This review examines eleven longevity molecules, from ubiquinol to resveratrol, and for each one, it reports what has been observed and under what conditions.
Before each profile, there is a distinction that changes how the results should be interpreted: the distinction between lifespan and healthy lifespan.
At NUTRALAB, we work with raw materials and formulations every day. For some of these molecules, there are studies conducted in humans, while for others, there is only research on cells and in animal models. We indicate the level of evidence achieved for each profile, from solid clinical evidence to that which is still preliminary.
Lifespan and healthspan: lifespan and years in good health
Modern research has placed the distinction between lifespan and healthspan at the centre of the debate.
Lifespan is the length of life. Healthspan is the length of life in good health — the years lived with full physical and cognitive function, without chronic disabilities or dependence on therapies.
The goal of the most advanced research is, above all, to extend healthspan. This means delaying the onset of age-related diseases and maintaining energy, mental clarity and independence for as long as possible.
In this context, nutraceuticals take on a specific and, in some cases, scientifically substantiated role.
The biological mechanisms of ageing: where nutraceuticals act
Cells age along certain well-described pathways. It is on these that the nutraceuticals studied for longevity act.
Oxidative stress and mitochondrial decline. Mitochondria, the cell's powerhouses, lose efficiency with age and produce increasing amounts of free radicals. Damage accumulates in DNA, proteins and cell membranes.
Chronic silent inflammation (inflammaging). The Italian gerontologist Claudio Franceschi coined this term for a silent, low-grade systemic inflammatory state that accompanies ageing. It increases the risk of cardiovascular disease, neurodegeneration and diabetes.[1]
Decline of NAD+. Nicotinamide adenine dinucleotide is an essential coenzyme for energy metabolism, DNA repair and the regulation of sirtuins — proteins associated with longevity. Its levels decrease significantly with age.[2]
Cellular senescence. Senescent cells stop dividing but do not die: they release inflammatory signals that damage surrounding tissues. Their progressive accumulation is considered one of the main drivers of organ ageing.[3]
Reduced autophagy. Autophagy is the process by which cells eliminate damaged components and renew themselves. Its reduction with age contributes to the accumulation of cellular debris associated with neurodegeneration and inflammation. The discovery of its molecular mechanism earned Yoshinori Ohsumi the 2016 Nobel Prize in Medicine.
Supplements and longevity: the most studied molecules in humans
The level of evidence distinguishes between three tiers: studies on cells and animals, observational studies, and controlled clinical trials in humans. Only the latter provide robust evidence of efficacy.
NAD+ and its precursors: NMN and NR
Level of evidence: ★★★★☆ — Solid on biomarkers, promising on clinical outcomes
NAD+ is probably the most studied molecule in the field of longevity in the last ten years. Since NAD+ taken directly does not easily cross cell membranes, research has focused on its precursors: nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR).
A randomised, double-blind clinical trial has shown that 250 mg/day of NMN for 12 weeks significantly increases blood NAD+ levels and improves gait speed and muscle function in healthy older men.[4]
A 2024 meta-analysis that aggregated data from 12 clinical trials on 513 participants confirmed significant effects on glycaemia, the lipid profile and an increase in circulating NAD+.[5]
Ubiquinol (Coenzyme Q10 active form)
Level of evidence: ★★★★★ — Solid, with clinical trials on relevant outcomes
Coenzyme Q10 is present in every cell and is essential for the mitochondrial production of ATP. Its levels decline with age, and statin therapies accelerate this decline.
Ubiquinol is the biologically active and already reduced form of CoQ10, the predominant one in healthy blood (over 90% of plasma CoQ10). It does not require metabolic conversion and is directly available to the cells.
An epidemiological study conducted on over 1,300 individuals has shown that a higher proportion of ubiquinone to ubiquinol in the blood is an independent predictor of all-cause mortality.[6]
A study-by-study comparison of the two forms can be found in the article Ubiquinol or ubiquinone: which coenzyme Q10 to choose.
Organic astaxanthin
Level of evidence: ★★★★☆ — Very solid on antioxidation and mitochondrial metabolism
Astaxanthin is a carotenoid produced by the alga Haematococcus pluvialis, the only source approved for human use. It has one of the highest antioxidant powers in its class. It crosses both the blood-brain barrier and the inner mitochondrial membrane, thus protecting two of the biological systems most vulnerable to ageing.
