Longevity & Anti-aging

The Body's Own Repair Signal — And the Evidence Gap Between What It Does and How People Use It

The ITP Mouse Data: Lifespan Extended at Multiple Labs, Doses, and Start Ages. The PEARL Trial (April 2025): First 48-Week Placebo-Controlled Human Longevity Trial Published. The Bioavailability Finding That Changes Everything: Compounded Rapamycin Is ~3x Less Bioavailable Than Commercial. Intermittent vs Continuous Dosing: The Pharmacological Divide Between Transplant Medicine and Longevity Use. The Immunosuppression Risk That Needs Honest Framing. The Drug Interaction Profile That Makes This one of the highest-interaction-risk compounds in this reference set to Stack. Why the Community Uses ~6 mg Weekly. What Happens When You Stop.

A core longevity target with a heavily commercialized supplement ecosystem. The Most Commercially Weaponized. The Man Promoting NMN Has Financial Ties to NMN. The Man Criticizing Him Has Financial Ties to NR. The Clinical Evidence Is Real and More Modest Than Either Side Tells You.

The Only Senolytic With Real Human Trial Data. Tested at the Mayo Clinic. Proven to Clear Senescent Cells in Humans. Dasatinib Is a Chemotherapy Drug. The Community Is Using It Without Prescriptions, ECGs, or Drug Interaction Screens.

Reported to Be 10 Million Times More Potent Than BDNF. The Foundational Mechanistic Data Is Under a Research Integrity Cloud. The Clinical Prodrug Failed Phase 2/3. The Community Uses It Anyway.

40 Years of Research From One Lab. The Most Cited Telomere Peptide in the Longevity Space. The First Independent Replication Was Published in 2025.

The World's Best-Selling Senolytic Supplement. One Landmark Mouse Study. One ITP Failure. Multiple Human Trials Running for Years With No Published Senolytic Endpoint Data. The Bioavailability Problem Nobody in the Marketing Ecosystem Discusses.

A 2017 Paper Showed It Extended Mouse Lifespan by 24.8%. The Community Is Already Injecting It. There Has Never Been a Human Safety Trial. And It Works by Interfering With p53.

NOTE: This chapter covers GHK as a free tripeptide — its endogenous biology, copper-carrier function, and primary topical cosmetic applications. The systemic, injectable, and regenerative applications of the copper-chelated complex are covered in the GHK-Cu chapter, which should be read alongside or before this chapter. Plasma Levels: 200 ng/mL at Age 20, Declining to 80 ng/mL by Age 60. The Connectivity Map and 4,000 Genes. Loren Pickart (1938–2023). The Copper Switch.

Found in Surviving Brain Cells of an Alzheimer's Patient. Encoded in Mitochondrial DNA. Higher in Centenarians' Children. Inversely Correlated With IGF-1. The GH Axis the Community Raises for Anti-Aging Suppresses It.

The Drug That Reversed Brain Aging in Mice. Discovered by Phenotypic Screen. Target Unknown for 7 Years. ATP Synthase: The Unexpected Bridge Between Alzheimer's and Aging. BDNF Induction. AMPK/mTOR via a Completely Novel Entry Point. Phase 1 Human Safety Trial Completed (NCT03838185). The Compound That Is Structurally Related to Curcumin But Pharmacologically Nothing Like It.

Four Organ-Specific Bioregulators from the Russian Khavinson Research Tradition. The Theory That Short Peptides Regulate Gene Expression in a Tissue-Specific Way. Cortexin: A Russian-Approved Neuroprotective Extract with Multi-Receptor Activity. CardioCytogen (Ala-Glu-Asp-Arg): The Cardiac Fibroblast Modulator. Crystagen: Connective Tissue and Cartilage Bioregulator. Bronchogen: Pulmonary Bioregulator Tetrapeptide. The Shared Evidence Architecture That Applies to All Four.

