Geroprotect Science
A deeper look at
the evidence.
Primary sources, evidence boundaries, safety context and the biology behind the Geroprotect research programme.
How to read this section
Evidence is
not one thing.
Human trials, observational studies, animal models and cell experiments answer different questions. A mechanism can justify research; it cannot establish that a finished supplement improves health or lifespan.
Separate the model
We state whether evidence comes from people, animals, cells or a mechanistic hypothesis.
Keep nulls visible
Negative, mixed and primary-endpoint results belong beside positive findings.
Follow the source
Primary papers and authoritative registries are linked where available.
Disclose interests
Geroprotect sells these formulas. Relevant commercial funding is part of the record.
26-actives research map
Composition,
amount and study type.
These categories describe selected ingredient-level literature. They do not show that either complete formula—or the two-formula combination—has been clinically tested.
- Human RCT
- Random allocation in people; supports only the population, dose, duration and endpoint actually tested.
- Human clinical
- Human dosing, pharmacokinetic or safety work that may not test efficacy or a clinical outcome.
- Human observational
- Associations in people; useful for hypotheses, but unable by itself to establish cause and effect.
- Animal
- Whole-organism preclinical evidence; informative for biology, not proof of a human benefit.
- In-vitro
- Cell-free or cell experiments; mechanistic evidence at exposures that may not translate to oral use.
Source coverage: linked ingredient names open a reviewed, source-rich Blog note. Unlinked rows are high-level study-type summaries pending a dedicated source review; they should not be cited as standalone proof.
| Active | Formula | Amount | Study types represented |
|---|---|---|---|
| Ca-AKG | Essentials I | 450 mg | Human RCTHuman clinicalHuman observationalAnimalIn-vitro |
| NMN | Essentials I | 450 mg | Human RCTHuman clinicalAnimalIn-vitro |
| Quercetin | Essentials I | 300 mg | Human RCTHuman clinicalHuman observationalAnimalIn-vitro |
| Fisetin | Essentials I | 300 mg | Human RCTHuman clinicalAnimalIn-vitro |
| Pterostilbene | Essentials I | 100 mg | Human RCTAnimalIn-vitro |
| Curcumin | Essentials I | 150 mg | Human RCTHuman clinicalAnimalIn-vitro |
| Berberine | Essentials I | 315 mg | Human RCTHuman clinicalAnimalIn-vitro |
| Urolithin A | Essentials I | 200 mg | Human RCTAnimalIn-vitro |
| Coenzyme Q10 | Essentials I | 150 mg | Human RCTHuman clinicalHuman observationalAnimalIn-vitro |
| Apigenin | Essentials I | 150 mg | Human clinicalHuman observationalAnimalIn-vitro |
| PQQ | Essentials I | 40 mg | Human RCTHuman clinicalAnimalIn-vitro |
| 5-Aminolevulinic Acid (5-ALA) | Essentials I | 30 mg | Human RCTHuman clinicalAnimalIn-vitro |
| Spermidine | Essentials I | 3 mg | Human RCTHuman observationalAnimalIn-vitro |
| Nicotinamide Riboside (NR) | Essentials II | 480 mg | Human RCTHuman clinicalAnimalIn-vitro |
| Resveratrol | Essentials II | 360 mg | Human RCTHuman clinicalHuman observationalAnimalIn-vitro |
| EGCG (Epigallocatechin Gallate) | Essentials II | 240 mg | Human RCTHuman clinicalAnimalIn-vitro |
| Luteolin | Essentials II | 240 mg | Human clinicalHuman observationalAnimalIn-vitro |
| Baicalein | Essentials II | 360 mg | Human RCTHuman clinicalAnimalIn-vitro |
| Fucoidan | Essentials II | 360 mg | Human RCTHuman clinicalAnimalIn-vitro |
| Ginsenosides (80% purity) | Essentials II | 360 mg | Identity profile pending |
| Withaferin A | Essentials II | 18 mg | Human clinicalAnimalIn-vitro |
| Genistein | Essentials II | 60 mg | Human RCTHuman clinicalHuman observationalAnimalIn-vitro |
| L-Ergothioneine | Essentials II | 24 mg | Human RCTHuman observationalAnimalIn-vitro |
| Pentadecanoic Acid (C15:0) | Essentials II | 240 mg | Human RCTHuman clinicalHuman observationalAnimalIn-vitro |
| TUDCA (Tauroursodeoxycholic Acid) | Essentials II | 360 mg | Human RCTAnimalIn-vitro |
| Nattokinase | Essentials II | 120 mg | Human RCTHuman clinicalAnimalIn-vitro |
Quercetin and fisetin correction
Human studies exist.