A comprehensive review has documented the benefits of astaxanthin against age-related diseases in multiple organs, including its interaction with longevity-associated proteins: Nrf2, FOXO3, Sirt1 and Klotho.[7]
Resveratrol
Level of evidence: ★★☆☆☆ — Fascinating mechanisms, but disappointing clinical evidence
Resveratrol is a polyphenol found in red grapes, red wine and some medicinal plants. The discovery of its ability to activate SIRT1 — one of the sirtuins associated with longevity — generated enormous scientific attention between 2003 and 2010.
The clinical reality has been more complex. A systematic review and dose-response meta-analysis of RCTs has analysed the entire body of available clinical trials. Despite more than 150 studies, there is still no conclusive clinical evidence sufficient to recommend resveratrol in a specific healthcare context.[8]
The main problem is bioavailability. After oral intake, resveratrol is rapidly metabolised in the intestine and liver, and plasma concentrations remain much lower than those required to produce the effects observed in preclinical models.
Spermidine
Level of evidence: ★★★☆☆ — Promising, robust epidemiological data, clinical trials in progress
Spermidine is a natural polyamine present in all cells of living organisms. In food, it is found in significant concentrations in natto, whole grains, legumes and some varieties of aged cheese.
Its main mechanism of action is the induction of autophagy. An epidemiological study of over 800 individuals followed for 20 years has associated a higher dietary intake of spermidine with a reduction in cardiovascular and all-cause mortality.[9]
Clinical trials with direct supplementation are still limited, but the initial results are encouraging. A study on older adults reported improvements in immune response and a reduction in markers of cellular senescence.
Quercetin and Fisetin (natural senolytics)
Level of evidence: ★★★☆☆ — Strong preclinical data, human clinical trials still limited
Quercetin and fisetin are two plant flavonoids studied for their potential senolytic activity, i.e. the ability to selectively eliminate senescent cells. These are the so-called "zombie cells", which contribute to age-related chronic inflammation.
The preclinical data from cell and animal models are convincing. In a preliminary trial by the Mayo Clinic on patients with diabetic kidney disease, the experimental protocol of dasatinib plus quercetin significantly reduced senescent cells in tissues and senescence markers in plasma.[10]
The main limitation, which it shares with many polyphenols, is its variable bioavailability. Phytosomal forms and modified-release formulations are attempting to overcome this obstacle.
Berberine
Level of evidence: ★★★★☆ — Solid for glycaemic and lipid metabolism, emerging data on longevity
Berberine is an alkaloid of plant origin found in Berberis vulgaris. Its main mechanism of action is the activation of AMPK, the same metabolic pathway that is activated by physical exercise.
A review has documented the molecular mechanisms of berberine, including its ability to regulate AMPK/mTOR and sirtuins. The same review described the effects on glycaemia and lipid profile observed in clinical studies.[11]
Note: berberine can interact with several medicines and its use requires caution in individuals undergoing drug therapy.
Nattokinase
Level of evidence: ★★★★☆ — Solid for cardiovascular health and circulation
Nattokinase is a fibrinolytic enzyme extracted from natto, a traditional Japanese fermented food. The line of research concerning it is that of cardiovascular risk factors. Cardiovascular diseases remain the leading cause of premature death in Western countries.
A meta-analysis of randomised clinical trials has documented the significant effects of nattokinase on cardiovascular risk factors, including blood pressure, lipid profile and coagulation markers.[12]
Individual randomised human trials have observed measurable and limited effects. After a single oral dose of 2,000 FU, fibrinolysis and anticoagulation markers increase in the following hours, while remaining within normal values.[18] In two 8-week, double-blind trials on subjects with high-normal blood pressure, systolic and diastolic blood pressure and von Willebrand factor, a cardiovascular risk marker, were reduced.[19][20]
A review has further investigated the lipid-lowering mechanisms of nattokinase and described its fibrinolytic activity.[13]
Vitamin D and vitamin K2
Level of evidence: ★★★★★ — Among the nutraceuticals with the most solid scientific support
Vitamin D is actually a hormone. It influences the expression of over 1,000 genes, the immune system, bone health, muscle tone and the inflammatory response. Its deficiency is endemic in the adult Italian population.
In a meta-analysis, higher serum levels of vitamin D were associated with greater telomere length, one of the most reliable markers of biological ageing.[14] Research is also studying its combination with vitamin K2 in the MK-7 form for the role of vitamin K in normal calcium metabolism.
