The Science of Longevity Supplements: What the Evidence Actually Supports

From NAD+ boosters to GLP-1 medications, longevity science is moving fast. Here's a science-based look at what the human research shows — and how to tell a proven ingredient from a promising one.

NMN, resveratrol, rapamycin, the new generation of GLP-1 medications…supplements and drugs once confined to niche biohacking communities and research labs are now the subject of wellness headlines, dinner-table debates, and a fast-expanding market built on a single promise: more healthy years.

Behind that promise sits a real and rapidly evolving body of science, but the strength of the evidence varies between compounds. Some longevity ingredients are backed by large human trials measuring outcomes that lend to longevity, such as heart attacks, cognition, and survival rates. Others rest on studies in mice, or lab studies based on a shift in a single marker.

It's important to note that longevity is genuinely hard to measure in a human trial. Aging unfolds over decades, so a study designed to prove that an intervention helps people live longer would need to follow thousands of participants for many years—a slow, expensive, and rarely-funded process. To work around this, researchers track shorter-term signals such as inflammatory markers, or a "biological age" estimated from molecular clocks. Though many trials are short, modest in size, and run in a specific group of people, moving one of those markers is an encouraging early signal.

In this article, we look at the most popular longevity supplements and medications through the lens of published, peer-reviewed research.

Over-the-Counter Supplements

NAD+ boosters (NMN and NR)

NAD+ is having a moment, and the rationale is appealing. It is a coenzyme every cell uses for energy and repair, its levels fall with age in some tissues including the brain, muscle, and fat. Supplements such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are precursors designed to restore NAD levels.^1,2 A 2026 systematic review of 113 studies, including 33 in humans, found that oral NR and NMN reliably raise NAD+ levels and are well tolerated over weeks to months.¹

The question is whether higher NAD+ translates into better health, and here the evidence is far less settled.

Recent peer-reviewed meta-analyses give a grounded sense of where that question currently stands. Pooling eight randomized trials in 342 mostly non-diabetic middle-aged and older adults (NMN at 250–2,000 mg/day for 2–12 weeks), oral NMN showed no significant benefit on fasting glucose, insulin, HbA1c, insulin resistance, or blood lipids.⁵¹ A separate meta-analysis of NMN and NR trials in adults over 60 likewise found no significant improvement in muscle mass, handgrip strength, or walking speed.⁵²

That said, there is a clear positive human result that has been proven: a 10-week trial published in Science found that NMN improved muscle insulin sensitivity—but in postmenopausal women with prediabetes who were overweight or obese, an at-risk group rather than the general population.⁵³ The most striking disease-modifying effects otherwise remain largely in rodent studies, with long-term human outcomes still being established.²

Two nuances are worth holding in mind as the field matures. Dose to benefit does not have a linear correlation—in mice on a mildly obesogenic diet, a high dose of NR actually induced glucose intolerance and fat-tissue dysfunction,⁵⁴ and because NAD+ sits at the center of so many cellular processes, including some relevant to cancer biology, researchers are still mapping the long-term safety of sustained, high-dose use.⁵⁵ NAD+ boosters are a genuinely exciting, fast-moving area whose human benefit story is still being proven, but consumers should remain cautious of high doses.

Resveratrol

Known as the "red-wine molecule," resveratrol has one of the longest research track records in the longevity space. A 2024 systematic review that gathered nearly 200 clinical trials spanning two decades and at least 24 conditions concluded it does consistently lower certain inflammatory markers, which can be promising for longevity since most age-related diseases are correlated with systemic inflammation.³ It is generally well tolerated at up to about a gram a day.³ Where the science gets more complicated is delivery. Resveratrol is rapidly broken down in the gut and liver, meaning very little intact compound reaches circulation at the concentrations that drove excitement in early lab studies. This helps explain why the human trial results, while directionally positive on inflammation, have tended to be more modest than the preclinical story suggested. It's not that the biology is wrong—it's that getting the molecule where it needs to go is genuinely hard.^56,57