Human senolysis is still unsettled.
The earlier animal-only labels were incomplete. These selected primary human studies justify human evidence badges, but their population, dose, formulation and endpoint boundaries remain attached.
Quercetin
Standalone human trials exist, while senolytic studies generally combine quercetin with dasatinib. Neither evidence stream proves that 300 mg quercetin in Essentials I clears senescent cells.
- Human RCT
Standalone quercetin: 150 mg/day for six weeks in 93 adults with overweight or obesity and metabolic-syndrome traits. Systolic blood pressure fell modestly; several other outcomes were unchanged or mixed. Senescent cells were not measured.
- Human RCT
Standalone quercetin: 500 mg/day for four weeks in a 22-person crossover trial. Plasma uric acid fell, while fasting glucose, urinary uric-acid excretion and resting blood pressure did not change. This was not a senolytic trial.
- Human RCT
Standalone quercetin: 500 mg/day for eight weeks after myocardial infarction. The 88-person trial found no significant effect on ICAM-1, VCAM-1 or depression versus placebo.
- Human clinical
A phase 1 dose-finding study gave quercetin to children and young adults with Fanconi anaemia. It supports human pharmacokinetic and tolerability knowledge in that specific population, not senolysis or healthy-aging efficacy.
- Human RCT · combination
Intermittent dasatinib plus quercetin was tested in 60 postmenopausal women. The primary 20-week bone-resorption endpoint was not improved; exploratory higher-burden subgroup findings require confirmation. The design cannot isolate quercetin.
Fisetin
Standalone human trials exist, including randomized disease-specific studies. The direct senescence-marker signal comes from a ten-person uncontrolled subgroup, and a 74-person knee-osteoarthritis trial reported null clinical results.
- Human RCT
Standalone fisetin: 100 mg/day for seven weeks in 37 people with colorectal cancer receiving chemotherapy. Of the measured inflammatory and matrix-remodelling markers, only IL-8 changed significantly versus placebo. Senescent-cell burden and aging outcomes were not tested.
- Human RCT · disease adjunct
Standalone fisetin: 100 mg/day for seven days alongside rt-PA in a 192-person acute-stroke trial. Reported neurological and biomarker findings are specific to an emergency disease-treatment context and do not test senolysis or aging; no prospective trial-registration identifier was identified in the paper.
- Human clinical · uncontrolled
Ten self-selected participants reporting 100 mg/day had longitudinal reductions in C12FDG-bright PBMCs and several serum markers. With no randomised control and a small subgroup, this is exploratory target-engagement evidence rather than proof of clinical benefit.
- Human RCT · registry results
A placebo-controlled knee-osteoarthritis study randomized 74 people and used intermittent approximately 20 mg/kg/day dosing. The registry posts results for safety, biomarkers, pain, function, gait and imaging; the conference report found no between-group clinical benefit. A full peer-reviewed results paper was not identified.
- Human RCT · conference report
The investigator conference report for the knee-osteoarthritis trial found no significant benefit for pain, function, strength, gait or cartilage MRI and no difference in adverse-event measures versus placebo.
Product boundary: amounts are per current labelled six-tablet serving of each individual formula. Evidence for an isolated ingredient, dose or population cannot be transferred automatically to Geroprotect®.
Chapter 01 · Origins
What nature makes possible.
Nature contains organisms with life histories far outside the human range. They are not promises of human immortality and they do not show that one mechanism can be copied into people. They are comparative experiments—clues to what evolution can tune.
Turritopsis dohrnii can, under stress or damage, move from an adult medusa through a cyst-like stage and return to a juvenile polyp. Adult-to-polyp reversal and transdifferentiation were documented experimentally in 1996; later genomic work explored how the programme is regulated. That repeated life-cycle reversal is why the species is often called “biologically immortal.” Individual jellyfish can still die from predation, disease or environmental failure.
The question that shaped Geroprotect is therefore narrower than immortality: which parts of human aging biology are measurable, which respond to behaviour or intervention, and where does the evidence stop?
Turritopsis dohrnii
Adult medusae have been observed returning to colonial polyps, with cell transdifferentiation involved in the reversal. It is a cnidarian developmental programme, not evidence that adult humans can reset their life cycle.
