Our Science — The Hallmarks Framework Underneath the Catalog

The 60-second answer

  • Aging is a biology problem with measurable mechanisms, not a fact of life. Twelve interlocking processes — the Hallmarks of Aging framework first formalized by López-Otín, Blasco, Partridge, Serrano and Kroemer in Cell in 2013 and expanded in 2023 — describe what actually happens in cells and tissues as you age.
  • Several of those hallmarks have human trial-validated, oral interventions. NAD+ decline, sirtuin underactivity, mitochondrial dysfunction, senescent cell accumulation, autophagy decline, chronic low-grade inflammation, and methylation drift are all addressable with supplements that have peer-reviewed dose-response data in humans.
  • Our catalog mirrors the framework, hallmark by hallmark. Every product in the store sits inside one or more of the twelve hallmarks. We do not sell single-molecule cures because aging is the simultaneous decline of many maintenance systems, and a credible protocol has to address the substrate, the precursors, the activators, the cleanup machinery and the resilience layer at once.
  • What you will not find here: rapamycin, metformin, dasatinib, telomerase activators, or stem-cell mobilizers. Those belong in a clinic with bloodwork and a physician. We carry only oral, well-characterized, third-party-tested actives at trial-anchored doses.
  • Trial citations are attached. Every hallmark section below names the molecules, the doses, the delivery forms and the human studies underneath them. Read them. Bring them to your physician. Decide for yourself.

This page is the scientific spine of the catalog. If you want a fast catalog tour, read Getting Started first; if you want the protocol-by-goal view, read Protocols; if you want the per-ingredient origin file, read Ingredient Sourcing.

Why aging is now a tractable problem

For most of the twentieth century, aging was treated as a fact of life: gradual, inevitable, outside the reach of medicine. That view is no longer tenable. Over the last fifteen years, the biology of aging has resolved into a small set of measurable, druggable mechanisms. Three independent lines of evidence converged on the same picture:

The genetics line. The discovery that single-gene mutations in daf-2, age-1, and the insulin/IGF-1 pathway extended C. elegans lifespan two- to threefold (Kenyon 1993, Nature) showed that lifespan is not destiny — it is the readout of a genetically encoded program. Cynthia Kenyon's worm work, Gary Ruvkun's parallel discoveries, and Leonard Guarente's identification of sirtuins in yeast (Sir2; Kaeberlein 1999, Genes Dev) made aging a problem of cellular signaling rather than wear-and-tear.

The epigenetic line. Steve Horvath's 2013 publication of the multi-tissue methylation clock (Genome Biology) gave the field its first quantitative biomarker of biological age. The clock — and its successors GrimAge, PhenoAge, and the DunedinPACE rate-of-aging clock (Belsky 2022) — predicts all-cause mortality, cardiovascular disease, and cancer better than chronological age alone. For the first time, an intervention could be tested against a measurable readout of aging in months rather than decades.

The molecular line. The 2013 Cell paper "The Hallmarks of Aging" by López-Otín, Blasco, Partridge, Serrano and Kroemer organized the molecular biology of aging into nine hallmarks. The 2023 update (Cell, "Hallmarks of aging: An expanding universe") expanded the framework to twelve and reorganized the underlying logic into primary, antagonistic, and integrative tiers. That framework is the spine of this page and the spine of the catalog.

Acting on aging biology is no longer a fringe research program. The NIA's Interventions Testing Program (ITP) at Jackson Lab, UT Health San Antonio, and the University of Michigan has been running rigorous, double-blind, multi-site lifespan trials in mice since 2004. The TAME trial (Targeting Aging with MEtformin), led by Nir Barzilai, is the first FDA-recognized clinical trial for aging itself as an indication. Calico, Altos Labs, BioAge Labs, Loyal, Rejuvenate Bio, and a half-dozen academic Buck/Salk/Mayo-affiliated programs are running translational human work right now. The science is real. The question is what an ordinary person, with no clinical access to those programs, can put on their kitchen counter and run on themselves on a Tuesday morning. That is the question this catalog answers.

Who builds this

True Health Protocol is a small, founder-led operation run by Katy Davidovich, working with a network of formulators, contract manufacturers, and third-party testing labs. There is no PR team, no celebrity endorsement, no growth-hack marketing engine. Every product in the catalog reflects a single judgment call: does the trial bench actually support this dose, this form, this combination? If the answer is unclear, we leave the product out. If the answer is yes, we build the formula to match the trial — not the lowest bar a label-claim audit will let us get away with.