Coenzyme Q10 (alone or with selenium)

CoQ10 is one of the less fashionable names on this list, yet it carries some of the strongest and most diverse human outcome data of any supplement here. It powers cellular energy production and acts as an antioxidant, and because the body makes less of it with age, it is a genuine, correctable age-related deficiency rather than a speculative longevity bet.^5,6 There is a clear biological logic to where it helps most: the tissues and processes that depend most heavily on mitochondrial energy are exactly the ones where its decline matters—and that logic shows up repeatedly in the human data.

Cardiovascular health is the best-known example. In the Q-SYMBIO trial, patients with moderate-to-severe heart failure who took CoQ10 had roughly half the rate of major cardiac events over two years (15% versus 26%), alongside lower cardiovascular and all-cause mortality.⁵ In the Swedish KiSel-10 trial, older adults given selenium plus CoQ10 for four years had reduced cardiovascular mortality that was still evident a decade later.⁶ These are hard clinical outcomes—cardiac events and deaths, not just biomarkers—which is relatively rare in the supplement literature; a 2022 review likewise highlighted these heart-failure benefits,³⁵ and a broader 2018 review of reviews agreed CoQ10 may be a useful tool even as it called for larger, more uniform trials.³⁶

The same energy logic extends to fertility, where egg maturation is one of the most energy-intensive processes in the body. A 2024 systematic review and meta-analysis in Annals of Medicine pooled six randomized trials covering 1,529 women with diminished ovarian reserve undergoing IVF or ICSI, and found that CoQ10 pretreatment was associated with a significantly higher clinical pregnancy rate, more oocytes retrieved, and more high-quality embryos, alongside a lower miscarriage rate.⁴⁵ The same pattern appears in men: a 2025 systematic review and meta-analysis of nine randomized trials in 781 men with idiopathic infertility found that CoQ10 significantly improved sperm concentration and motility and raised clinical pregnancy odds, with the clearest gains when it was taken for more than three months.⁴⁶

While the human data is robust and exciting, much of the evidence comes from specific groups—people with heart failure, low selenium status, or diminished ovarian reserve—so CoQ10 is best understood as a targeted, well-tolerated, inexpensive intervention for specific populations and outcomes. Among the supplements reviewed here, the breadth of human evidence makes it stand out.^5,6,36,45,46

Omega-3 fatty acids (EPA and DHA)

Few supplements have been studied as thoroughly as omega-3s, and the picture built up over decades is genuinely encouraging—especially for anyone looking to invest in long-term health on several fronts at once. EPA and DHA are essential fats the body cannot make on its own, and they work through several mechanisms at the same time—calming the chronic, low-grade inflammation ("inflammaging") that underlies much of age-related decline, supporting cardiovascular function, and contributing to both brain and muscle health.^7,8

The cardiovascular evidence is among the strongest of any supplement. A 2021 systematic review and meta-analysis found that omega-3s, and EPA in particular, meaningfully reduced cardiovascular mortality and improved cardiovascular outcomes.^7,8 The effect is clearest at higher doses and in people with existing cardiovascular risk—which is exactly why the large VITAL trial, using just 1 g/day, found no significant effect.⁹ With omega-3s, dose and formulation are key: the EPA-heavy, higher-dose preparations are where the strongest signals appear.^7,8,9

The case is also widening well beyond the heart. The brain is roughly 60% fat, with DHA a key structural component, and a 2025 dose-response meta-analysis of 58 randomized trials found that each additional 2,000 mg/day of omega-3 was associated with measurable gains in attention, perceptual speed, and global cognition — a modest but encouraging signal in adults.⁴⁸ Muscle is the benefit fewer people know about: a 2024 review concluded there is growing evidence that EPA and DHA can help preserve, and perhaps even enhance, muscle strength—directly relevant to staying strong and independent with age—while noting that larger trials are still needed to confirm the effect.⁵⁰ Together, the data shows broad, well-tolerated support for utilizing omega-3 supplementation in healthy aging.