Omega-3 (EPA and DHA)
Level of evidence: ★★★★★ — Among the nutraceuticals with the most extensive body of research
Long-chain omega-3 fatty acids have accumulated decades of clinical research on inflammation, cardiovascular health, cognitive function and longevity. The benefits for inflammatory and lipid parameters are well documented.
In a meta-analysis of randomised clinical trials, participants who regularly supplemented with EPA and DHA had a lower incidence of cardiovascular events.[15]
Curcumin
Level of evidence: ★★★☆☆ — Excellent mechanisms, bioavailability the real problem
Curcumin is the main active polyphenol in turmeric. It acts on multiple molecular targets linked to ageing: it inhibits NF-κB (inflammation), activates Nrf2 (antioxidant defence), and modulates mTOR (senescence). In preclinical models, it also shows senolytic activity.
A meta-analysis of RCTs has confirmed significant effects of curcumin on inflammatory markers (CRP, IL-6) and on oxidative stress in subjects with metabolic syndrome.[16]
Its main limitation is its extremely low oral bioavailability: standard curcumin is almost completely metabolised before reaching systemic circulation. Enhanced absorption formulations — with turmeric essential oils like BCM-95®/Curcugreen® or phytosomal ones — significantly improve its absorption.
A comparison of longevity nutraceuticals: the evidence table
| Molecule | Human evidence | Critical point |
|---|---|---|
| Ubiquinol (CoQ10) | ★★★★★ | Form: ubiquinol vs ubiquinone |
| Omega-3 EPA/DHA | ★★★★★ | Quality and dosage |
| Vitamin D + K2 | ★★★★★ | Very widespread deficiency |
| NMN / NR | ★★★★☆ | Robust biomarkers, clinical outcomes in development |
| Organic astaxanthin | ★★★★☆ | Certified H. pluvialis source |
| Berberine | ★★★★☆ | Caution with drug interactions |
| Nattokinase | ★★★★☆ | Enzymatic activity verified per batch |
| Spermidine | ★★★☆☆ | Clinical trials still limited |
| Quercetin / Fisetin | ★★★☆☆ | Variable bioavailability |
| Curcumin | ★★★☆☆ | Advanced formulation essential |
| Resveratrol | ★★☆☆☆ | Clinical evidence still insufficient |
The longevity market: how to recognise what doesn’t work
The global longevity market is estimated to be worth over 19 billion dollars in 2025, with projections of 58 billion by 2035. This growth brings with it a serious problem: the proliferation of products that use the term "longevity" as a marketing lever without real scientific support.
Some warning signs to recognise:
"Window-dressing doses": dozens of longevity ingredients present in doses too low to produce a documented biological effect, put there just to be able to write the name of each molecule on the label.
Confusion between preclinical and clinical studies: almost everything works in cell models and in animals. What matters for humans are controlled clinical trials, which are much rarer and often produce more modest results.
Overestimation of bioavailability: a potentially effective molecule becomes useless if it is not absorbed. Many supplements use the least bioavailable forms for cost reasons.
Biological age marketing: tests used as a sales lever without robust clinical validation of the tool.
Nutraceuticals and lifestyle: the role of context
The context in which a nutraceutical is taken largely determines if and how much the molecule can express its biological potential. Diet, physical activity, sleep quality and stress management all matter.
A study by Prof. Valter Longo of the University of Southern California examined the fasting-mimicking diet, a cyclical, low-calorie dietary protocol. The study showed significant reductions in markers of biological ageing, including estimated biological age, cardiovascular risk factors and inflammatory markers.[17]
The most effective nutraceuticals amplify the benefits of an already healthy lifestyle, without replacing it.
This article has been written by the NUTRALAB scientific team for informational and educational purposes. It does not replace the advice of a doctor or a healthcare professional. Before starting any supplementation, particularly in the presence of medical conditions, pregnancy, or ongoing drug therapies, it is recommended to consult your doctor.
Frequently asked questions
Which supplements are most studied for longevity?
The most studied supplements in relation to ageing, metabolism and cellular health include omega-3, vitamin D, coenzyme Q10, NAD+ precursors, astaxanthin, curcumin and some plant molecules such as berberine, quercetin and fisetin. However, the level of evidence varies greatly from substance to substance.
Can supplements extend life?
To date, there are no supplements that can guarantee an increase in human lifespan. Research focuses mainly on biomarkers, metabolic health, inflammation, mitochondrial function and the quality of ageing.
What is the difference between lifespan and healthspan?
Lifespan indicates the total duration of life, while healthspan indicates the years lived in good health, with good physical and cognitive function. In modern longevity research, the main goal is often to improve healthspan rather than simply increasing the number of years lived.