You can reach Katy directly at support@truehealthprotocol.health. Replies typically arrive within 24 hours on business days. Product feedback is read; protocol questions are answered; tough scientific questions get forwarded to people who know the answers and come back with a real reply rather than a stock template. Our manufacturing, sourcing and lab-testing standards are documented in detail at Quality and Sourcing and Ingredient Sourcing.

The Hallmarks framework — twelve mechanisms, three tiers

The 2023 update organizes the twelve hallmarks into three layers based on what they cause and what causes them:

  • Primary hallmarks (causes of damage): genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy.
  • Antagonistic hallmarks (compensatory responses gone bad): deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence.
  • Integrative hallmarks (downstream consequences): stem cell exhaustion, altered intercellular communication, chronic inflammation, dysbiosis.

The next twelve sections walk through each hallmark in order: what the mechanism is, what the trial bench supports, which catalog products map to it, and which references underwrite the doses we chose.

Hallmark 1 — Genomic instability

The mechanism. DNA accumulates damage continuously: oxidative lesions from mitochondrial ROS, double-strand breaks from replication stress, ultraviolet pyrimidine dimers, deamination, and clonal mutation. The repair machinery — base-excision repair, nucleotide-excision repair, mismatch repair, homologous recombination, non-homologous end joining — depends on poly-ADP-ribose polymerase (PARP) enzymes that consume NAD+ as a substrate. As NAD+ falls with age, PARP activity falls with it, repair fidelity slips, and somatic mutation burden rises (Massudi et al. 2012, PLOS One; Camacho-Pereira et al. 2016, Cell Metabolism).

The trial bench. Yoshino, Imai et al. 2021 (Science) showed NMN at 250 mg/day improved muscle insulin sensitivity in postmenopausal women over 10 weeks. Brakedal et al. 2022 (Cell Metabolism) — the NADPARK trial — showed NR at 1,000 mg/day raised brain NAD+ measurably in Parkinson's patients via MRS imaging. Yamaguchi et al. 2022 demonstrated 12-week NMN safety in healthy adults at 1,250 mg/day.

The catalog map. Restoring NAD+ substrate is upstream of every NAD-consuming repair enzyme: Pure NMN 500mg, NMN 1000mg Double Strength, Nicotinamide Riboside (NR) Hard Capsules, Liposomal NAD+ Ultimate 1000mg, NAD+ Daily Boost, Liquid NAD+ Drink, and NAD+ 1000mg Pure Focus Formula. See the full NAD+ Family collection for all dose tiers and delivery formats.

Hallmark 2 — Telomere attrition

The mechanism. Telomeres are the TTAGGG repeat caps that protect chromosome ends from degradation and end-to-end fusion. They shorten 50–100 base pairs per somatic cell division because DNA polymerase cannot fully replicate the lagging strand (the end-replication problem). Once a telomere drops below ~5 kb, the cell triggers replicative senescence or apoptosis. Telomere length tracks biological age and predicts cardiovascular and all-cause mortality (Cawthon et al. 2003, Lancet; Haycock et al. 2014 meta-analysis).

What the trial bench supports orally. This is one of the hallmarks where pharmacology is thin. Telomerase activators marketed as TA-65 have a single-supplier evidence base, modest signals, and we do not carry them. What does help indirectly: reducing oxidative damage to telomeric DNA. Omega-3 status, reduced inflammation, vitamin D adequacy, and folate-cycle methyl-donor sufficiency are all associated with slower telomere shortening in observational cohorts (Farzaneh-Far 2010 JAMA; Paul 2009 review).

The catalog map. Indirect support via the resilience layer: Omega-3 Fish Oil 2000mg, Vitamin D3 5000 IU + K2 MK-7, TMG 1000mg, and the antioxidant stack: Glutathione 500mg, N-Acetyl Cysteine 600mg, Astaxanthin 12mg. Browse the full Antioxidants collection and Foundational Health collection.

Hallmark 3 — Epigenetic alterations

The mechanism. The epigenome — the pattern of DNA methylation, histone modifications and chromatin architecture — drifts with age. Methyl groups added at CpG dinucleotides during embryogenesis are gradually lost, mismethylated, or relocated. The Horvath 2013 multi-tissue clock (Genome Biology) and its successors (GrimAge, PhenoAge, DunedinPACE) measure this drift and convert it to a "methylation age" that predicts mortality independent of chronological age. Sinclair's information-theory framework (Lifespan, 2019; Yang et al. 2023, Cell) treats epigenetic noise as the proximate cause of aging itself — and showed that partial reprogramming (Yamanaka factors) can reverse it in mouse retina.