One practical note: because EPA and DHA are highly unsaturated, fish oil can oxidize (go rancid) with heat, light, and air, which can reduce its benefit—so freshness and product quality matter, not just dose.

Vitamin D

Vitamin D is one of the most fundamental nutrients for aging well. The body makes it from sun exposure, and deficiency is remarkably common, particularly in older adults, people with darker skin, those at higher latitudes, and anyone who spends most of their time indoors.

A 2022 meta-analysis found that daily vitamin D supplementation was associated with significantly lower cancer mortality, whereas infrequent large "bolus" doses were not—an indication that steady, consistent intake is what matters.⁴⁷ Therefore, the data supports consistent daily intake as a sensible, low-risk choice to support longevity.^9,47

There is also an intriguing thread tying vitamin D to cellular aging itself. A 2025 meta-analysis of 21 studies and more than 185,000 participants found that higher vitamin D levels were associated with longer leukocyte telomeres—the protective caps on chromosomes whose shortening is a recognized hallmark of aging—an association strongest in people who were deficient.⁴⁹ This correlational evidence is the kind of signal fuelling fresh interest in it for healthy aging.⁴⁹

A daily multivitamin

The humble multivitamin is well-supported for cognitive function. In the COSMOS-Web randomized trial, 3,562 older adults took either a daily multivitamin or a placebo, and the multivitamin group performed significantly better on memory at one year, the trial's prespecified primary outcome.¹⁰ The effect is modest, but it comes from a large, well-conducted randomized trial, which is more than most premium longevity products can claim, and at a fraction of the cost.

For the broader goals of preventing cardiovascular disease or cancer, the US Preventive Services Task Force concluded in 2022 that the evidence is insufficient to assess whether multivitamins help, and specifically recommended against beta-carotene and vitamin E supplements for that purpose.³⁷ The accompanying commentary emphasized that the most reliable strategy remains an evidence-based one: a balanced diet high in fruits and vegetables, plus physical activity.³⁷ A multivitamin is inexpensive and low-risk, but it is not a substitute for those fundamentals.

Creatine

Creatine has steadily earned a place beyond the gym. It fuels rapid bursts of cellular energy in muscle and brain, and reviews of clinical data show that, particularly when combined with resistance training, it improves muscle strength, lean body mass, and physical function in older adults.¹¹ Its effects on cognition are more tentative; a 2025 systematic review found modest, mixed results, strongest in people who began with lower creatine levels.¹² The practical takeaway is that it works best alongside exercise rather than in place of it, and preserving muscle is itself one of the more reliable contributors to healthy aging.^11,12

Urolithin A

Urolithin A is a compound the gut microbiome produces from foods such as pomegranate, and it activates mitophagy, the cell's recycling of worn-out mitochondria.^13,14 It is now among the better-studied longevity supplements in humans, with several randomized trials. The first-in-human study, in healthy sedentary elderly adults, established a favourable safety profile and showed that four weeks of supplementation (500–1,000 mg/day) shifted mitochondrial gene expression in muscle and improved plasma biomarkers—a molecular signature of better mitochondrial health, but without any functional outcome.³⁸ Later trials looked for functional gains: improved muscle endurance and lower inflammatory and mitochondrial biomarkers in adults aged 65 to 90,¹³ and gains in muscle strength in middle-aged adults.¹⁴ A 2025 trial extended the work to immune aging, where urolithin A met its primary outcomes—expanding naive-like, less-exhausted CD8+ T cells and increasing their metabolic capacity in middle-aged adults over four weeks.⁴⁰