40+ Years of Russian Research. 500+ Publications. One Institution. The Most Concentrated Single-Lab Provenance of Any Compound Class in this reference. Vladimir Khavinson (1946-2024) and the St. Petersburg Institute of Bioregulation and Gerontology. The Epigenetic Chromatin Mechanism. The Cytomax vs Cytogen Distinction. The 6-to-8-Year Mortality Study. The 2025 Independent Replication That Changed the Evidence Conversation. 14 Organ-Specific Bioregulators — Their Sequences, Targets, Evidence, and Protocols.

Every Cell Makes It. Every Major Disease Depletes It. Oral Supplementation Below 1% Bioavailability in Standard Form. IV Delivery With Documented Fatalities. A Billion-Dollar Skin Whitening Industry Built on Mixed Evidence. The Precursor Strategy That Outperforms the Molecule Itself.

The TAME Trial: The First FDA-Recognized Study to Use 'Aging' as a Drug Indication. The Bannister Study: Diabetics on Metformin Outlive Non-Diabetics. The 2024 Cell Primate Paper: 6.1-Year Brain Aging Regression. The Exercise Controversy: Metformin Blunts the Mitochondrial Benefits of Training. B12 Depletion: The Most Important Long-Term Safety Issue. Metformin vs Rapamycin: The Same mTOR Pathway, Different Entry Points. Who Benefits Most. Who Shouldn't Use It.

Mitochondrial-derived peptide studied for AMPK signaling, metabolic stress resilience, and exercise-mimetic pathways.

First Signaling Peptides Derived from the Mitochondrial Genome

Short Khavinson tripeptide positioned for brain and pineal-gland bioregulation. The appeal is cognitive aging, neuroprotection, and circadian support; the limitation is that the evidence is mostly single-institution preclinical work, not human clinical validation.

The Drug That Extended Rat Lifespan in 1988 and Still Fascinates the Longevity Community. Irreversible MAO-B Inhibitor. Dopamine Preservation. BDNF Upregulation. The DATATOP Trial: Symptomatic Effect, Not Neuroprotection — The Distinction That Matters. The Amphetamine Metabolites: L-Enantiomers Only — What That Means Clinically. Low-Dose Community Protocols (1-5 mg Every Few Days). Why High-Dose Loses MAO-B Selectivity and What Happens Then. Selegiline vs Rasagiline. The Cheese Reaction: When It Applies and When It Doesn't.

The Metabolically Active Member of a Six-Peptide Family From the Same Mitochondrial Gene as Humanin. A Receptor Has Been Found. An Obesity Protection Mechanism Has Been Identified. Lower Levels Are Associated With Prostate Cancer Risk. No Human Trial Has Been Run.

Every Other MDP in this reference Keeps Cells Alive. SHLP6 Tells Them to Die. This May Be Exactly the Point — and the Most Underappreciated Mechanism in the Entire Mitochondrial Peptide Family.

SS-31's Sister Compound. Targets the Same Mitochondrial Membrane. Cannot Scavenge Free Radicals. Works Anyway. Which Proves Something Important About How SS-31 Actually Works.

The Only FDA-Approved Mitochondrial Therapeutic. Most Clinical Trials Failed. The Basic Science Is Compelling. All Three of These Things Are True Simultaneously.

Approved in 37+ Countries. The Most Extensively Studied Thymic Peptide in Clinical Medicine. 30+ RCTs. 11,000+ Subjects. HBeAg Seroconversion RR 2.31. A Positive Sepsis Trial in 2013 Followed by a Definitive Negative Phase 3 in 2025. The US Regulatory Rollercoaster: Category 2 (2023) → Nomination Withdrawn (2024) → Pending PCAC Review (2026). Immunomodulator, Not Immunostimulant — A Critical Distinction.

The Only Thymic Hormone That Requires a Metal Cofactor. Biologically Inactive Without Zinc. The Most Important Clinical Point: Zinc Deficiency Causes Functional Thymulin Deficiency — And Zinc Supplementation Restores It. One Human Interventional Study from 1982. Extensive Animal Evidence. The Chapter That Is Also a Zinc Education.