The trial bench for orals. Two molecules have human methylation-clock data. Asadi Shahmirzadi et al. 2020 (Cell Metabolism) showed calcium alpha-ketoglutarate (CaAKG) extended median lifespan and compressed morbidity in mice; the TruDiagnostic 2021 prospective cohort showed an average 8-year reduction in TruAge methylation age over seven months on 1,000 mg/day. Spermidine — the polyamine produced by gut bacteria from arginine and ornithine — drives autophagy via eIF5A hypusination and EP300 inhibition; Eisenberg et al. 2016 (Nature Medicine) and the SmartAge trial established the human dose-response. Methyl-donor sufficiency (TMG, glycine, B-vitamins) supports SAM:SAH ratios that determine methyltransferase activity (Sinclair 2017 Cell; Schmeisser et al. 2013).

The catalog map. Calcium AKG 1000mg, Spermidine 10mg, TMG 1000mg, Glycine 1500mg. Pairs naturally with the NAD+ family above (sirtuins are histone deacetylases that consume NAD+ and rewrite chromatin marks).

Hallmark 4 — Loss of proteostasis

The mechanism. Cells maintain protein quality through chaperones (HSP70, HSP90), the ubiquitin-proteasome system, and autophagy. With age the chaperone network falters; misfolded proteins escape quality control and aggregate. The clinical phenotypes are familiar: amyloid-β and tau in Alzheimer's, α-synuclein in Parkinson's, transthyretin in cardiac amyloidosis. Even in non-disease aging, lipofuscin and oxidized protein adducts accumulate measurably in postmitotic tissues (Hipp et al. 2019, Cell).

The trial bench. The cleanest oral lever for proteostasis is restoring autophagic flux (covered under hallmark 5) plus reducing oxidative stress so that proteins are damaged less in the first place. Glycine and N-acetyl cysteine — the GlyNAC combination Sekhar et al. 2021 (Clinical and Translational Medicine) showed restored glutathione synthesis, reduced oxidative protein damage, and improved insulin resistance, gait speed, cognition, and inflammation markers in older adults. Curcumin clears amyloid plaque in vitro and crosses the blood-brain barrier at very modest concentrations (Shoba 1998 BioPerine bioavailability; Ringman 2012 small clinical trial in Alzheimer's).

The catalog map. N-Acetyl Cysteine 600mg + Glycine 1500mg = the GlyNAC stack at the dose tier Sekhar's lab used. Glutathione 500mg direct (enteric-coated reduced form). Curcumin 1000mg + BioPerine.

Hallmark 5 — Disabled macroautophagy

The mechanism. Autophagy is the cellular recycling system: damaged organelles, misfolded proteins, and protein aggregates are sequestered into double-membrane autophagosomes, fused with lysosomes, and degraded. Mitophagy is the mitochondria-specific subroutine. Both decline with age (Hansen 2018, Nat Rev Mol Cell Biol). Caloric restriction extends lifespan in every model organism tested, and autophagy induction is the proximate mechanism (Madeo, Zimmermann et al. 2015 Cell).

The trial bench. Three orals have credible human autophagy-induction data. Spermidine (Eisenberg 2016 Nature Medicine) — directly induces autophagy via eIF5A hypusination; the SmartAge trial in older adults showed memory improvement at 1.2 mg/day from wheat germ extract. Urolithin A (Andreux 2019 Nature Metabolism; the MITOPURE trials) — drives mitophagy specifically through PINK1/Parkin signaling; the postbiotic form is more reliable than ellagic-acid precursors because only ~40% of adults harbor the gut microbes that convert ellagitannins to urolithin A. Resveratrol and pterostilbene drive AMPK-mTOR-autophagy axis activation (Park et al. 2012 Cell).

The catalog map. Spermidine 10mg, Urolithin A 500mg, Resveratrol 600mg, Pterostilbene 100mg.

Hallmark 6 — Deregulated nutrient sensing

The mechanism. Four conserved pathways sense nutrients and route signals toward growth (when fed) or maintenance (when fasted): the insulin/IGF-1 axis, mTOR (mechanistic target of rapamycin), AMPK (AMP-activated protein kinase), and sirtuins. With age the dial gets stuck in growth mode — chronically high insulin, IGF-1, and mTOR signaling, with falling AMPK and sirtuin activity. Genetic suppression of insulin/IGF-1 signaling extends lifespan in worms, flies, and mice (Kenyon 1993; Holzenberger 2003 Nature).

The trial bench. AMPK activation is the most accessible oral lever. Berberine — Lan et al. 2015 meta-analysis (J Ethnopharmacol) of 27 RCTs, 2,569 patients — demonstrated berberine HCl at 1,500 mg/day produces glucose-lowering and lipid effects comparable to metformin in type 2 diabetes and metabolic syndrome. The mechanism is direct AMPK activation via inhibition of mitochondrial complex I. Alpha-lipoic acid — racemic ALA — has Ziegler 2011 NATHAN1 trial data for diabetic neuropathy at 600 mg/day and is a redox-active mitochondrial cofactor. Sirtuin support (covered above) and NAD+ substrate (covered under hallmark 1) feed the same nutrient-sensing network.