However the trials measuring everyday physical function have repeatedly fallen short of their headline goals. In the older-adult study, the two pre-specified primary outcomes—six-minute walk distance and maximal ATP production in the hand muscle—showed no significant improvement over placebo; the benefits appeared only in secondary measures such as muscle endurance and blood biomarkers.¹³ In the middle-aged study, the pre-specified primary endpoint (peak power output) likewise showed no significant change versus placebo.¹⁴ And an eight-week trial in 20 resistance-trained male athletes found significant gains in muscle-endurance measures but no significant change in maximal strength (one-rep-max bench press and squat).³⁹ The consistent thread is reassuring safety and reliable effects on mitochondrial, inflammatory, and immune biomarkers, set against inconsistent results on the functional outcomes that matter most.^{13,14,38,39,40} The early signals are genuinely interesting, but the muscle-function studies have not delivered a clear win on the outcomes they set out to measure, and the authors themselves call for further work to confirm the findings.¹³

Spermidine

Spermidine, a dietary polyamine, is frequently discussed for its proposed role in autophagy and cognitive health, supported largely by animal studies and preliminary human signals.^15,34 The SmartAge trial, a 12-month randomized, double-masked, placebo-controlled study of 100 older adults with subjective cognitive decline, found that spermidine supplementation did not modify memory or biomarkers compared with placebo, with no significant effect on its primary memory outcome.³⁴ The supplement was very well tolerated, and the authors noted exploratory hints on verbal memory and inflammation that would need to be confirmed in future trials at higher doses.³⁴ As it stands, the strongest human trial did not show the hoped-for cognitive benefit.

Alpha-ketoglutarate (AKG)

Alpha-ketoglutarate, marketed in formulations such as Rejuvant, is often promoted with a striking figure: an average drop of about eight years in biological age. That number comes from a study of 42 people measured on a DNA-methylation age test.¹⁷ The analysis, however, was retrospective and had no placebo group, and the authors themselves note that a controlled trial is needed.¹⁷ That placebo-controlled study (ABLE) is, for now, published only as a protocol.¹⁸ An eight-year shift on a laboratory clock is intriguing, but without a control group its cause is unclear.

Prescription Medications

The next group are prescription drugs. None is approved specifically to slow aging, so longevity-related use is off-label and requires medical supervision. Notably, several of them carry larger and more rigorous human trials than most supplements, largely because they were developed to treat disease and obesity, however this is not the same as proving they slow aging itself.

Metformin

Metformin, the first-line diabetes medication, became a longevity candidate because it delays aging in laboratory organisms and because people taking it for diabetes appeared to fare well.^19,20 The human evidence is nuanced. A 2021 review concluded that, on current data, metformin extends healthspan but not lifespan in humans, with the clearest benefits in those who have type 2 diabetes.¹⁹ A 2019 review added two important caveats—not everyone benefits, and some develop side effects—and noted that the TAME trial, designed to test metformin against aging directly, had not yet been reported.²⁰ It is a proven tool in diabetes; for healthy people pursuing longevity, it remains a hypothesis awaiting its defining trial.

Rapamycin

Rapamycin, an mTOR-inhibiting drug, is among the most reproducible lifespan-extenders in animal research, which is precisely why its human data attracts attention.²¹ The PEARL trial randomized 114 healthy adults to placebo or low-dose weekly rapamycin for 48 weeks. It proved reasonably safe, and although its primary target—visceral fat—did not change, women on the higher dose gained lean muscle mass and reported less pain, while some well-being measures improved at the lower dose.²¹ The authors frame it as a safety and healthspan-metrics study rather than proof of extended human lifespan, with larger dose-ranging trials still to come.²¹

GLP-1 medications (semaglutide and tirzepatide)