What is the main limitation of longevity supplements?
One of the main limitations is the difference between promising results observed in cell or animal studies and solid clinical evidence in humans. Bioavailability, dosage, raw material quality and the duration of studies are also decisive aspects.
Can nutraceuticals replace diet and lifestyle?
No. Nutraceuticals can play a supportive role in some contexts, but they are no substitute for a balanced diet, regular physical activity, adequate sleep and stress management.
How to choose a longevity supplement?
It is useful to evaluate the level of evidence in humans, dosage, ingredient form, bioavailability, raw material quality, label transparency and the consistency of the formulation. It is important to be wary of products that promise rapid or guaranteed anti-ageing effects.
Further reading
- What nutraceuticals are and why they work
- How to choose a quality supplement
- Supplements in the morning or evening, on a full or empty stomach: a practical guide
Scientific sources
- Franceschi C, et al. (2000). Inflamm-aging. An evolutionary perspective on immunosenescence. Annals of the New York Academy of Sciences, 908, 244–254. PubMed
- Yoshino M, et al. (2018). Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metabolism, 27(2), 513–528. PubMed
- Di Micco R, et al. (2021). Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nature Reviews Molecular Cell Biology, 22(2), 75–95. PubMed
- Igarashi M, et al. (2022). Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. npj Aging, 8, 5. PubMed
- Zhang J, et al. (2024). Efficacy of oral nicotinamide mononucleotide supplementation on glucose and lipid metabolism for adults: a systematic review with meta-analysis on randomized controlled trials. Critical Reviews in Food Science and Nutrition, 65(22), 4382–4400. PubMed
- Haneke D, et al. (2026). Higher Redox State of Coenzyme Q10 Is Associated with Higher Risk of All-Cause Mortality in a Sample from the Northern German General Population. Antioxidants, 15(3), 343. MDPI | PubMed
- Alugoju P, et al. (2023). Health benefits of astaxanthin against age-related diseases of multiple organs: A comprehensive review. Critical Reviews in Food Science and Nutrition, 63(31), 10709–10774. PubMed
- Mansouri F, et al. (2025). Impact of Resveratrol Supplementation on Human Sirtuin 1: A GRADE-Assessed Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials. Journal of the Academy of Nutrition and Dietetics, 125(9), 1299–1314. PubMed
- Kiechl S, et al. (2018). Higher spermidine intake is linked to lower mortality: a prospective population-based study. American Journal of Clinical Nutrition, 108(2), 371–380. PubMed
- Hickson LJ, et al. (2019). Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine, 47, 446–456. PubMed
- Sun A, et al. (2024). Molecular mechanisms, targets and clinical potential of berberine in regulating metabolism: a review focussing on databases and molecular docking studies. Frontiers in Pharmacology, 15, 1368950. PubMed
- Dong S, et al. (2024). Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PubMed
- Wei C, et al. (2025). Research Progress of Nattokinase in Reducing Blood Lipid. Nutrients, 17(11), 1784. MDPI
- Tabar MS, et al. (2025). The association of serum levels of vitamin D with leucocyte telomere length, as a marker of biological aging: A meta-analysis. PubMed
- Dong S, et al. (2024). The effect of omega-3 Polyunsaturated Fatty Acid (PUFA) prescription preparations on the prevention of clinical cardiovascular disease: a meta-analysis of RCTs. Nutrition Journal, 23(1), 157. PubMed
- Qiu L, et al. (2023). Effects of dietary polyphenol curcumin supplementation on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials. Frontiers in Endocrinology, 14, 1216708. PubMed
- Brandhorst S, Levine ME, Wei M, et al. (2024). Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nature Communications, 15(1), 1309. Nature | PubMed
- Kurosawa Y, et al. (2015). A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Scientific Reports, 5, 11601. DOI | PubMed
- Kim JY, et al. (2008). Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertension Research, 31(8), 1583–1588. DOI | PubMed
- Jensen GS, et al. (2016). Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial. Integrated Blood Pressure Control, 9, 95–104. DOI | PubMed
Category
Science and researchTopics
- anti-ageing
- astaxanthin
- berberine
- healthspan
- longevity
- NAD+
- nattokinase
- NMN
- nutraceuticals
- omega-3
- quercetin
- resveratrol
- spermidine
- ubiquinol
By the NUTRALAB Editorial Team
Scientific review: Giuliano D'Alterio, Pharmaceutical chemist — 11 August 2026
