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Longevity Pathways

mTOR, AMPK, SIRT, and autophagy.

Ranked by evidence strength across reported benefits.

Compound#1· strong

Melatonin

Pineal hormone that signals biological night — most effective for circadian-rhythm shifts.

Compound#2· strong

Coffee

Caffeine + polyphenol matrix with strong evidence for mortality and T2D reduction.

Amino Acid#3· strong

N-Acetyl Cysteine (NAC)

Glutathione precursor with mucolytic, hepatoprotective, and psychiatric uses.

Vitamin#4· strong

Vitamin B3 (Niacin)

NAD+ precursor; nicotinic acid form lowers LDL and raises HDL.

Vitamin#5· strong

Vitamin C

Water-soluble antioxidant, collagen cofactor, and immune supporter.

Herb#6· strong

Milk Thistle

Hepatoprotective herb with antioxidant and anti-fibrotic effects.

Herb#7· strong

Garlic

Culinary bulb with cardiovascular benefits primarily via allicin and aged-garlic compounds.

Amino Acid#8· strong

Glycine

Inhibitory amino acid that improves sleep quality, glycemic control, and collagen synthesis.

Compound#9· strong

Nicotinamide Riboside (NR)

NAD+ precursor with bioavailability and longevity research interest.

Compound#10· strong

NMN

NAD+ precursor similar to NR; bioavailability route debated.

Compound#11· strong

Rapamycin (Rx, reference)

mTOR inhibitor — most validated geroprotector in animal models; not a supplement.

Compound#12· strong

Metformin (Rx, reference)

Diabetes drug studied for longevity (TAME trial) via AMPK activation.

Vitamin#13· strong

Nicotinamide Riboside (NR)

NAD+ precursor that bypasses the flush — studied for cellular aging.

Compound#14· strong

Alpha-Lipoic Acid

Mitochondrial antioxidant studied for diabetic neuropathy and insulin sensitivity.

Compound#15· strong

Idebenone

Synthetic CoQ10 analog with better water solubility; used in LHON.

Mineral#16· strong

Selenium-Enriched Yeast

Yeast-bound selenomethionine — form used in major chemoprevention trials.

Compound#17· strong

ALA (R-isomer)

Natural enantiomer of α-lipoic acid with better bioavailability.

Vitamin#18· moderate

Vitamin K2 (MK-7)

Activates the proteins that direct calcium into bone — not arteries.

Compound#19· moderate

Coenzyme Q10

Mitochondrial electron carrier and lipid-soluble antioxidant.

Amino Acid#20· moderate

Glycine

Inhibitory neurotransmitter that improves sleep quality and supports collagen synthesis.

Vitamin#21· moderate

Vitamin E

Primary lipid-phase antioxidant protecting membrane PUFAs.

Herb#22· moderate

Pomegranate

Polyphenol-rich fruit converted by gut microbes to urolithin A (mitochondrial benefit).

Herb#23· moderate

Green Tea (EGCG)

Polyphenol-rich tea; EGCG modestly boosts metabolism and supports cardiovascular health.

Compound#24· moderate

DHEA

Adrenal androgen precursor declining with age; used for adrenal insufficiency and aging.

Compound#25· moderate

Astaxanthin

Algal carotenoid that is the strongest membrane antioxidant; UV and eye protection.

Compound#26· moderate

Alpha-Lipoic Acid (ALA)

Universal antioxidant that's both water and fat soluble — supports glycemic control and nerve health.

Compound#27· moderate

Ubiquinol (CoQ10)

Reduced active form of CoQ10 — preferred in adults over 40 and those with statin-induced depletion.

Vitamin#28· moderate

Vitamin K2 (MK-7)

Long-half-life K2 — directs calcium to bone and away from arteries.

Compound#29· moderate

Astaxanthin (Eye dose)

Carotenoid that crosses BBB and accumulates in ciliary body.

Amino Acid#30· moderate

Taurine

Conditionally essential amino acid involved in bile salt conjugation, osmoregulation, and cardiac function.

Compound#31· moderate

Glutathione

Master intracellular antioxidant; oral bioavailability depends on form.

Compound#32· moderate

TUDCA

Bile acid with hepatoprotective effects and ER stress reduction.

