PEER-REVIEWED SCIENTIFIC FOUNDATION
Every reference below is a real, independently published paper. Each entry is source-linked to PubMed and, where available, to its DOI record, so any claim can be traced to the original literature in one click.
Literature reviewed through 2026 · Grading applied by the LONGEVILABS scientific team · Corrections welcome
Independent peer-reviewed literature indexed across:
Frontiers in Genetics · The Journals of Gerontology: Series A · GeroScience · npj Aging and Mechanisms of Disease · Antioxidants · Nutrients · American Journal of Clinical Nutrition · EBioMedicine · Alternative Therapies in Health and Medicine · Journal of Agricultural and Food Chemistry · Nutrition · Journal of the American Heart Association
30 verified public references
Biological age · Epigenetics
Johnson AA, Sinclair DA
Frontiers in Genetics · 2026 · Systematic review · 41 human intervention studies
Finding
Several interventions were reported to decrease one or more epigenetic-age measures.
Limitation
Epigenetic clocks remain investigational biomarkers and studies were heterogeneous.
Biological age · Epigenetics
Chen L, Dong Y, Bhagatwala J, Raed A, Huang Y, Zhu H
The Journals of Gerontology: Series A · 2019 · Randomized clinical trial · 70 randomized; DNA-methylation analysis in 51
Finding
The 2,000 IU/day arm showed a 1.90-year Hannum difference versus placebo; 4,000 IU/day showed a 1.85-year Horvath difference.
Limitation
Small secondary analysis; authors called for larger, longer trials and the Hannum result was not conclusive.
NAD+ · Epigenetics
Orr ME et al.
GeroScience · 2024 · Randomized placebo-controlled pilot · 20 older adults
Finding
Blood NAD+ increased 2.6-fold; DNA methylation was explored.
Limitation
Small pilot; methylation was exploratory and NAD+ is not a biological-age clock.
NAD+
Dellinger RW et al.
npj Aging and Mechanisms of Disease · 2017 · Randomized double-blind placebo-controlled trial · 120 adults aged 60–80
Finding
Dose-dependent, sustained increases in whole-blood NAD+ were reported.
Limitation
Combination intervention; does not establish biological-age reduction.
Biological age
Félix J et al.
Antioxidants · 2024 · Randomized controlled trial · 41 adults aged 30–63
Finding
Investigators reported an approximately 11-year decrease in calculated immune biological age.
Limitation
Three-component intervention; result cannot be attributed to spermidine alone and is not chronological-age reversal.
Telomeres
de Jaeger C et al.
Nutrients · 2024 · Randomized double-blind placebo-controlled trial · 40 healthy adults
Finding
Longer median and short-telomere length and fewer very short telomeres were reported versus placebo.
Limitation
A specific formulation was tested; telomere length is not epigenetic age.
Telomeres
VITAL Telomere Substudy investigators
American Journal of Clinical Nutrition · 2025 · Randomized controlled trial substudy · VITAL telomere substudy
Finding
The study evaluated whether supplementation affected telomere attrition over four years.
Limitation
Telomere length is one biomarker and is not equivalent to whole-body rejuvenation.
Senescence
Hickson LJ et al.
EBioMedicine · 2019 · Open-label pilot study · 9 participants with diabetic kidney disease
Finding
Markers of senescent-cell burden decreased after the drug-plus-quercetin intervention.
Limitation
Very small, uncontrolled drug combination; cannot be attributed to quercetin or extrapolated to healthy adults.
Biological age · Senescence
Lee E, Burns M
Alternative Therapies in Health and Medicine · 2024 · Pilot study · Pilot population
Finding
Pilot observations were reported for biological-aging measures.
Limitation
Preliminary pilot evidence; requires independent, controlled replication.
Epigenetics
Clarke JD et al.
Journal of Agricultural and Food Chemistry · 2011 · Human crossover feeding study · Human volunteers
Finding
Sprouts produced greater, earlier metabolite exposure; lower PBMC HDAC activity was observed only after sprouts.
Limitation
Evidence of epigenetic activity, not biological-age reversal; source and myrosinase materially affected exposure.
Epigenetics · Metabolic
Fan L et al.
Nutrition · 2021 · Human intervention analysis · Human participants
Finding
Magnesium treatment was associated with locus-specific methylation changes.
Limitation
A gene-specific methylation signal is not an epigenetic-age clock.
Telomeres · Mitochondria
Opstad TB et al.
Nutrients · 2022 · Randomized placebo-controlled substudy · Older Swedish adults
Finding
The combination was associated with less telomere attrition.
Limitation
Combination study; effect cannot be assigned to CoQ10 alone.
Quercetin Dihydrate · Metabolic
Serban MC et al.
Journal of the American Heart Association · 2016 · Systematic review and meta-analysis of RCTs · Pooled randomized trials in adults
Finding
Pooled analysis reported significant reductions in systolic and diastolic blood pressure with quercetin supplementation.
Limitation
Cardiometabolic endpoint; blood pressure is not a measure of biological age.
Quercetin Dihydrate · Metabolic · Senescence
Ou Q et al.
Phytotherapy Research · 2023 · Umbrella review of meta-analyses · Multiple pooled randomized trials
Finding
Across meta-analyses, quercetin was associated with favourable changes in several cardiometabolic markers.
Limitation
Effect sizes varied by dose, duration and population.
Spermidine · Biological age
Schwarz C, Benson GS, Horn N et al.
JAMA Network Open · 2022 · Randomized clinical trial (SmartAge) · 100 older adults with subjective cognitive decline
Finding
Twelve-month supplementation was safe and well tolerated; no significant memory benefit versus placebo was detected.
Limitation
Null primary outcome; underlines that autophagy signalling does not automatically translate into clinical endpoints.