The GLP-1 drugs, familiar as semaglutide and tirzepatide, hold some of the strongest outcome data. In the SELECT trial of 17,604 people who were overweight, obese or had cardiovascular disease (but did not have diabetes), semaglutide reduced major cardiovascular events by about 20% (6.5% versus 8.0%) and lowered cardiovascular and all-cause mortality, alongside roughly 9 to 10% weight loss.^22,23 A modeling analysis from the SURMOUNT-5 comparison projected a greater reduction in ten-year cardiovascular risk with tirzepatide, driven by greater weight loss.²⁴ The essential context is that these benefits were measured in people with obesity and cardiovascular disease and are largely attributable to weight loss rather than a demonstrated anti-ageing mechanism, and that rapid weight loss can reduce muscle mass.^22,23,24

Targeting Senescent Cells — Senolytics and Senomorphics

Cellular senescence is one of the most active frontiers in longevity science.

As we age, some cells stop dividing, yet resist dying. These senescent cells—sometimes called "zombie cells"—accumulate in tissues and release inflammatory signals, collectively termed the senescence-associated secretory phenotype, or SASP, that damage healthy neighbouring cells.²⁵ Two distinct strategies have emerged to address them.

Senolytics seek out and eliminate senescent cells. Senomorphics take a different approach, decreasing the harmful SASP signals they release, thereby slowing their accumulation and giving the immune system the chance to clear them away.²⁵ Both fall under the umbrella term senotherapeutics.²⁵

The foundation: evidence from animal studies

The case for targeting these cells began with work in mice. Genetically clearing senescent cells delayed the onset of age-related disorders,²⁶ and in a 2016 study, extended median lifespan across two genetic backgrounds without apparent adverse effects.²⁷ These experiments established that senescent cells are not merely a symptom of aging but a contributing cause.^26,27

From the lab to first human trials

The first senolytic agents were identified in 2015: a combination of dasatinib, a prescription cancer drug, and quercetin, a plant flavonoid, which reduced senescent-cell burden and improved healthspan measures in mice.²⁸ Later research identified the flavonoid fisetin as an even more potent natural senolytic in mice,²⁹ and a 2025 study reported that fisetin improved physical function and reduced muscle senescence in aged mice.³⁰

The human evidence is early but expanding. The first pilots used dasatinib plus quercetin: in 14 patients with idiopathic pulmonary fibrosis, an open-label trial produced significant, clinically meaningful improvements in physical function, including walking distance, gait speed, and chair-stand time, though without a placebo group;³¹ and in patients with diabetic kidney disease, the same combination reduced senescent-cell markers in both fat and skin within 11 days—the first direct evidence that senolytics clear these cells in humans.³² A 2023 open-label phase 1 trial then took dasatinib plus quercetin into early Alzheimer's disease in five patients, showing that dasatinib crosses into the cerebrospinal fluid and that the regimen was safe and feasible, while short-term cognitive and neuroimaging measures were unchanged.⁴¹

Beyond these repurposed oral drugs, a purpose-built senolytic has advanced furthest in the eye. UBX1325 (foselutoclax), which blocks the cell-survival protein BCL-xL, was tested as an intravitreal injection for diabetic macular edema in two trials—the Phase 2 BEHOLD study (65 participants, sham-controlled) and the Phase 2b ASPIRE study (52 participants, compared against the standard drug aflibercept). It was well tolerated and produced lasting improvements in vision, with roughly 53% of treated participants needing no rescue anti-VEGF therapy over 48 weeks versus 22% on sham.⁴² Taken together, these studies show how broad the field has become: senolytics are now being studied in humans across idiopathic pulmonary fibrosis,³¹ diabetic kidney disease,³² Alzheimer's disease,⁴¹ diabetic eye disease,⁴² osteoarthritis,⁴³ and age-related frailty.⁴⁴

Two caveats still temper the enthusiasm. The strongest oral-senolytic data rely on dasatinib, a prescription chemotherapy drug, and much of the fisetin evidence remains in animal models;^29,30,31,32 over-the-counter quercetin and fisetin have not been shown to act as effective senolytics in healthy people in these studies. And many of the human trials are small, open-label, disease-specific, or still in progress—including a dedicated fisetin frailty trial (AFFIRM, still enrolling)⁴⁴ and a completed knee-osteoarthritis trial of the senolytic UBX0101.⁴³