The catalog map. Berberine HCL 500mg, Alpha-Lipoic Acid 600mg. Pairs naturally with the NAD+ Family and sirtuin activators. Browse the Metabolic collection for the full dial.

Hallmark 7 — Mitochondrial dysfunction

The mechanism. Mitochondria are the cell's energy organelles. With age they accumulate mtDNA mutations (more vulnerable than nuclear DNA because they sit next to the electron transport chain and the ROS it generates), lose membrane potential, fragment, and fail to clear themselves through mitophagy. The result: less ATP, more ROS leak, more nuclear DNA damage from spillover oxidants, and downstream activation of senescence and inflammation programs. Mitochondrial decline is the proximate driver of sarcopenia, exercise intolerance, and many neurodegenerative phenotypes (Sun et al. 2016, Mol Cell).

The trial bench. Coenzyme Q10 — Mortensen et al. 2014 Q-SYMBIO trial (JACC: Heart Failure) — 100 mg three times daily reduced major adverse cardiovascular events 43% over two years in symptomatic heart failure patients vs placebo, with a parallel reduction in all-cause mortality. PQQ (pyrroloquinoline quinone) drives mitochondrial biogenesis through PGC-1α (Chowanadisai 2010 J Biol Chem; Harris 2013 small clinical trial). Urolithin A drives mitophagy through PINK1/Parkin (Andreux 2019). NAD+ supplies the substrate the electron transport chain runs on.

The catalog map. CoQ10 400mg, PQQ 20mg, Urolithin A 500mg, Alpha-Lipoic Acid 600mg. Browse the full Mitochondrial Renewal collection.

Hallmark 8 — Cellular senescence

The mechanism. When a cell takes too much DNA damage, runs out of telomere, or sits under chronic stress, it withdraws from the cell cycle but does not die. These senescent cells secrete a cocktail of inflammatory cytokines, matrix metalloproteinases, and growth factors — the senescence-associated secretory phenotype (SASP) — that locally remodels tissue and propagates senescence to neighbors. Even at low single-digit percentages of total cells, senescent cells drive disproportionate dysfunction (van Deursen 2014 Nature; Baker 2016 Nature — selective genetic ablation of p16-positive cells extended median mouse lifespan 25%).

The trial bench. Two flavonoid orals have senolytic data in humans. Fisetin — Yousefzadeh et al. 2018 (EBioMedicine) demonstrated senolytic activity in vitro and in mice; the Mayo Clinic AFFIRM trials (NCT03675724, NCT04210986) used 20 mg/kg/day pulse dosing in older adults with osteoarthritis and frailty. Quercetin combined with dasatinib (D+Q) is the most-cited senolytic regimen; oral quercetin alone has dose-response data and pairs naturally with fisetin. Apigenin inhibits CD38 — the principal NAD+-consuming hydrolase that drives age-related NAD+ decline (Camacho-Pereira 2016 Cell Metab; Escande 2013) — making it a senolytic-adjacent intervention that also raises NAD+ availability.

The catalog map. Fisetin 500mg, Quercetin 500mg, Apigenin 50mg + BioPerine. Browse the full Senolytics collection. The standard usage pattern is pulse dosing (2 days/month) rather than daily.

Hallmark 9 — Stem cell exhaustion

The mechanism. Tissue-resident stem cells (hematopoietic, intestinal, satellite-muscle, neural) lose self-renewal capacity with age. Hematopoietic stem cell pools become biased toward myeloid output and lose lymphoid potential — the immunological substrate of immunosenescence. Muscle satellite cells lose Notch signaling and replicative capacity, contributing to sarcopenia. Neural stem cells in the dentate gyrus and subventricular zone shrink (de Haan and Lazare 2018 Blood).

What the trial bench supports orally. No oral supplement reverses stem-cell exhaustion directly; that is exosome and pharmacological territory. What helps indirectly: reducing the inflammatory and oxidative burden on the stem cell niche (anti-inflammatories, antioxidants), supporting the methyl-donor pool that stem cells depend on for self-renewal (TMG, glycine, B-vitamins), and maintaining the nutrient-sensing balance that keeps stem cells in maintenance rather than premature differentiation (AMPK activators, sirtuin support).

The catalog map. Indirect support: the Foundational Health, Antioxidants, and Metabolic collections cover the upstream resilience factors. Creatine Monohydrate has the strongest oral evidence base for muscle-satellite-cell preservation and sarcopenia prevention in adults over 50 (Devries and Phillips 2014 meta-analysis, Med Sci Sports Exerc).