Original experimentNaked mole rat
A dataset of more than 3,000 captive animals reported no age-related rise in mortality hazard over the observed range—defying the textbook Gompertz pattern. The inference was challenged over the age structure of the data and remains debated.
Primary studyBowhead whale
Bowheads are estimated to live for more than two centuries. Comparative genomics has identified differences in DNA-repair, cell-cycle and cancer-related genes, but these associations do not establish a transferable human intervention.
Primary studyGreenland shark
Radiocarbon dating of eye-lens nuclei from 28 females placed the largest specimen at 392 ± 120 years and estimated sexual maturity at about 156 ± 22 years. The wide interval is part of the result, not a footnote.
Primary study“Ming” the ocean quahog
Growth-increment cross-dating revised this Arctica islandica specimen to 507 years. It did not survive collection and shell analysis—the uncomfortable reason its exceptional age could be established.
Primary chronologyAxolotl
Axolotls can regenerate limbs and repair parts of the spinal cord, retina and heart with far less scarring than mammals. This is a genuine vertebrate capability, but it does not imply equivalent latent regeneration in humans.
Research reviewMethuselah
The named Great Basin bristlecone pine germinated after writing was invented but before the Giza pyramids were built. Its quoted age advances with the calendar and remains approximate. Claims for older unnamed trees are kept separate because their status is disputed or unverified.
US Forest ServiceChapter 02 · A new age
Genome.
Epigenome.
The genome is the inherited DNA sequence. The epigenome is a changing layer of gene regulation—DNA methylation, histone marks and chromatin organisation among it. It records biology, but it is not a single master switch for aging.
McCay’s calorie-restriction experiment
McCay, Crowell and Maynard used restricted feeding to retard growth in rats. Males in the restricted groups had longer mean lifespan; the female mean was about the same across groups in the original report. This was an animal experiment—not a human lifespan result—and later work reframed calories rather than slowed growth as the central variable.
Read the paperThe Human Genome Project announces completion
The 14 April announcement delivered a high-quality reference covering about 92% of the genome, not a gapless sequence. It was a landmark map, but it did not identify a simple set of “aging genes” or explain how cells with largely the same inherited sequence develop very different identities.
NHGRI contextYamanaka reprograms mature mouse cells
Oct4, Sox2, Klf4 and c-Myc converted mouse fibroblasts to induced pluripotent stem cells. The 2012 Nobel Prize was shared by Shinya Yamanaka and John Gurdon for discoveries showing that mature cells can be reprogrammed. Full reprogramming is not an anti-aging treatment and carries loss-of-identity and tumour risks.
Read the paperHorvath’s multi-tissue methylation clock
Using 353 CpG sites across thousands of samples, the model correlated strongly with chronological age across many tissues and reported a median error of about 3.6 years. A clock estimates a methylation pattern; it does not by itself prove biological age, health improvement or added life.
Read the paperPartial reprogramming in progeroid mice
Ocampo and colleagues used cyclic OSKM expression in a premature-aging mouse model and reported improved age-associated features and longer survival. The study was not performed in normally aging humans, and its benefits and risks cannot be carried across species.
Read the paperOSK in the mouse eye
Lu and colleagues expressed Oct4, Sox2 and Klf4—without c-Myc—in mouse retinal ganglion cells. They reported restored methylation patterns, axon regeneration and improved vision in glaucoma-model and aged mice, with effects requiring TET1 and TET2. This is compelling preclinical work, not human vision restoration.
Read the paperThe last difficult sequence gaps close
The Telomere-to-Telomere Consortium published a gapless 3.055-billion-base-pair CHM13 reference, adding almost 200 million base pairs missing from earlier references. It completed a reference genome—not every person’s genome and not the explanation of aging.
Read the paperCALERIE measures pace, not lifespan
In a post-hoc analysis of a two-year randomized trial in 220 adults without obesity, a 25% calorie-reduction target produced roughly 12% achieved restriction. DunedinPACE indicated a modest 2–3% slowing in measured pace, while PhenoAge and GrimAge did not change significantly. These are surrogate biomarkers; the trial did not show longer life.
Read the paper
A hypothesis, not a verdict
The Information Theory of Aging
This theory interprets aging partly as a loss of regulatory or epigenetic information. It is influential and testable, but it is not established as the single cause of aging. DNA damage, epigenetic drift and the other hallmarks interact; movement on one clock cannot establish reversal of the whole system.
