effects. This landmark analysis provides a roadmap for evidence-based anti-aging supplementation.

The Review Methodology

The research team evaluated over 500 compounds that have been proposed to have anti-aging effects. Each was assessed based on:

• Mechanistic understanding (how it works at the molecular level)
• Preclinical evidence (animal studies showing lifespan or healthspan extension)
• Human clinical data (safety and efficacy in humans)
• Reproducibility (consistent results across multiple independent studies)

The Top 8 Anti-Aging Compounds

1. NAD+ Precursors (NMN and NR)

Evidence Rating: A

NAD+ precursors topped the list due to their well-characterized mechanism and growing human evidence. These compounds boost cellular NAD+ levels, which decline significantly with age and are essential for hundreds of metabolic processes.

• Mechanism: Restore NAD+ levels, activate sirtuins, enhance mitochondrial function
• Key Evidence: Multiple human trials showing improved metabolic markers, muscle function, and vascular health
• Typical Dose: NMN 250-500mg/day; NR 300-600mg/day

2. Rapamycin and Rapalogs

Evidence Rating: A

Rapamycin remains the gold standard for lifespan extension in laboratory animals. While its use in healthy humans requires careful consideration due to immunosuppressive effects, rapalogs (rapamycin analogs) with improved safety profiles are in development.

• Mechanism: mTOR inhibition, autophagy activation, immune modulation
• Key Evidence: Extends lifespan in every animal model tested; human trials for immune and cardiac function
• Status: Requires prescription; best used under medical supervision

3. Metformin

Evidence Rating: A-

This diabetes medication has emerged as a leading anti-aging candidate based on epidemiological data and mechanistic studies. The TAME trial (see our separate article) is providing crucial human data.

• Mechanism: AMPK activation, mitochondrial complex I inhibition, reduced inflammation
• Key Evidence: Diabetics on metformin have lower all-cause mortality than non-diabetics
• Typical Dose: 500-2000mg/day (requires prescription)

4. Spermidine

Evidence Rating: B+

This natural polyamine has gained significant attention for its autophagy-inducing properties and favorable safety profile. Recent human trials have shown cognitive benefits in aging adults.

• Mechanism: Autophagy induction, mitochondrial function, polyamine synthesis
• Key Evidence: Human trials showing improved memory and cardiovascular markers
• Typical Dose: 1-6mg/day from wheat germ extract

5. Resveratrol and Pterostilbene

Evidence Rating: B+

These sirtuin activators continue to show promise, particularly when combined with NAD+ precursors. Pterostilbene offers improved bioavailability compared to resveratrol.

• Mechanism: Sirtuin activation, antioxidant effects, anti-inflammatory
• Key Evidence: Improved markers of cardiometabolic health in human trials
• Typical Dose: Resveratrol 250-500mg/day; Pterostilbene 50-150mg/day

6. Senolytics (Fisetin and Quercetin)

Evidence Rating: B

These compounds selectively eliminate senescent "zombie" cells that accumulate with age and drive inflammation and tissue dysfunction. Fisetin has emerged as particularly promising.

• Mechanism: Selective destruction of senescent cells, reduced SASP (senescence-associated secretory phenotype)
• Key Evidence: Human trials showing reduced inflammatory markers and improved physical function
• Typical Dose: Fisetin 100-500mg intermittently; Quercetin 500-1000mg

7. Alpha-Ketoglutarate (AKG)

Evidence Rating: B

This metabolic intermediate has shown impressive lifespan extension in animal models and is now being studied in humans for its effects on biological aging markers.

• Mechanism: TCA cycle support, epigenetic regulation, stem cell function
• Key Evidence: Extended healthspan in mice; human trials showing reduced biological age
• Typical Dose: 300-1000mg/day (often as calcium AKG)

8. Urolithin A

Evidence Rating: B

This postbiotic compound, derived from gut bacteria processing of pomegranate polyphenols, has shown remarkable effects on mitochondrial health through mitophagy enhancement.

• Mechanism: Mitophagy activation, mitochondrial biogenesis, muscle function
• Key Evidence: Human trials showing improved muscle endurance and mitochondrial biomarkers
• Typical Dose: 500-1000mg/day

Honorable Mentions

Several compounds narrowly missed the top 8 but show significant promise:

• Taurine: Recent 2023 Science paper showing major healthspan effects in mice
• Glycine: Supports glutathione synthesis and collagen production
• Lithium (low-dose): Epidemiological data suggests longevity effects
• CoQ10/PQQ: Mitochondrial support compounds with solid human data

Building an Evidence-Based Longevity Stack

Based on this review, here's a practical approach to anti-aging supplementation:

Foundation Stack (Strongest Evidence)

• NAD+ precursor (NMN or NR)
• Spermidine
• Resveratrol or pterostilbene

Enhanced Stack (Additional Benefits)

• Foundation stack plus:
• Periodic senolytics (fisetin + quercetin)
• Urolithin A for mitochondrial support

Prescription Consideration

• Metformin (discuss with physician)
• Low-dose rapamycin (longevity-focused physicians only)

Important Considerations

The reviewers emphasized several important points:

• Quality matters: Use products from reputable manufacturers with third-party testing
• Individual variation: Responses to supplements vary; consider biomarker tracking
• Lifestyle first: No supplement replaces exercise, sleep, nutrition, and stress management
• Evolving field: Recommendations may change as new research emerges

Conclusion

The 2024 Cell Metabolism review provides a valuable framework for evidence-based anti-aging supplementation. While no compound has been definitively proven to extend human lifespan, these 8 molecules represent our best current options for supporting healthy aging based on mechanistic understanding and available evidence.

References

[1] Lopez-Otin, C., et al. (2024). "Hallmarks of Aging: A Pharmacological Perspective." Cell Metabolism, 36(11), 2341-2367.
[2] Partridge, L., et al. (2024). "Intervening in Ageing: Translation to Humans." Nature Reviews Drug Discovery, 23, 567-589.
[3] Fontana, L., et al. (2024). "The Scientific Basis of Caloric Restriction and Pharmacological Mimetics." Science, 383(6679), 234-241.