Hallmark 10 — Altered intercellular communication

The mechanism. With age, the signaling environment between cells degrades: hormone secretion patterns shift (insulin resistance, growth-hormone decline, sex-hormone drop), the inflammatory tone rises (covered separately as hallmark 11), neuromuscular junctions atrophy, and tissue crosstalk becomes noisy. Acetylcholine, dopamine, serotonin and stress-axis signaling all show measurable age-related drift.

The trial bench. The HPA-axis-resilience and stress-signaling lever has the cleanest oral evidence. KSM-66 ashwagandha (Chandrasekhar 2012 Indian J Psychol Med; Salve 2019 Cureus) reduces serum cortisol 27.9% over 60 days and improves sleep onset latency, perceived stress, and DHEA-S. The Sekhar 2021 GlyNAC trial showed restored glutathione synthesis improves multiple integrative endpoints — gait speed, cognition, inflammation — in older adults, suggesting the redox milieu mediates much of the cell-cell communication signal. Magnesium glycinate supplies the cofactor for over 300 enzymatic reactions including NMDA-receptor modulation and HPA-axis attenuation.

The catalog map. Ashwagandha KSM-66 600mg, Magnesium Glycinate 400mg, the GlyNAC pair (NAC + Glycine, above). Browse Foundational Health for the full resilience layer.

Hallmark 11 — Chronic inflammation ("inflammaging")

The mechanism. The 2023 update elevated chronic low-grade sterile inflammation to a stand-alone hallmark, separate from infection-driven acute inflammation. With age, baseline IL-6, TNF-α, CRP, and NLRP3-inflammasome activity all rise. The drivers are multifactorial: SASP secretions from senescent cells (hallmark 8), gut barrier dysfunction (hallmark 12), mitochondrial DAMPs released from damaged organelles (hallmark 7), and glycation end-products from chronic hyperglycemia. Inflammaging is the integrative output of multiple primary hallmarks and the proximate driver of cardiovascular, neurodegenerative, sarcopenic, and autoimmune phenotypes (Franceschi 2018 Nat Rev Endocrinol).

The trial bench. Curcumin at 1,000 mg/day with piperine has reduced CRP, IL-6 and TNF-α across multiple meta-analyses (Derosa 2016; Sahebkar 2014). Omega-3 EPA/DHA at 2,000 mg/day reduces inflammatory cytokines (Calder 2017 Biochem Soc Trans); the VITAL trial (Manson 2019 NEJM) and REDUCE-IT (Bhatt 2019 NEJM) provide cardiovascular endpoint data at clinical doses. Vitamin D adequacy reduces inflammatory markers across multiple cohorts; the VITAL trial again provides the cleanest US trial data at 2,000 IU/day.

The catalog map. Curcumin 1000mg + BioPerine, Omega-3 Fish Oil 2000mg, Vitamin D3 5000 IU + K2 MK-7, Quercetin 500mg (also a mast-cell stabilizer and anti-inflammatory). Browse Cardiovascular Longevity for the full anti-inflammaging stack.

Hallmark 12 — Dysbiosis

The mechanism. The gut microbiome is the largest endocrine, metabolic and immunological organ in the body — 100 trillion microbes producing short-chain fatty acids, secondary bile acids, vitamin K2, urolithins, equol, neuroactive metabolites, and trimethylamine. With age the microbiome loses diversity, gains pathobiont overgrowth (Enterobacteriaceae), and the intestinal barrier loosens — driving systemic LPS endotoxemia and feeding back into hallmark 11. The 2023 update added dysbiosis as a stand-alone hallmark on the strength of the centenarian-microbiome literature (Bian 2017; Biagi 2016 Curr Biol).

The trial bench for orals (limited but real). Polyphenols — resveratrol, curcumin, quercetin, fisetin, the entire flavonoid catalog — are converted by gut bacteria into bioactive metabolites and modulate the gut barrier (Tuohy 2012; Cardona 2013). Urolithin A is itself a bacterial metabolite. Glycine and TMG support the methyl-donor and sulfur-amino-acid pools that gut epithelium turns over rapidly.

The catalog map. Indirect support through the polyphenol / antioxidant stacks already named: Resveratrol, Curcumin, Quercetin, Urolithin A, plus methyl-donor and substrate support (TMG, Glycine).