Herb#33· moderate

Ginkgo Biloba

Vasoactive herb studied for cognition in the elderly and tinnitus.

Compound#34· moderate

Shilajit

Himalayan mineral exudate rich in fulvic acid, studied for testosterone and fatigue.

Mushroom#35· moderate

Reishi

Adaptogenic mushroom used for immune balance, sleep, and stress.

Compound#36· moderate

Quercetin

Flavonoid with antihistamine and senolytic effects; pairs with bromelain or vitamin C.

Compound#37· moderate

TUDCA (Tauroursodeoxycholic Acid)

Conjugated bile acid — hepatoprotective and ER-stress-reducing.

Compound#38· moderate

Resveratrol

Polyphenol from grapes — sirtuin activator with mixed human evidence.

Amino Acid#39· moderate

Taurine

Conditionally essential amino acid with cardiovascular, metabolic, and longevity effects.

Compound#40· moderate

Fisetin

Flavonoid senolytic — clears senescent cells in animal models.

Compound#41· moderate

Sulforaphane (Broccoli Sprout)

Most potent natural Nrf2 activator — upregulates phase II detox enzymes.

Compound#42· moderate

Calcium AKG (Alpha-Ketoglutarate)

TCA-cycle intermediate — extended lifespan in C. elegans; emerging human data on biological age.

Mineral#43· moderate

Magnesium L-Threonate

Magnesium bound to L-threonic acid — the only form shown to meaningfully raise brain magnesium.

Compound#44· moderate

NMN (Nicotinamide Mononucleotide)

Direct NAD+ precursor — popular longevity supplement with growing human data.

Amino Acid#45· moderate

Taurine (High-Dose)

Conditionally essential amino acid with longevity and metabolic effects.

Mineral#46· moderate

Selenium

Trace mineral essential for glutathione peroxidase and thyroid hormone activation.

Fatty Acid#47· moderate

Krill Oil

Phospholipid-bound omega-3 with astaxanthin; better bioavailability than fish oil per gram.

Compound#48· moderate

Resveratrol

Polyphenol activating sirtuins; bioavailability and clinical effects modest.

Compound#49· moderate

Urolithin A

Gut-microbial metabolite of ellagitannins — induces mitophagy.

Amino Acid#50· moderate

L-Carnosine

Histidine dipeptide — anti-glycation and pH buffering.

Amino Acid#51· moderate

GlyNAC (Glycine + NAC)

Glycine + NAC combo — restores glutathione in older adults and improves multiple aging markers.

Herb#52· moderate

Curcumin Phytosome (Meriva)

Phosphatidylcholine-complexed curcumin — ~29× higher bioavailability than standard extract.

Mineral#53· moderate

Selenomethionine

Organic selenium form — preferred for thyroid (Hashimoto's) and antioxidant support.

Compound#54· moderate

Pterostilbene (Extra)

Methylated resveratrol analog with superior bioavailability.

Vitamin#55· moderate

Tocotrienols (Skin/Aging)

Vitamin E isoforms with 40–60× higher antioxidant power than tocopherols.

Compound#56· moderate

Trans-Resveratrol (Pure)

Purified active isomer of resveratrol.

Compound#57· moderate

Spermidine (Wheat Germ)

Polyamine that induces autophagy and may extend lifespan.

Compound#58· moderate

Urolithin A (Mitopure)

Gut-derived ellagitannin metabolite that induces mitophagy.

Vitamin#59· moderate

Mixed Tocopherols

Full-spectrum natural vitamin E avoiding α-only supplementation pitfalls.

Peptide#60· moderate

Epitalon

Tetrapeptide that activates telomerase.

Peptide#61· moderate

MOTS-c

Mitochondrial-derived peptide for metabolic regulation.

Peptide#62· moderate

SS-31 (Elamipretide)

Mitochondrial-targeted peptide for cardiolipin protection.

Compound#63· moderate

Glycine + NAC (GlyNAC)

Glutathione-boosting combination for aging.

Compound#64· moderate

Rapamycin

mTOR inhibitor studied for longevity (Rx only).

Compound#65· moderate

Metformin (Longevity Use)

Biguanide diabetes drug studied for healthspan.