The human high-water mark
Rate may be modifiable. Lifespan is unproven.
No supplement or drug has been proven in a randomized trial to extend human lifespan. CALERIE supports the narrower conclusion that one methylation-derived pace measure responded modestly to sustained calorie restriction. It does not validate a supplement, a mortality benefit or the claim that aging has been reversed.
Chapter 03 · The framework
12 canonical.
2 emerging.
The 2023 Cell framework names twelve canonical hallmarks. Splicing dysregulation and altered mechanical properties are shown separately as credible published extensions—not quietly promoted to canonical status.
“Researched in relation to” describes a study connection—not proof that an ingredient corrects a hallmark, that the two finished formulas reproduce an isolated-compound result, or that either formula extends human life. Human RCT, observational, animal and mechanistic evidence are not interchangeable.
Genomic instability
DNA lesions, chromosome errors and impaired repair accumulate with age. Oxidative stress is one contributor to this damage; it is not a separate canonical hallmark.
Ingredients researched in relation to this process
Evidence tierMechanistic and preclinical
Evidence gapNo human trial shows that the finished formulas reduce genomic instability or extend lifespan.
Telomere attrition
Telomeres protect chromosome ends. In many dividing human cells they shorten with replication and damage, eventually contributing to senescence or loss of function.
Ingredients researched in relation to this process
Evidence tierIndirect human and preclinical research only
Evidence gapNeither formula contains a proven telomerase intervention; antioxidant research is not direct evidence of telomere preservation.
Epigenetic alterations
Age is associated with changes in DNA methylation, histone marks, chromatin organisation and gene regulation. Epigenetic clocks measure patterns; they are not validated proof of rejuvenation.
Ingredients researched in relation to this process
Evidence tierMechanistic, animal and limited human-surrogate research
Evidence gapThe reported Ca-AKG clock study was uncontrolled and commercially associated; clock change is not a lifespan endpoint.
Loss of proteostasis
Protein synthesis, folding, trafficking and disposal become less reliable, allowing damaged or misfolded proteins to accumulate.
Ingredients researched in relation to this process
Evidence tierPreclinical and disease-context research
Evidence gapThere is no human healthy-aging trial of the finished formulas for proteostasis. Withaferin A evidence is preparation-specific and largely preclinical, so it does not establish a finished-formula effect.
Disabled macroautophagy
Macroautophagy is a cellular recycling programme. With age, impaired clearance can leave damaged proteins and organelles behind; mitophagy is the mitochondria-specific branch.
Ingredients researched in relation to this process
Evidence tierHuman functional and preclinical research
Evidence gapUrolithin A has human functional data, but that does not show that this formula slows aging or extends human life.
Deregulated nutrient-sensing
Insulin–IGF-1, mTOR, AMPK and sirtuin-linked networks help cells match growth and maintenance to nutrient availability. Their balance changes with age and metabolic state.
Ingredients researched in relation to this process
Evidence tierHuman metabolic or surrogate data plus preclinical research
Evidence gapMetabolic biomarker changes are not evidence of slower aging. Berberine has clinically relevant interaction potential.
Mitochondrial dysfunction
Mitochondrial quality control, signalling and energy production change with age. Reactive oxygen species are part of this network, not a stand-alone canonical hallmark.
Ingredients researched in relation to this process
Evidence tierHuman functional or disease-specific data plus preclinical research
Evidence gapEvidence for an ingredient or a disease population cannot be transferred to the 26-active system or to general longevity.
Cellular senescence
Senescent cells stop dividing and can develop a pro-inflammatory secretory phenotype. Senescence also has useful roles in wound healing and tumour suppression, so context matters.
Ingredients researched in relation to this process
Evidence tierCell and animal research plus early human intervention studies
Evidence gapStandalone quercetin and fisetin trials have measured condition-specific outcomes, but they do not establish human senolysis. Senolytic studies remain small or exploratory, often use drug combinations, and do not validate this finished formula.
Stem cell exhaustion
The number, fitness or regenerative capacity of tissue stem cells can decline, limiting maintenance and repair.
Ingredients researched in relation to this process
Evidence tierAnimal and mechanistic research
Evidence gapThere is no robust human evidence that these ingredients restore stem-cell reserves or tissue regeneration in healthy adults.