The foundational substrate — what underpins everything above

Before any longevity-active does its job, baseline biology has to be intact. Five nutrients in particular are quietly rate-limiting for nearly everything else in the protocol:

  • Magnesium. A required cofactor for over 300 enzymatic reactions including the NAMPT step in NAD+ salvage, every ATP-binding step, and DNA polymerases. The TRAACS bisglycinate chelate form (Magnesium Glycinate 400mg) avoids the GI tolerability issues of magnesium oxide and citrate and crosses into tissue more reliably.
  • Vitamin D + K2. The CYP27B1-activated calcitriol pathway plus K2-MK7's role in routing calcium away from soft tissue and into bone. The Knapen 2015 trial (Thrombosis Haemostasis) is the cleanest carboxylation trial for the dose we use — 5,000 IU D3 + 100 mcg MK-7. Vitamin D3 5000 IU + K2 MK-7.
  • Omega-3 EPA/DHA. Membrane phospholipid composition, resolution of inflammation, cardiovascular endpoints across the VITAL and REDUCE-IT trials. We use re-esterified triglyceride form (TG, not ethyl ester) per Dyerberg 2010 (PLEFA) bioavailability data. Omega-3 Fish Oil 2000mg.
  • Taurine. The conditionally essential sulfur amino acid Singh, Bhasin et al. 2023 (Science) showed extended median lifespan in mice and worm models, with falling serum levels closely tracking biological age in human cohorts. Taurine 1000mg.
  • Creatine monohydrate. The most-replicated supplement in the literature for lean-mass preservation in adults over 50 (Devries and Phillips 2014 meta-analysis). Creatine also acts as a brain-energy buffer and crosses the blood-brain barrier at modest concentrations. Creatine Monohydrate 1000mg.

You will see these five repeatedly framed as "foundational." They are not the headline acts. They are the floor everything else stands on. Browse the full Foundational Health collection.

Beauty, skin and connective tissue — extending the framework

Skin and connective tissue have their own subset of hallmark mechanisms: collagen and elastin crosslinking by glycation end-products, hyaluronic acid depletion in the dermal matrix, melanocyte dysregulation, and barrier-lipid loss. Three orals have meaningful trial data here. Marine collagen peptides at 2.5–10 g/day (Proksch 2014 Skin Pharmacol Physiol; Choi 2014; Asserin 2015) show measurable improvement in skin elasticity and dermal density at 8–12 weeks. Multi-collagen blends supply the Type I/III/V/X distribution of native dermal matrix plus chicken-sternum Type II for joint cartilage (UC-II spec). Hyaluronic acid orals at 120–200 mg/day (Oe 2017 Clin Cosmet Investig Dermatol) show skin moisture and elasticity endpoints.

The catalog map. Marine Collagen Peptides 5000mg, Multi Collagen Complex (5 Types, capsules), Multi Collagen Peptides Powder 1lb, Hyaluronic Acid 200mg + Vitamin C, Biotin 10,000mcg, Liposomal Vitamin C 1000mg, Astaxanthin 12mg, Beauty and Longevity Stack. Browse the full Collagen collection, Beauty and Anti-Aging, and Skin Protocol.

The biomarker layer — what to actually measure

If you are running a longevity protocol on yourself, the question that matters most is whether it is working. Three categories of biomarkers have clinical utility today:

Conventional bloodwork (annually, or quarterly if you are optimizing). CBC, comprehensive metabolic panel, lipid panel including ApoB, LDL particle number, Lp(a), HbA1c, fasting glucose and insulin (with HOMA-IR), high-sensitivity CRP, fasting homocysteine, ferritin, TSH and free T4, vitamin D 25-OH, B12, folate, magnesium RBC, omega-3 index. This panel is widely available through Labcorp, Quest, Ulta Lab Tests, Marek Health, Function Health and InsideTracker. It is the bedrock — almost every supplement decision should be readable against it.

Methylation age clocks (annually, every 6 months if optimizing aggressively). TruDiagnostic TruAge, Elysium Index, GrimAge research access through Yale-affiliated labs, MyDNAge. Horvath, GrimAge, PhenoAge and DunedinPACE all have published longitudinal validation. These are the closest thing the field has to a quantitative readout of "is this protocol slowing biological aging" on a months-to-years timescale rather than decades.

Functional and body-composition (continuous). Grip strength (Jamar dynamometer, $50 home unit), VO2 max (gym treadmill or Garmin/Apple Watch estimate, fitness-watch-grade is acceptable), DEXA body composition (annual, $50–150), resting heart rate and HRV (continuous from any wearable), sleep architecture (continuous from Oura, Whoop, or any clinical-grade tracker), and gait speed (six-meter walk test, smartphone). Two of these — VO2 max and grip strength — predict all-cause mortality independent of every other risk factor (Studenski 2011; Leong 2015).

