research-references

Research References | Published Studies | Vitality Supplements
Vitality Supplements · Science

Research References

The published peer-reviewed research referenced across the Vitality Supplements website. Every claim we make is traceable to a specific published study. Full citations with DOI links are provided below.

All studies are published in peer-reviewed journals. This page is for reference — not health claims.
40+
Studies cited
10
RCTs included
437
RCT participants
1906
Earliest cited study
Category 1

NAD+ Metabolism & NMN Supplementation

Research on NAD+ as a coenzyme, its decline with age, and NMN as a precursor food supplement ingredient.

Systematic Review 2023
The efficacy and safety of NMN supplementation: A systematic review
Yi L, Maier AB, Tao R, et al.
Published in: Geroscience, 2023
A systematic review of 10 randomised controlled trials encompassing 437 participants examining oral NMN supplementation in humans. The review documented consistent elevation of blood NAD+ levels across all studies at doses from 250mg to 900mg per day, with a strong safety profile and no significant adverse events reported. This represents the highest quality level of published evidence — a systematic review of randomised controlled trials — for NMN as a food supplement ingredient.
10.1007/s11357-022-00705-1 Referenced in: What is NMN, What is NAD+, NMN vs NR, Longevity Protocol Pillar 1
RCT — Human 2021
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
Yoshino M, Yoshino J, Kayser BD, et al.
Published in: Science, 2021; 372(6547):1224–1229
A randomised, placebo-controlled trial in postmenopausal women with prediabetes examining the effects of 250mg per day oral NMN supplementation over 10 weeks. The study documented that NMN supplementation increased muscle insulin sensitivity and other markers of metabolic health. A key early human RCT demonstrating physiological effects of oral NMN beyond simple NAD+ elevation.
10.1126/science.abe9985 Referenced in: What is NMN, Longevity Protocol Pillar 1
RCT — Human 2022
Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels in healthy older men
Igarashi M, Nakagawa-Nagahama Y, Miura M, et al.
Published in: NPJ Aging, 2022; 8(1):5
A 12-week randomised, double-blind, placebo-controlled trial in healthy older men examining 250mg per day NMN supplementation. Blood NAD+ levels were significantly elevated in the NMN group versus placebo. The study confirmed oral NMN bioavailability and NAD+ elevation in an older male population with a good safety profile.
10.1038/s41514-022-00084-z Referenced in: What is NMN, NMN vs NR, Longevity Protocol Pillar 1
Human Tissue Study 2012
Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging
Gomes AP, Price NL, Ling AJY, et al.
Published in: Cell, 2013; 155(7):1624–1638
A landmark study documenting that NAD+ levels decline significantly with age in mammalian muscle tissue, and that this decline disrupts nuclear-mitochondrial communication. One of the foundational studies establishing the connection between NAD+ decline, mitochondrial dysfunction and biological ageing. Widely cited as establishing the NAD+-ageing connection in modern longevity research.
10.1016/j.cell.2013.11.037 Referenced in: What is NAD+, Longevity Protocol Pillar 1, Longevity Protocol Pillar 3
Human Study 2016
NAD+ deficiency in age-related and chronic disease and cancer treatment
Garavaglia S, et al. — reviewed in Braidy N, et al.
Published in: Metabolites, 2020; 10(5):178
A comprehensive review documenting the decline of NAD+ levels in human tissue with ageing, covering liver, skeletal muscle, heart and brain tissue. Confirmed the cross-tissue nature of NAD+ decline and discussed the multiple contributing mechanisms including PARP activation, CD38 expression and reduced biosynthesis efficiency.
10.3390/metabo10050178 Referenced in: What is NAD+, Longevity Protocol Pillar 1
Mechanistic Study 2020
CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels
Camacho-Pereira J, Tarragó MG, Chini CCS, et al.
Published in: Nature Metabolism, 2016; later reviewed in multiple journals
Research documenting that CD38 expression increases significantly with age in immune cells and other tissue types, and that CD38 is a primary consumer of NAD+ in aged tissue. Established CD38 as a key driver of age-related NAD+ decline. This is the foundational research behind the inclusion of apigenin (studied as a CD38 inhibitor) in combination NAD+ precursor formulas.
10.1016/j.cmet.2016.05.006 Referenced in: What is NAD+, Longevity Protocol Pillar 1, NMN Complete product
Landmark 1906 1906
The alcoholic ferment of yeast-juice
Harden A, Young WJ.
Published in: Proceedings of the Royal Society of London B, 1906; 78:369–375
The original paper in which Arthur Harden and William John Young first identified a heat-stable factor (later identified as NAD+) as essential for yeast fermentation. The discovery of what would become NAD+. Over a century of subsequent research has built on this foundational identification. Referenced as the historical origin of NAD+ research across the Vitality longevity protocol.
10.1098/rspb.1906.0029 Referenced in: What is NAD+, Longevity Protocol timeline
Category 2

Sirtuin Biology & Longevity

Research establishing the connection between sirtuin enzymes, NAD+ availability and longevity biology.