Altered intercellular communication
Endocrine, neuronal, immune and local tissue signals become less coordinated, changing how organs maintain homeostasis together.
Ingredients researched in relation to this process
Evidence tierMixed human-surrogate, observational and preclinical research
Evidence gapBlood-pressure, inflammatory or observational outcomes do not demonstrate repair of intercellular communication. Nattokinase changes fibrinolysis markers, but clinical bleeding risk at the labelled amount is not established; medicines and procedures still warrant professional review.
Chronic inflammation
Persistent, low-grade inflammatory signalling—often called inflammaging—can disrupt tissue function and reinforce other hallmarks.
Ingredients researched in relation to this process
Evidence tierHuman biomarker and preclinical research; results are mixed
Evidence gapChanges in inflammatory biomarkers are not proof of disease prevention or lifespan extension, and formulation and dose materially affect results.
Dysbiosis
Age-related shifts in microbial communities and host–microbe signalling can affect immunity and metabolism. Cause and consequence are difficult to separate.
Ingredients researched in relation to this process
Evidence tierPreclinical and limited human mechanistic research
Evidence gapUrolithin A is a microbial metabolite and natural production varies, but direct supplementation has not been shown to correct dysbiosis or slow human aging.
Splicing dysregulation
Errors and age-related shifts in RNA processing can change which protein isoforms a cell produces. This is a published candidate extension, not one of the canonical twelve.
Evidence tierEmerging mechanistic field
Evidence gapNo Geroprotect active has a defensible direct mapping here; the gap is intentional and visible.
Altered mechanical properties
Extracellular-matrix remodelling, cross-linking and tissue stiffening alter the physical environment in which cells function. This is an emerging extension, not a canonical 2023 hallmark.
Evidence tierEmerging mechanistic field
Evidence gapIndirect antioxidant or metabolic research is not a direct ECM intervention; the current formulas have no proven answer here.
Chapter 04 · Our mission
Build for the long game.
State the limits.
Geroprotect is a Nutrae brand. W. T. van Dieten leads its formulation and editorial direction, working with collaborators in Europe, doctors and chemists in Shanghai, and quality and manufacturing partners in the UAE. Our wider work spans Nutrae, Geroprotect and Peakspan; Geroprotect is the product brand discussed on this page.
Geroprotect® contains 26 actives across two formulas—13 in Essentials I and 13 in Essentials II—with each amount stated. There are no proprietary-blend totals. That compositional transparency is not the same as clinical validation: the complete two-formula system has not been tested for slowing aging or extending lifespan in humans.
Our responsibility is to separate what is known, what is plausible and what remains unknown. Some ingredients have randomized human data for functional, metabolic or disease-specific endpoints. Others rest on observational, animal or cell evidence. Where the direct answer is “none yet,” we publish the gap.
Human evidence is endpoint-specific
An RCT can support the outcome it measured—not a broader claim. Urolithin A functional results, NMN or NR surrogate results and disease-specific CoQ10 outcomes do not establish human lifespan extension.
Preclinical is not clinical
Cell and animal studies are valuable for mechanism and prioritisation. They cannot be written as if the same effect has occurred in people, at the formula dose, or in the finished combination.
Clocks are biomarkers
DNA-methylation clocks can estimate age-linked patterns or pace. Different clocks can disagree, and they are not validated surrogate endpoints for living longer.
Funding and conflicts matter
Some Ca-AKG, urolithin A and C15:0 studies have commercial sponsorship, patents or author conflicts. That does not make a result false; it makes independent replication and careful wording essential.
Interaction flags
Evidence includes
safety.
This summary is intentionally visible. It is not exhaustive and does not replace the current label, a pharmacist or a clinician who knows your medicines and health history.
Medicines and procedures
Essentials II lists 120 mg nattokinase and 360 mg fucoidan per labelled serving. Nattokinase affects fibrinolysis, while fucoidan shows anticoagulant activity mainly in laboratory studies. Oral human data have not established a clinically meaningful bleeding rate at these amounts or for their combination. As a precaution, anyone using anticoagulant or antiplatelet medicines, or preparing for a procedure, should ask their clinician before use.
Metabolism and drug transport
Repeated berberine dosing altered CYP2D6, CYP2C9 and CYP3A4 activity in a human study and may interact with P-glycoprotein substrates; it can also add to glucose-lowering effects. Quercetin interaction evidence is less certain and is largely mechanistic.