We do not sell or affiliate with any of these. We name them so you can run your own measurement loop on whatever supplements you choose to take, ours or otherwise. If a supplement isn't moving any of your biomarkers in three to six months, that is the answer.

Quality, sourcing and manufacturing — what the catalog does about it

The science above is only as useful as the actual molecule that arrives in the bottle. Three failure modes are common in the supplement industry:

Wrong isomer. NMN sold without isomer disclosure is frequently the inactive α-NMN; we specify ≥99% β-NMN. Resveratrol sold as "resveratrol" without the trans- prefix is frequently a cis/trans mix; we specify ≥98% trans-resveratrol. Pterostilbene and astaxanthin have similar isomer-disclosure traps.

Wrong form. Magnesium oxide is poorly absorbed and laxative; magnesium bisglycinate (the TRAACS chelate form, FT-IR-verified) is reliably absorbed without the GI consequence. Vitamin K2 as MK-4 has a half-life of hours; MK-7 has a half-life of days and is the form Knapen used in trial. Curcumin without piperine has bioavailability under 1%; curcumin with BioPerine has 20× the bioavailability per Shoba 1998.

Wrong testing. Most supplements are not tested for heavy metals, pesticides, residual solvents or microbial contamination at all. We require a three-tier testing protocol — HPLC identity and ≥90% potency, ICP-MS heavy metals against California Proposition 65 daily limits (Pb ≤0.5µg, Hg ≤0.3µg inorganic / 0.7µg methyl, Cd ≤4.1µg, inorganic As ≤10µg), USP <2021>/<2022> microbial, EU MRL pesticide screening, USP <467> residual solvents, USP <701> disintegration. Per-batch Certificate of Analysis is available on request through support@truehealthprotocol.health.

The full sourcing and testing standard, including per-ingredient origin and supplier traceability, is documented at Quality and Sourcing and Ingredient Sourcing.

How to actually use this catalog — three reading paths

Path 1: I'm new to longevity supplements. Start with Getting Started. It walks you through a foundational 4-week build (Magnesium Glycinate, D3+K2, Omega-3, NMN or NR, Resveratrol, Multi Collagen) before adding senolytics or metabolic actives. The Starter Bundles collection assembles these into single-SKU starter kits. The Longevity Essentials collection is the next-tier expansion.

Path 2: I want a stack for a specific goal. Read Protocols. It covers the Sinclair Stack, Senolytic Burst, GlyNAC Master Antioxidant, Mitochondrial Renewal, Skin and Beauty, Cardiovascular Longevity, Brain and Cognitive, and Foundational Health stacks — each with the trial-anchored dosing, timing windows, drug-interaction notes, and per-product cross-links. Goal-specific collections include Metabolic, Mitochondrial Renewal, Senolytics, Brain and Cognitive, Cardiovascular, Fertility, and Skin Protocol.

Path 3: I want to understand a specific molecule before I buy it. Each product page has the trial citations, the dose rationale, the form and isomer specification, the country of origin, and the standard usage timing. The most-detailed reference pages are Ingredient Sourcing (origin and supplier per ingredient) and FAQ (drug interactions, pregnancy, vegan status, third-party testing, US shipping and 30-day returns).

What this site will say — and what it won't

We will not tell you that a supplement cures, treats or prevents disease. The FDA does not allow that claim and, more importantly, no supplement does. What supplements can do — and what the trial bench actually supports — is shift biological readouts: NAD+ levels rise, methylation age slows, cortisol falls, inflammatory cytokines drop, mitochondrial function improves, lean mass holds. Those are the claims we make, and they are the claims you can verify against your own bloodwork and biomarker panel.

We will not tell you a single product is a "longevity miracle." Aging is twelve interlocking mechanisms, and any product addressing one of them will look modest in isolation. The trial-bench rationale for our catalog is layered: foundational substrate first, then NAD+ family, then sirtuin activators, then mitochondrial support, then senolytics on a pulse schedule, then methylation and resilience cofactors. The protocol is the product. Read the Protocols page for the assembly logic.

We will not silently substitute cheaper forms or sources to protect margin. If a product specs ≥99% β-NMN and the supplier batch comes back at 96%, we hold the batch and re-source — we do not relabel. If a Certificate of Analysis fails any of the seven testing tiers, the batch does not ship. The cost of holding inventory is real; the cost of shipping a substandard batch is worse.

We will not sell prescription pharmacology — rapamycin, metformin, dasatinib, low-dose lithium, GHK-Cu peptides, BPC-157 — under any framing. Those belong in a clinic with bloodwork and a physician. Several of them have superb longevity rationale; none of them belong in a consumer supplement catalog. We carry only oral, well-characterized, third-party-tested actives at trial-anchored doses.