Senomorphics: quieting the signals rather than clearing the cells

Senolytics are only half of the senotherapeutic story. Rather than killing senescent cells, senomorphics aim to suppress the inflammatory SASP they release—neutralising their harmful effect on neighboring tissue while leaving the cells in place.²⁵ This is appealing where removing cells outright can have off-target effects, and it lends itself to local, lower-risk delivery, including topically in the skin, where senescent cells also accumulate with age.²⁵

Where the field stands. Senotherapeutics are among the most compelling ideas in longevity science, grounded in causal animal evidence,^26,27 and the first human trials—senolytics in fibrotic, metabolic, neurological and eye disease.^31,32,41,42 But human data remain early: trials are small, often without placebo controls or in disease-specific populations, and no senotherapeutic has yet been shown to extend healthy lifespan in people. It is a frontier with strong mechanistic backing and genuine momentum, not a settled therapy.

In Summary

Strongest human outcome data. GLP-1 medications lead, with measured reductions in cardiovascular events and mortality, in people with obesity and cardiovascular risk and under medical care.^22,23 CoQ10 stands out with replicated, positive randomized-trial data across several different populations—fewer cardiac events and deaths in heart failure⁵ and selenium-deficient elderly adults,⁶ and improved IVF outcomes in women with diminished ovarian reserve⁴⁵—a breadth of hard human evidence few supplements can match.^35,36,45,46 Omega-3s, ideally EPA and at meaningful doses, meaningfully benefit cardiovascular health, with encouraging emerging data on cognition and muscle.^7,8,48,50 Creatine reliably supports muscle and strength, especially with exercise,¹¹ and a daily multivitamin produced a modest but genuine memory benefit in older adults,¹⁰ even as the evidence for preventing cardiovascular disease or cancer remains insufficient.³⁷ Vitamin D is best used to correct a documented deficiency.⁹

Promising but still emerging. Urolithin A has repeated randomized data showing it is safe and reliably shifts mitochondrial and immune biomarkers, but its muscle-function trials missed their primary endpoints, so it remains early and unclear.^{13,14,38,39,40} Senescence-targeting therapies are supported by strong animal evidence and encouraging first human trials, but the best-tested senolytics use prescription drugs, and the topical senomorphic evidence is specific to skin.^{26,27,28,31,32,33,41,42} Rapamycin and metformin show healthspan-related signals without proof of extended human lifespan, and their defining trials are pending.^19,20,21

Still being established. For some compounds the human story is genuinely still being written. NAD+ boosters reliably raise NAD+, with the question of downstream health benefit now under active study.^1,2 Resveratrol has intriguing biology but, after nearly 200 trials, not yet the clinical evidence to match.^3,4 Human data have so far challenged the idea that taurine deficiency drives aging in people;¹⁶ spermidine's main trial did not move memory or biomarkers, though higher doses are being explored;³⁴ and alpha-ketoglutarate's headline result rests on an uncontrolled biological-age analysis awaiting its placebo-controlled follow-up.^17,18

A useful pattern emerges from all of this: the compounds with the strongest human evidence are the ones aimed at a specific, measurable target—cardiovascular risk, muscle loss, a documented deficiency—while those promoted mainly on animal lifespan or biomarker shifts are earlier in their journey. Encouragingly, most were well tolerated over the periods studied. The goal here isn't to talk anyone out of curiosity about longevity science—it's the opposite: the field is moving quickly and genuinely exciting, and understanding where each compound sits on the evidence curve is what lets you engage with it confidently and spend your attention (and money) where the data are strongest today.

This article is intended for general education and is not medical advice. Individual circumstances vary, and decisions about supplements or prescription medications should be made with a qualified healthcare professional.