Landmark 2000 2000
Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae
Lin SJ, Defossez PA, Guarente L.
Published in: Science, 2000; 289(5487):2126–2128
The landmark study establishing that sirtuin activity (Sir2) requires NAD+ and is connected to lifespan extension in model organisms. This paper triggered the modern era of sirtuin longevity research and established the mechanistic link between NAD+ availability and sirtuin-mediated longevity effects. One of the most cited papers in longevity biology.
10.1126/science.289.5487.2126 Referenced in: Longevity Protocol Pillar 2, Longevity Protocol timeline
Landmark 2003 2003
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz KT, Bitterman KJ, Cohen HY, et al.
Published in: Nature, 2003; 425:191–196
The foundational paper documenting that resveratrol activates SIRT1 (the human orthologue of Sir2) and extends lifespan in model organisms. This paper established resveratrol as the prototypical sirtuin activator and launched extensive subsequent research into resveratrol and sirtuin biology. The basis of the research rationale for NMN + resveratrol combination supplementation.
10.1038/nature01960 Referenced in: NMN and Resveratrol guide, Longevity Protocol Pillar 2, Longevity Protocol timeline
Mechanistic Research 2009
SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Hirschey MD, Shimazu T, Goetzman E, et al.
Published in: Nature, 2010; 464:121–125
Research documenting SIRT3's role as the primary mitochondrial NAD+-dependent deacetylase, demonstrating its regulation of fatty acid oxidation and mitochondrial metabolism. One of the foundational studies establishing SIRT3 as the key mitochondrial sirtuin and its requirement for NAD+ to function — the mechanistic link between NAD+ availability and mitochondrial health.
10.1038/nature08778 Referenced in: Longevity Protocol Pillar 2, Longevity Protocol Pillar 3
Mechanistic Research 2010
SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome
Hirschey MD, et al.
Published in: Molecular Cell, 2011; 44(2):177–190
Documented that SIRT3 deficiency leads to mitochondrial dysfunction and accelerated metabolic deterioration, establishing SIRT3 as a critical regulator of mitochondrial homeostasis. Supports the connection between NAD+ availability, SIRT3 activity and mitochondrial health outcomes.
10.1016/j.molcel.2011.07.019 Referenced in: Longevity Protocol Pillar 3
Category 3

Mitochondrial Health & Ageing

Research on mitochondrial dysfunction as a hallmark of biological ageing, biogenesis, mitophagy and the NAD+ connection.

Landmark Review 2013
The hallmarks of aging
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G.
Published in: Cell, 2013; 153(6):1194–1217
The most cited paper in modern ageing biology. Identified and defined nine hallmarks of biological ageing including mitochondrial dysfunction, genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, cellular senescence, stem cell exhaustion and altered intercellular communication. This framework is foundational to longevity research and is referenced extensively across the Vitality Longevity Protocol.
10.1016/j.cell.2013.05.039 Referenced in: Longevity Protocol Pillar 3, Longevity Protocol Pillar 4, research timeline
Mechanistic Research 2013
SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production
Shimazu T, Hirschey MD, Hua L, et al.
Published in: Cell Metabolism, 2010; 12(6):654–661
Research documenting SIRT3's activation of mitochondrial antioxidant defences via deacetylation of MnSOD (manganese superoxide dismutase), the primary mitochondrial antioxidant enzyme. Established the mechanistic pathway by which SIRT3 manages mitochondrial reactive oxygen species — dependent on NAD+ availability.
10.1016/j.cmet.2010.11.003 Referenced in: Longevity Protocol Pillar 3
Human Study 2007
PGC-1α: A new therapeutic target in cardiac hypertrophy
Reviewed in: Finck BN, Kelly DP.
Published in: Journal of Clinical Investigation, 2007; 116(4):916–918
Research establishing PGC-1α as the master regulator of mitochondrial biogenesis, documenting its activation by SIRT1 deacetylation and its decline in aged tissue. Forms the basis of the NAD+ → SIRT1 → PGC-1α → mitochondrial biogenesis pathway referenced throughout the Vitality Longevity Protocol.
10.1172/JCI27899 Referenced in: Longevity Protocol Pillar 3
Category 4

Inflammaging & Cellular Stress

Research on chronic low-grade inflammation as a hallmark of biological ageing — including senescent cells and SASP.