Compound#66· moderate

MitoQ

Mitochondria-targeted ubiquinone (CoQ10 analog).

Compound#67· moderate

PQQ (Pyrroloquinoline Quinone)

Redox cofactor for mitochondrial biogenesis.

Compound#68· moderate

C60 in Olive Oil

Buckminsterfullerene antioxidant.

Amino Acid#69· moderate

Ergothioneine (Mushroom-Derived)

Natural ergothioneine from oyster mushrooms.

Compound#70· moderate

Hydroxytyrosol

Olive polyphenol for cardiovascular health.

Mineral#71· moderate

Selenium (Selenomethionine)

Antioxidant trace element for thyroid.

Compound#72· moderate

Trans-Resveratrol

Active form of resveratrol.

Compound#73· moderate

Micronized Resveratrol

Improved bioavailability resveratrol.

Compound#74· moderate

Punicalagin

Major pomegranate ellagitannin.

Compound#75· moderate

Ellagic Acid

Ellagitannin hydrolysis product.

Compound#76· moderate

Honokiol

Active magnolia compound.

Compound#77· moderate

Oleocanthal

EVOO ibuprofen-like compound.

Mushroom#78· limited

Lion's Mane

Edible medicinal mushroom that upregulates NGF and BDNF — studied for nerve growth and cognition.

Compound#79· limited

Fisetin

Flavonoid studied as senolytic — clearing senescent cells in animal models.

Compound#80· limited

Quercetin

Flavonoid with antihistamine, anti-viral, and senolytic activity.

Vitamin#81· limited

Tocotrienols (Vitamin E)

Unsaturated vitamin E family — superior antioxidant capacity vs alpha-tocopherol.

Mineral#82· limited

Lithium Orotate (low-dose)

Low-dose lithium salt studied for mood stability and neuroprotection.

Mushroom#83· limited

Chaga

Birch-tree mushroom rich in melanin, betulin, and antioxidants.

Compound#84· limited

PQQ

Cofactor stimulating mitochondrial biogenesis (PGC-1α).

Compound#85· limited

Pterostilbene

Bioavailable resveratrol analog with longer half-life.

Compound#86· limited

Spermidine

Polyamine inducing autophagy; epidemiologic association with longevity.

Amino Acid#87· limited

ALCAR + ALA (Mitochondrial Protection)

Mitochondrial antioxidant stack — popularized as harm-reduction adjunct for MDMA neuroprotection.

Compound#88· limited

EGCG (Green Tea Catechin)

Potent CYP/COMT-modulating antioxidant — popularized in MDMA harm-reduction stacks.

Compound#89· limited

Pterostilbene

Methylated analog of resveratrol — better bioavailability and longer half-life.

Compound#90· limited

Spermidine

Polyamine that induces autophagy — emerging longevity supplement.

Compound#91· limited

Ergothioneine

Unique antioxidant from mushrooms with its own transporter — accumulates in oxidative-stress tissues.

Compound#92· limited

Liposomal Glutathione

Phospholipid-encapsulated GSH — protects from gut breakdown for systemic delivery.

Compound#93· limited

S-Acetyl Glutathione

Acetylated GSH — stable through the gut and converted intracellularly to glutathione.

Nootropic#94· limited

9-Me-BC

β-carboline alkaloid that upregulates dopamine neurons in animal models.

Nootropic#95· limited

Centrophenoxine

Cholinergic precursor that reduces lipofuscin accumulation in neurons.

Peptide#96· limited

Thymulin (Reference)

Zinc-dependent thymic peptide that matures T-cells.

Compound#97· limited

Alpha-Ketoglutarate (AKG)

TCA-cycle intermediate studied for healthspan and frailty.

Compound#98· limited

Fisetin (Senolytic)

Polyphenol senolytic with neuroprotective and anti-inflammatory effects.

Compound#99· limited

Quercetin + Dasatinib (D+Q)

Reference senolytic combination cycled to clear senescent cells.

Amino Acid#100· limited

L-Carnosine

Dipeptide that buffers protons and reduces advanced glycation end-products.

Compound#101· limited

Ergothioneine (Extra)

Unique thiol antioxidant concentrated in mitochondria via OCTN1.