Liver signals need precise wording
Concentrated green-tea extracts have a recognised liver-injury signal, particularly at high exposure and when fasted. Published liver-injury cases involve ashwagandha products; they cannot be automatically attributed to purified withaferin A at this dose, but they justify caution rather than silence.
Context changes risk
Genistein is estrogenic and may be unsuitable in some hormone-sensitive or thyroid contexts. In one small, short pterostilbene study, LDL cholesterol rose in both monotherapy arms and the 100 mg/day and 250 mg/day estimates were similar. Total intake, other supplements, medicines, pregnancy, liver disease and planned surgery all matter.
Mechanism correction
Resveratrol and SIRT1
Early claims that resveratrol directly activates SIRT1 were challenged when some effects proved dependent on the fluorescent assay substrate. That weakens a simple direct-activation story; it does not mean every reported biological action of resveratrol has been disproved. Normal-diet mouse lifespan testing was also null.
Commercial disclosure
We sell what we discuss.
Geroprotect has a commercial interest in the ingredients and formulas described here. Ingredient studies are cited so readers can inspect population, dose, endpoint, funding and limitations. Discussion of an ingredient is not proof for Geroprotect®.
Our standard
Aging is not a clock you can stop. On the evidence, it is a rate you can change. Set it deliberately.
Here, “rate” means measured aspects of aging biology and pace biomarkers that can respond to behaviour or intervention—not a promise of age reversal. No supplement or drug has been proven in a randomized trial to extend human lifespan.
Reviewed 14 July 2026
Sources you can
inspect.
Links point to primary papers or authoritative project sources where available. Evidence tiers describe the cited study, not the finished Geroprotect formulas. This page will be re-reviewed as stronger human evidence or safety information becomes available.
- 01López-Otín et al. (2013), The hallmarks of aging.
Original nine-hallmark framework; Cell 153:1194–1217.
- 02López-Otín et al. (2023), Hallmarks of aging: an expanding universe.
Canonical twelve-hallmark update; Cell 186:243–278.
- 03Schmauck-Medina et al. (2022), New hallmarks of ageing.
Copenhagen meeting summary proposing candidate extensions including splicing and altered mechanical properties.
- 04Piraino et al. (1996), Reversing the life cycle in Turritopsis.
Laboratory documentation of adult medusae transforming into juvenile polyps through a resting stage; Biological Bulletin.
- 05Pascual-Torner et al. (2022), Comparative genomics of mortal and immortal cnidarians.
Later genomic study of life-cycle reversal in Turritopsis dohrnii; PNAS.
- 06Ruby, Smith & Buffenstein (2018), Naked mole-rat mortality rates defy Gompertzian laws.
Analysis of more than 3,000 captive-animal records; eLife.
- 07Dammann et al. (2019), Comment on naked mole-rat mortality data.
Published challenge about age distribution and inference; eLife.
- 08Keane et al. (2015), Insights into the evolution of longevity from the bowhead whale genome.
Comparative genomics of a mammal estimated to live beyond 200 years; Cell Reports.
- 09Nielsen et al. (2016), Eye lens radiocarbon reveals centuries of longevity in the Greenland shark.
Twenty-eight females; largest estimate 392 ± 120 years; Science.
- 10Butler et al. (2013), Variability of marine climate from Arctica islandica growth increments.
Shell chronology that established the 507-year specimen; Palaeogeography, Palaeoclimatology, Palaeoecology.
- 11Joven, Elewa & Simon (2019), Model systems for regeneration: salamanders.
Research review covering salamander tissue regeneration and its biological limits.
- 12US Forest Service, Pinus longaeva species review.
Authoritative background on Great Basin bristlecone pine longevity and Methuselah.
- 13Nurk et al. (2022), The complete sequence of a human genome.
Telomere-to-Telomere CHM13 reference; Science.
- 14Horvath (2013), DNA methylation age of human tissues and cell types.
The 353-CpG multi-tissue clock; Genome Biology.
- 15Takahashi & Yamanaka (2006), Induction of pluripotent stem cells by defined factors.
Four-factor reprogramming in mouse fibroblasts; Cell.
- 16Ocampo et al. (2016), In vivo amelioration of age-associated hallmarks by partial reprogramming.
Cyclic OSKM in progeroid mice; Cell.
- 17Lu et al. (2020), Reprogramming to recover youthful epigenetic information and restore vision.