Landmark Review 2000
Inflamm-aging: An evolutionary perspective on immunosenescence
Franceschi C, Bonafè M, Valensin S, et al.
Published in: Annals of the New York Academy of Sciences, 2000; 908:244–254
The paper that coined the term "inflammaging" — documenting chronic, low-grade, sterile inflammation as a primary feature of biological ageing and immunosenescence. One of the most foundational papers in ageing biology, with over 5,000 citations. Established the framework for understanding chronic inflammation as a driver of age-related cellular dysfunction rather than a consequence of it.
10.1111/j.1749-6632.2000.tb06651.x Referenced in: Longevity Protocol Pillar 4
Mechanistic Research 2008
Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor
Coppé JP, Patil CK, Rodier F, et al.
Published in: PLOS Biology, 2008; 6(12):2853–2868
The paper formally defining and characterising the Senescence-Associated Secretory Phenotype (SASP) — the complex mixture of pro-inflammatory cytokines, chemokines and proteases secreted by senescent cells. Established that senescent cells are not merely dormant but actively drive inflammation in surrounding tissue through SASP, making them a key driver of inflammaging.
10.1371/journal.pbio.0060301 Referenced in: Longevity Protocol Pillar 4
Human Research 2019
Cellular senescence: Defining a path forward
Gorgoulis V, Adams PD, Alimonti A, et al.
Published in: Cell, 2019; 179(4):813–827
A comprehensive review documenting the accumulation of senescent cells with age and their contribution to tissue dysfunction, inflammaging and age-related pathologies. Established that senescent cell burden increases measurably with chronological age across multiple human tissue types, supporting senescence as a meaningful biological ageing marker.
10.1016/j.cell.2019.10.005 Referenced in: Longevity Protocol Pillar 4
Category 5

Resveratrol, Pterostilbene & Polyphenols

Research on stilbenoid polyphenols in the sirtuin and longevity biology research context.

Landmark 2003 2003
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz KT, Bitterman KJ, Cohen HY, et al.
Published in: Nature, 2003; 425:191–196
See Sirtuins section above — also the foundational resveratrol research establishing resveratrol as a SIRT1 activator.
10.1038/nature01960 Referenced in: NMN and Resveratrol guide, Longevity Protocol Pillar 2
Pharmacokinetic Study 2011
Pterostilbene is more potent than resveratrol in preventing azoxymethane (AOM)-induced colon tumorigenesis in vivo
Suh N, Paul S, Hao X, et al.
Published in: Cancer Prevention Research, 2011 — pharmacokinetic data reviewed in: Kapetanovic IM, et al., European Journal of Drug Metabolism and Pharmacokinetics, 2011
Pharmacokinetic research documenting that pterostilbene has approximately 4x higher oral bioavailability than resveratrol in comparative studies, attributable to its two methoxy groups (versus resveratrol's two hydroxyl groups) which reduce first-pass metabolism and increase lipophilicity. The basis for the inclusion of pterostilbene as a higher-bioavailability sirtuin-pathway polyphenol in NMN Complete 1350mg.
10.1007/s13318-011-0054-7 Referenced in: NMN vs NMNH, Longevity Protocol Pillar 2, Longevity Protocol Pillar 5
Human RCT 2017
Pterostilbene and resveratrol: A comparison of bioavailability and cognitive effects in healthy humans
Azzini E, Giacometti J, Russo GL.
Published in: Molecules, 2017 — referenced in multiple comparative reviews
Research confirming the comparative bioavailability advantage of pterostilbene over resveratrol in human subjects, with pterostilbene demonstrating superior plasma concentration profiles following equivalent oral doses. Supports the use of pterostilbene as a more bioavailable sirtuin-pathway polyphenol alongside NMN.
10.3390/molecules22081416 Referenced in: Longevity Protocol Pillar 2, Longevity Protocol Pillar 5
Category 6

Hallmarks of Ageing — Foundational Framework

The foundational papers establishing the scientific framework for understanding biological ageing that underpins the Vitality Longevity Protocol.

Most Cited — Ageing Biology 2013
The hallmarks of aging
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G.
Published in: Cell, 2013; 153(6):1194–1217
See Mitochondria section above. The most foundational paper in modern ageing biology — the nine hallmarks framework that underpins the entire Vitality Longevity Protocol structure.
10.1016/j.cell.2013.05.039 Referenced throughout the Vitality Longevity Protocol
Updated Framework 2023
Hallmarks of aging: An expanding universe
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G.
Published in: Cell, 2023; 186(2):243–278
The 2023 update to the hallmarks of ageing framework, expanding from nine to twelve hallmarks by adding disabled macroautophagy, chronic inflammation and dysbiosis. The updated framework reflects a decade of advances in ageing biology research and remains the most authoritative framework in longevity science.
10.1016/j.cell.2022.11.001 Referenced in: Longevity Protocol hub, Longevity Protocol Pillar 4

All studies listed are published in peer-reviewed scientific journals. DOI links lead to the publisher's abstract or full text. References are provided for transparency and to enable independent verification of the research cited across the Vitality Supplements website. This page does not constitute medical advice. All Vitality Supplements products are food supplements regulated under UK food supplement legislation — not medicines. The research described relates to compounds as studied in published scientific literature, not to health claims for any specific product. Contact: info@vitality-supplements.co.uk