Spermidine · Biological age
Wirth M, Benson G, Schwarz C et al.
Cortex · 2018 · Randomized controlled pilot trial · 30 older adults at risk for dementia
Finding
Supplementation was well tolerated and showed preliminary signals on memory performance.
Limitation
Very small pilot; findings were not confirmed in the larger SmartAge trial.
Berberine HCl · Metabolic
Yin J, Xing H, Ye J
Metabolism · 2008 · Randomized human trials · Adults with type 2 diabetes
Finding
Berberine produced clinically meaningful improvements in glucose and lipid parameters.
Limitation
Clinical diabetes population; not a healthy-ageing or biological-age endpoint.
Sulforaphane System · Metabolic · Epigenetics
Axelsson AS et al.
Science Translational Medicine · 2017 · Randomized placebo-controlled trial with preclinical work · 97 adults with type 2 diabetes
Finding
Sulforaphane reduced hepatic glucose production and improved fasting glucose in obese, dysregulated participants.
Limitation
Benefit was concentrated in a dysregulated subgroup; healthy-adult effects are unproven.
Trans-Resveratrol · Metabolic · Mitochondria
Timmers S et al.
Cell Metabolism · 2011 · Randomized double-blind crossover trial · 11 healthy obese men
Finding
Resveratrol activated AMPK/SIRT1 signalling and improved muscle mitochondrial respiration and metabolic markers.
Limitation
Small crossover study in obese men; short duration.
Trans-Resveratrol · Metabolic
García-Martínez BI et al.
Medicina Clínica · 2022 · Systematic review and meta-analysis · Pooled randomized trials
Finding
Pooled data suggested improvements in selected glycaemic parameters.
Limitation
Heterogeneous doses and formulations; bioavailability differs by preparation.
Nicotinamide Riboside · NAD+
Martens CR et al.
Nature Communications · 2018 · Randomized double-blind placebo-controlled crossover trial · 30 healthy middle-aged and older adults
Finding
NAD+ increased about 60% and the intervention was well tolerated; exploratory blood-pressure signals were reported.
Limitation
Small crossover trial; cardiovascular endpoints were exploratory.
Pterostilbene · Metabolic
Riche DM et al.
Journal of Toxicology · 2013 · Randomized double-blind placebo-controlled trial · 80 adults
Finding
Pterostilbene was generally well tolerated at the doses studied.
Limitation
Primarily a safety analysis, not an efficacy or ageing endpoint.
Magnesium Glycinate · Metabolic
Song Y, He K, Levitan EB, Manson JE, Liu S
Diabetic Medicine · 2006 · Meta-analysis of randomized double-blind trials · Pooled adults with type 2 diabetes
Finding
Magnesium supplementation was associated with reduced fasting glucose.
Limitation
Diabetes population; magnesium status at baseline strongly influences response.
Magnesium Glycinate · Metabolic
Asbaghi O, Moradi S, Kashkooli S et al.
British Journal of Nutrition · 2022 · Systematic review and dose-response meta-analysis · Pooled controlled clinical trials
Finding
Dose-response analysis reported improvements in several glycaemic markers.
Limitation
Trial quality and magnesium salt forms varied.
Vitamin D3 · Biological age
Manson JE et al.
New England Journal of Medicine · 2019 · Large randomized placebo-controlled trial · 25,871 adults
Finding
Supplementation did not lower the incidence of the primary endpoints in this generally replete population.
Limitation
A disease-prevention endpoint; it does not address biological-age biomarkers such as methylation clocks.
Vitamin K2 MK-7 · Metabolic
Knapen MHJ et al.
Thrombosis and Haemostasis · 2015 · Randomized double-blind placebo-controlled trial · 244 healthy postmenopausal women
Finding
Long-term MK-7 improved arterial stiffness indices versus placebo.
Limitation
Single population (postmenopausal women); vascular endpoint only.
Coenzyme Q10 · Mitochondria
Alehagen U, Johansson P, Björnstedt M, Rosén A, Dahlström U
International Journal of Cardiology · 2013 · Randomized double-blind placebo-controlled trial · 443 elderly Swedish citizens
Finding
The combination was associated with reduced cardiovascular mortality and lower NT-proBNP over follow-up.
Limitation
Combination intervention in a selenium-poor population; CoQ10 alone cannot be isolated.
Alpha-Lipoic Acid · Metabolic
Akbari M, Ostadmohammadi V, Lankarani KB et al.
Metabolism · 2018 · Systematic review and meta-analysis · Pooled randomized controlled trials
Finding
Supplementation was associated with improvements in fasting glucose, insulin resistance and selected lipid markers.
Limitation
Metabolic-disease populations; healthy-adult and ageing endpoints were not assessed.
Alpha-Lipoic Acid · Metabolic
Ziegler D et al.
Diabetes Care · 2006 · Randomized double-blind placebo-controlled trial · 181 adults with diabetic polyneuropathy
Finding
Oral alpha-lipoic acid improved neuropathic symptoms, with 600 mg/day offering the best benefit–risk profile.
Limitation
Clinical neuropathy population; short duration.
Astragalus Root Extract · Telomeres
Fernandez ML et al.
Current Pharmaceutical Design · 2018 · Randomized double-blind placebo-controlled trial · Adults with metabolic syndrome
Finding
Investigators reported improvements in selected cardiovascular markers versus placebo.
Limitation
Specific proprietary extract; results do not transfer automatically to other Astragalus preparations.
LONGEVILABS EVIDENCE INDEX™
Multiple well-designed controlled human studies or high-quality synthesis.
At least one controlled human study with relevant biological outcomes.
Early, observational, or indirect human evidence supported by mechanism.
Cellular or animal models; not evidence of a human clinical outcome.
Biologically plausible hypothesis requiring substantive validation.