Sources

1. Gallagher C, Emmanuel OO. NAD+ supplementation for anti-aging and wellness: a PRISMA-guided systematic review of preclinical and clinical evidence. Ageing Research Reviews, 2026.
2. Song Q, et al. The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update. Advances in Nutrition, 2023.
3. Brown K, et al. Resveratrol for the Management of Human Health: A Systematic Review of Resveratrol Clinical Trials. International Journal of Molecular Sciences, 2024.
4. de Ligt M, et al. No effect of resveratrol supplementation after 6 months on insulin sensitivity in overweight adults: a randomized trial. American Journal of Clinical Nutrition, 2020.
5. Mortensen SA, et al. The Effect of Coenzyme Q10 on Morbidity and Mortality in Chronic Heart Failure (Q-SYMBIO). JACC: Heart Failure, 2014.
6. Alehagen U, Aaseth J, Johansson P. Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years (KiSel-10). PLOS ONE, 2015.
7. Khan SU, et al. Effect of omega-3 fatty acids on cardiovascular outcomes: a systematic review and meta-analysis. EClinicalMedicine, 2021.
8. Zhang W, et al. Unraveling the discrepancies between REDUCE-IT and STRENGTH trials with omega-3 fatty acids. Frontiers in Nutrition, 2024.
9. Manson JE, Bassuk SS, Buring JE. Principal Results of the VITamin D and OmegA-3 TriaL (VITAL) and Updated Meta-analyses. Journal of Steroid Biochemistry and Molecular Biology, 2020.
10. Yeung L-K, et al. Multivitamin Supplementation Improves Memory in Older Adults: A Randomized Clinical Trial (COSMOS-Web). American Journal of Clinical Nutrition, 2023.
11. Li N. Creatine supplementation and exercise in aging: a narrative review of the muscle–brain axis. Frontiers in Nutrition, 2026.
12. Marshall S, et al. Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults. Nutrition Reviews, 2025.
13. Liu S, et al. Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial. JAMA Network Open, 2022.
14. Singh A, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Reports Medicine, 2022.
15. Wirth M, et al. Effects of spermidine supplementation on cognition and biomarkers (SmartAge) — study protocol for a randomized controlled trial. Alzheimer's Research & Therapy, 2019.
16. Marcangeli V, et al. Experimental Evidence Against Taurine Deficiency as a Driver of Aging in Humans. Aging Cell, 2025.
17. Demidenko O, et al. Rejuvant, an alpha-ketoglutarate based formulation, conferred an average 8-year reduction in biological aging (TruAge DNA methylation test). Aging, 2021.
18. Sandalova E, et al. Alpha-ketoglutarate supplementation and Biological Age in middle-aged adults (ABLE) — intervention study protocol. GeroScience, 2023.
19. Mohammed I, et al. A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan. Frontiers in Endocrinology, 2021.
20. Soukas AA, Hao H, Wu L. Metformin as Anti-Aging Therapy: Is It for Everyone? Trends in Endocrinology & Metabolism, 2019.
21. Moel M, et al. Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging, 2025.
22. Deanfield J, et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. The Lancet, 2024.
23. Kotit S, Sous M. SELECT: GLP-1 receptor agonist in obese patients with cardiovascular disease in the absence of diabetes. Global Cardiology Science & Practice, 2024.
24. Mamas MA, et al. Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial. European Heart Journal Open, 2025.
25. Di Micco R, et al. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nature Reviews Molecular Cell Biology, 2021.
26. Baker DJ, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 2011.
27. Baker DJ, et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature, 2016.
28. Zhu Y, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell, 2015.
29. Yousefzadeh MJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 2018.
30. Murray KO, et al. Intermittent Supplementation With Fisetin Improves Physical Function and Decreases Cellular Senescence in Skeletal Muscle With Aging. Aging Cell, 2025.