OSK in mouse retinal ganglion cells and mouse models; Nature.
- 18McCay, Crowell & Maynard (1935), The effect of retarded growth upon life span.
Foundational calorie-restriction experiment in rats; Journal of Nutrition.
- 19Waziry et al. (2023), Caloric restriction and DNA-methylation measures in CALERIE.
Post-hoc analysis of a two-year, 220-person randomized trial; Nature Aging.
- 20Singh et al. (2022), Urolithin A and muscle endurance in older adults.
Randomized human functional study; Cell Reports Medicine.
- 21Yoshino et al. (2021), NMN and muscle insulin sensitivity in prediabetic women.
Small randomized human surrogate-endpoint study; Science.
- 22Egert et al. (2009), quercetin in adults with metabolic-syndrome traits.
Standalone 150 mg/day randomized crossover trial; modest systolic-blood-pressure result, with mixed or null findings across other outcomes. Not a senolytic trial.
- 23Shi & Williamson (2016), quercetin and plasma uric acid.
Standalone 500 mg/day randomized crossover trial in 22 men; endpoint-specific human evidence, not evidence of senescent-cell clearance.
- 24Dehghani et al. (2023), quercetin after myocardial infarction.
Standalone 500 mg/day randomized trial; ICAM-1, VCAM-1 and depression outcomes were not significantly different from placebo.
- 25Mehta et al. (2025), phase 1 quercetin in Fanconi anaemia.
Human dose-finding, pharmacokinetic and tolerability evidence in a specific rare-disease population; not healthy-aging or senolytic efficacy evidence.
- 26Farr et al. (2024), intermittent dasatinib plus quercetin and bone metabolism.
Sixty-person phase 2 randomized trial; the primary endpoint was null and the combination design cannot isolate quercetin.
- 27Farsad-Naeimi et al. (2018), fisetin during colorectal-cancer chemotherapy.
Standalone 100 mg/day randomized trial in 37 people; only IL-8 differed significantly from placebo among the measured markers. Senolysis was not tested.
- 28Wang et al. (2019), fisetin alongside rt-PA after acute stroke.
Standalone 100 mg/day randomized trial in an emergency disease-treatment context; not evidence for senolysis, healthy aging or the Geroprotect formula. No prospective registration identifier was identified in the paper.
- 29Hambright et al. (2024), C12FDG and senescence-associated phenotypes.
Exploratory longitudinal analysis of ten self-selected fisetin users; uncontrolled target-engagement signal, not proof of clinical benefit.
- 30NCT04210986, randomized fisetin trial in knee osteoarthritis.
ClinicalTrials.gov posts participant flow, adverse events and outcome results for 74 randomized participants. Full peer-reviewed results paper not identified.
- 31Tashman et al. (2025), randomized fisetin trial in knee osteoarthritis.
Conference results report: no between-group benefit for the tested pain, function, strength, gait or cartilage-MRI outcomes.
- 32Guo et al. (2012), Repeated berberine administration inhibits cytochromes P450 in humans.
Human crossover interaction study; European Journal of Clinical Pharmacology.
- 33Yu et al. (2022), Green-tea extract, liver enzymes and genetic variation.
Randomized-trial safety analysis at high supplemental exposure.
- 34Björnsson et al. (2020), Liver injury due to ashwagandha.
Case series involving ashwagandha products—not direct evidence for purified withaferin A.
- 35Pacholec et al. (2010), Sirtuin compounds and resveratrol are not direct activators of SIRT1.
Assay-dependence challenge; Journal of Biological Chemistry.
The six pathways
How the science meets the formula
Each pathway below is one of the six on the home page. For each one: what the biology actually describes, where the human evidence stops, and which named actives in Essentials I and Essentials II engage it. Amounts for every active are published in the supplement facts table; the wider framework is set out in the hallmarks of aging.
Cellular defence
Supports natural antioxidant pathways and everyday cellular resilience.
What the biology describes
Cells live under constant chemical pressure — normal metabolism alone produces reactive molecules faster than they can be ignored. The body answers with its own defence machinery, a set of enzymes it makes on demand rather than a stock of antioxidants it holds in reserve. Much of the laboratory interest in dietary polyphenols is about this response: not the molecules mopping up damage themselves, but whether they nudge the cell to switch its own defences on. That distinction matters, and it is also where the evidence is strongest in cells and thinnest in people.