The catalog at a glance

The store carries 40 active SKUs organized into the following collections. Each link goes to the live collection page with current pricing, stock status, and per-product trial citations.

Selected primary references

The following are the trials and review papers most directly underwriting the catalog's dose, form, and protocol logic. Dates are publication years; all are peer-reviewed.

  1. López-Otín, Blasco, Partridge, Serrano, Kroemer. The Hallmarks of Aging. Cell 153 (2013); Hallmarks of aging: An expanding universe. Cell 186 (2023).
  2. Horvath. DNA methylation age of human tissues and cell types. Genome Biology 14 (2013).
  3. Belsky et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife 11 (2022).
  4. Yoshino, Imai et al. Long-term administration of nicotinamide mononucleotide improves muscle insulin sensitivity in postmenopausal women. Science 372 (2021).
  5. Brakedal et al. The NADPARK study: a randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metabolism 34 (2022).
  6. Trammell et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature Communications 7 (2016).
  7. Howitz, Sinclair et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425 (2003).
  8. Hubbard et al. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 339 (2013).
  9. Asadi Shahmirzadi et al. Alpha-Ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice. Cell Metabolism 32 (2020).
  10. Eisenberg et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nature Medicine 22 (2016).
  11. Andreux et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism 1 (2019).
  12. Yousefzadeh et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine 36 (2018).
  13. Sekhar et al. GlyNAC supplementation in older humans improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation and insulin resistance. Clinical and Translational Medicine 11 (2021).
  14. Mortensen et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO. JACC: Heart Failure 2 (2014).
  15. Ziegler et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care 34 (2011).
  16. Lan et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipidemia and hypertension. J Ethnopharmacol 161 (2015).
  17. Knapen et al. Vitamin K2 supplementation improves arterial stiffness in healthy postmenopausal women. Thrombosis and Haemostasis 113 (2015).
  18. Chandrasekhar et al. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root. Indian J Psychol Med 34 (2012).
  19. Shoba et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Medica 64 (1998).
  20. Singh, Bhasin et al. Taurine deficiency as a driver of aging. Science 380 (2023).
  21. Manson et al. Vitamin D supplements and prevention of cancer and cardiovascular disease (VITAL). NEJM 380 (2019).
  22. Bhatt et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia (REDUCE-IT). NEJM 380 (2019).
  23. Forbes et al. Effects of creatine supplementation on properties of muscle, bone, and brain function in older adults: a narrative review. J Diet Suppl 19 (2022).
  24. Camacho-Pereira et al. CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metabolism 23 (2016).
  25. Studenski et al. Gait speed and survival in older adults. JAMA 305 (2011).
  26. Leong et al. Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study. Lancet 386 (2015).
  27. Proksch et al. Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology. Skin Pharmacol Physiol 27 (2014).
  28. Yamaguchi et al. Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men. Endocrine Journal 69 (2022).

How we revise this page

The science of aging is one of the fastest-moving areas in biomedicine. Trials publish weekly. Meta-analyses replace single trials. New molecules graduate from cell-culture to mouse to human. We update this page when a meaningful new trial lands — recent updates include the addition of dysbiosis as a stand-alone hallmark following the 2023 framework expansion, the integration of the DunedinPACE clock alongside Horvath/GrimAge/PhenoAge, the NADPARK 2022 brain-NAD+ MRS data for NR, and the Singh/Bhasin 2023 Science paper repositioning taurine as a core foundational substrate.

If you find a citation that should be here and isn't, or a claim that no longer reflects the current literature, write to support@truehealthprotocol.health. We read every email, and corrections to this page get priority.

Honest closing

Nothing on this page is a promise of longer life. The evidence above is suggestive, mechanism-grounded, and built from the cleanest human trials available — but human longevity trials run on the timescale of human lives, and the field is younger than most of the people working in it. What we can say with confidence is that the molecules we sell, at the doses we sell them at, in the forms we sell them in, have peer-reviewed human data showing measurable shifts in biological aging readouts. Whether those readouts translate into more healthy years is the bet you are making by taking them, and the same bet we are making by building this catalog.

Read carefully. Test conservatively. Bring your bloodwork to your physician. Decide for yourself.

These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease. The information on this page is educational and reflects published peer-reviewed literature; it is not medical advice and is not a substitute for the judgment of your physician. Pregnant or nursing women, individuals with chronic conditions, and individuals taking prescription medications — particularly anticoagulants, statins, antihyperglycemics, immunosuppressants, or chemotherapy — should consult a qualified healthcare provider before beginning any supplementation. See the FAQ for our drug-interaction summary and the Refund Policy and Shipping Policy for fulfillment details. Catalog browse: All Products.