31. Justice JN, et al. Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study. EBioMedicine, 2019.
32. Hickson LJ, et al. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine, 2019.
33. Zonari A, et al. Clinical efficacy of OS-01 peptide formulation in reducing the signs of periorbital skin aging. International Journal of Cosmetic Science, 2024.
34. Schwarz C, et al. Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial (SmartAge). JAMA Network Open, 2022.
35. Filipiak KJ, Surma S, Romańczyk M, Okopień B. Heart Failure — Do We Need New Drugs or Have Them Already? A Case of Coenzyme Q10. Journal of Cardiovascular Development and Disease, 2022.
36. Jafari M, et al. Coenzyme Q10 in the treatment of heart failure: A systematic review of systematic reviews. Indian Heart Journal, 2018.
37. Jia J, Cameron NA, Linder JA. Multivitamins and Supplements — Benign Prevention or Potentially Harmful Distraction? (Editorial). JAMA, 2022.
38. Andreux PA, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism, 2019.
39. Zhao H, et al. Assessment of Urolithin A effects on muscle endurance, strength, inflammation, oxidative stress, and protein metabolism in male athletes with resistance training: an 8-week randomized, double-blind, placebo-controlled study. Journal of the International Society of Sports Nutrition, 2024.
40. D'Amico D, et al. Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial. Nature Aging, 2025.
41. Gonzales MM, et al. Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial (SToMP-AD). Nature Medicine, 2023.
42. Khanani AM, et al. Safety and Efficacy of Senolytic Candidate UBX1325 for Diabetic Macular Edema: The BEHOLD Phase 2 and ASPIRE Phase 2b Trials. Investigative Ophthalmology & Visual Science, 2025.
43. UNITY Biotechnology. A Study to Assess the Safety and Efficacy of a Single Dose of UBX0101 in Patients With Osteoarthritis of the Knee (completed). ClinicalTrials.gov NCT04129944.
44. Mayo Clinic. Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults (AFFIRM; enrolling). ClinicalTrials.gov NCT03675724.
45. Lin G, Li X, Yie SLJ, Xu L. Clinical evidence of coenzyme Q10 pretreatment for women with diminished ovarian reserve undergoing IVF/ICSI: a systematic review and meta-analysis. Annals of Medicine, 2024.
46. Bakri S, et al. Efficacy and Safety of Coenzyme Q10 in Idiopathic Male Infertility: A Systematic Review and Meta-Analysis of Randomized Trials. World Journal of Men's Health, 2025.
47. Keum N, Chen Q-Y, Lee DH, Manson JE, Giovannucci E. Vitamin D supplementation and total cancer incidence and mortality by daily vs. infrequent large-bolus dosing strategies: a meta-analysis of randomised controlled trials. British Journal of Cancer, 2022.
48. Shahinfar H, et al. A systematic review and dose-response meta-analysis of omega-3 supplementation on cognitive function. Scientific Reports, 2025.
49. Shen J, et al. The association of serum levels of vitamin D with leucocyte telomere length, as a marker of biological aging: a meta-analysis. Medicine, 2025.
50. Tomczyk M. Omega-3 Fatty Acids and Muscle Strength — Current State of Knowledge and Future Perspectives. Nutrients, 2024.
51. Chen F, et al. Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials. Current Diabetes Reports, 2024.
52. Prokopidis K, et al. The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis. Journal of Cachexia, Sarcopenia and Muscle, 2025.
53. Yoshino M, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science, 2021.
54. Shi W, et al. High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet. Nutrients, 2019.
55. Yoshino J, Baur JA, Imai S. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metabolism, 2018.
56. Oniszczuk A. Does Resveratrol Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)? International Journal of Molecular Sciences, 2024; 25(7):3746.
57. Sergides C, et al. Bioavailability and safety study of resveratrol 500 mg tablets in healthy male and female volunteers. Experimental and Therapeutic Medicine, 2016; 11(1):164–170.