How our formulas engage it
Both formulas carry a group of actives grouped around this response. Essentials I contributes curcumin and pterostilbene; Essentials II contributes EGCG, luteolin and baicalein. They are named individually on the label, in stated amounts, because a defence claim you cannot audit is not worth making.
Where it stops. Most of the mechanistic work here is preclinical. Human trials on these compounds measure biomarkers, not lifespan.
Cellular maintenance
Supports pathways associated with NAD+ metabolism and DNA maintenance.
What the biology describes
NAD⁺ is a coenzyme every cell needs to convert fuel into usable energy, and it is also the currency spent by two families of repair and signalling enzymes — the sirtuins and the PARPs — that act when DNA is damaged. Tissue NAD⁺ levels fall with age in several species, including humans, which is why precursors that raise it have been studied so heavily. Human trials do consistently show that oral precursors raise blood NAD⁺. What they have not yet shown is that raising it changes how a person ages.
How our formulas engage it
Essentials I supplies NMN alongside apigenin and quercetin. Essentials II supplies nicotinamide riboside with resveratrol. The renewal side of maintenance — the cell's own clearing-out of damaged components — is where spermidine and fisetin sit.
Where it stops. Raising a biomarker is not the same as changing an outcome. We report the first and do not claim the second.
Mitochondrial support
Supports cellular energy systems and everyday vitality.
What the biology describes
Mitochondria generate most of the ATP a cell spends, and their decline is one of the hallmarks of aging that has held up best under scrutiny. The interesting variable is not only how many mitochondria a cell has but how well it retires the failing ones — a recycling process called mitophagy. This is one of the few areas where a longevity-adjacent compound has been through properly controlled human trials with a functional endpoint rather than a biomarker.
How our formulas engage it
Essentials I carries urolithin A, CoQ10 and PQQ. Essentials II adds L-ergothioneine and pentadecanoic acid (C15:0), which concern the membrane side of the same system.
Where it stops. Endpoints in the published human work are muscle-function and biomarker measures in defined populations, not general claims about energy.
Inflammatory balance
Supports the body’s normal inflammatory response.
What the biology describes
Inflammation is not the problem; it is the repair signal. The observation behind this pathway is narrower and better evidenced: across large populations, low-grade inflammatory signalling tends to drift upward with age even without infection or injury, and that drift tracks with other measures of biological aging. The research question is whether diet-derived compounds influence the normal regulation of that signalling — keeping the response proportionate, not suppressing it.
How our formulas engage it
Essentials I contributes curcumin and fisetin; Essentials II contributes luteolin, baicalein and genistein.
Where it stops. Nothing here is an anti-inflammatory medicine, and none of it is a substitute for one. If you are being treated for an inflammatory condition, that is a conversation for your doctor.
Metabolic balance
Supports efficient energy use and normal metabolic function.
What the biology describes
Cells constantly read how much fuel is available and switch between building and recycling accordingly — the nutrient-sensing machinery, including AMPK and mTOR, that calorie-restriction research has circled for ninety years. It is the hallmark with the longest experimental history and the clearest animal data, and it is also the one where translating from animals to people has proved hardest: the human trials measure the pace of change, not lifespan.
How our formulas engage it
Essentials I is where this group sits: calcium alpha-ketoglutarate, berberine and 5-aminolevulinic acid, each named on the label rather than hidden inside a blend.
Where it stops. These are studied in relation to normal metabolic function in healthy people. They are not a treatment for any metabolic condition, and berberine in particular can interact with prescribed medicines — check with your doctor first.
Antioxidant support
Helps the body manage oxidative stress.
What the biology describes
Oxidative stress is the imbalance between reactive species produced and the body's capacity to neutralise them. The naive version of this idea — flood the system with antioxidants and slow aging — was tested at scale and did not hold; several large trials of high-dose single antioxidants showed no benefit. What survived is more specific: certain compounds interact with the body's own regulatory systems rather than substituting for them, and dose and context decide whether the effect is useful.
How our formulas engage it
Essentials I contributes quercetin and pterostilbene; Essentials II contributes EGCG, resveratrol and L-ergothioneine.
Where it stops. We say "helps the body manage" rather than "eliminates" on purpose — the failed megadose trials are part of this evidence base, not a footnote to it.
These statements have not been evaluated by MOHAP and are not intended to diagnose, treat, cure or prevent any disease. Food supplements are not a substitute for a varied diet or medical advice.
