Sirtuins: What They Are, NAD+ Link and Human Evidence

Sirtuins are a family of seven NAD+-dependent proteins (nicotinamide adenine dinucleotide) that regulate key aging processes: DNA repair, gene expression, metabolic control, and inflammation. They are identified as SIRT1 through SIRT7, each located in different cellular compartments.

In the 1990s, nobody outside yeast biology labs talked about sirtuins. Then Lenny Guarente at MIT discovered that the Sir2 gene in yeast could extend the organism's replicative lifespan. That opened a question still generating papers two decades later: do humans have something similar? The answer is yes - and it's called SIRT1.

These proteins now sit at the center of longevity medicine research. Not because they're a magic solution, but because they operate at the intersection of three central aging problems: accumulated DNA damage, low-grade chronic inflammation, and metabolic collapse.

Quick answer: activating sirtuins does not mean "rejuvenation" in a clinical sense. It means nudging cellular maintenance pathways — DNA repair, inflammation control, mitochondrial metabolism and stress response — that depend on enough NAD+. The evidence is strong in molecular biology and animal models; in humans, the honest outcome is biomarkers and metabolic health, not proven extra years of life.

Last scientific review: June 2026.

Known	Plausible	Not established
Sirtuins are NAD+-dependent regulators of repair, metabolism, inflammation and stress response.	Exercise, well-indicated caloric restriction and NAD+ precursors may support pathways involving SIRT1, SIRT3 or SIRT6.	No human trial proves that activating sirtuins extends lifespan or clinically rejuvenates tissues.
NMN/NR raise NAD+-related metabolites in several human trials.	That increase could support NAD+-dependent reactions in certain tissues and subgroups.	Raising blood NAD+ does not prove direct sirtuin activation or universal clinical benefit.
Routine direct measurement of SIRT1-7 activity is not an established clinical biomarker.	The pathway context can be inferred from inflammation, glucose, body composition, VO₂max and recovery.	A standalone NAD+/NADH value does not diagnose biological age or decide an intervention by itself.

Before Buying a "Sirtuin Activator": Five Filters

Commercial content often jumps from “SIRT1 is involved in longevity” to “this supplement rejuvenates you.” That is where the science gets lost. Before taking action, run any claim through this table:

Filter	Useful question	Why it changes the reading
Evidence type	Is it cell, animal, healthy human or patient data?	An effect in yeast or mice is not the same as a clinical benefit in a person.
Actual measurement	Was SIRT activity measured, or only blood NAD+?	Raising a metabolite does not prove that SIRT1, SIRT3 or SIRT6 work better in the target tissue.
Target tissue	Is the question muscle, liver, fat, brain or blood?	The NAD+/sirtuin axis is tissue-specific; one blood value can oversimplify the picture.
Clinical endpoint	Did anything meaningful improve: strength, VO₂max, glucose, inflammation, sleep or symptoms?	Clinical longevity is built on measurable function and risk, not on an isolated molecular pathway.
Safety	Is there active cancer, anticoagulant use, pregnancy, liver or kidney disease, or complex medication?	“Natural” compounds can still interact; more dose does not mean more health.

What They Are (and What They're Not)

The name can confuse. Sirtuins are NAD+-dependent histone deacetylases, but that doesn't make them simply "enzymes that remove acetyl groups from histones." They do that - but they also act on non-histone proteins: transcription factors, metabolic enzymes, DNA repair proteins.

The technical difference from conventional histone deacetylases is the cofactor. Classic HDACs (classes I, II, and IV) don't need NAD+ to function. Sirtuins do. That NAD+ dependency makes them metabolic sensors: in cellular and animal models, when NAD+ is available, many SIRT pathways can operate better; when NAD+ is scarce in a specific tissue, their potential activity falls.

Massudi et al. (PLoS One, 2012, PMID: 22848760) found that NAD+ levels in human pelvic skin samples fall approximately 50% between ages 40 and 60. That is a specific tissue finding, not a whole-body measurement. In fact, Trętowicz et al. (Nature Metabolism, 2026, DOI: 10.1038/s42255-026-01537-5) found no consistent variation in whole-blood NAD+ with age or lifestyle interventions, and a comment in the same issue put it plainly: “whole-blood NAD+ levels do not reflect healthy ageing.” Clinical translation: NAD+/sirtuin metabolism is tissue-specific and cannot be interpreted from one blood tube alone.

The 7 Sirtuin Types and What Each Does

Sirtuin	Cellular location	Main function
SIRT1	Nucleus / cytoplasm	Deacetylates histones and transcription factors like p53 and NF-κB. Regulates autophagy, insulin sensitivity, and inflammatory response. The most studied sirtuin.
SIRT2	Cytoplasm	Cell cycle stability. Regulates mitotic progression and adipocyte differentiation. Implicated in neurodegenerative diseases.
SIRT3	Mitochondria	Main mitochondrial deacetylase. Activates antioxidant enzymes (SOD2), regulates ATP, mitophagy and fatty-acid metabolism. Central to mitochondrial resilience.
SIRT4	Mitochondria	Regulates amino acid and fatty acid metabolism. A tumor suppressor in certain contexts.
SIRT5	Mitochondria	Desuccinylase, demalonylase and deglutarylase. Regulates amino acid catabolism, the urea cycle, fatty-acid oxidation and redox balance.
SIRT6	Nucleus	Repairs DNA double-strand breaks, maintains telomeres, regulates glycolysis and autophagy. In specific mouse models, increasing SIRT6 extends male median lifespan by roughly 15-20%.
SIRT7	Nucleolus	Regulates ribosomal RNA transcription and protein synthesis. Involved in genomic stability and DNA damage response.

SIRT1 and SIRT6 capture most longevity research attention. SIRT3 is most relevant for mitochondrial function. In the aging context, the cautious model is that changes in NAD+ availability and in some sirtuin pathways, depending on tissue and metabolic context, may contribute to several of the cellular deterioration mechanisms that define aging.

Why They're Called "Longevity Proteins"

The name comes from the original experiments. In yeast, Sir2 overexpression extended replicative lifespan by around 30%. In C. elegans (the nematode worm), similar manipulations of the sir-2.1 gene produced lifespan extensions of up to 50% in some experimental conditions.

The jump to mammals was more complex. In mice, SIRT6 overexpression extends median lifespan in males by 15% (Kanfi Y et al., Nature, 2012, PMID: 22367546). The extension hasn't been seen with the same consistency across all models, which led to a prolonged scientific debate about whether simple-organism effects translate directly to mammals.

Sinclair and Guarente, in a review that remains a field reference (Scientific American, 2006, PMID: 16502611), argued that caloric restriction - the most consistently life-extending intervention from yeast to mammals - works partly through sirtuin-related pathways. The idea: when fewer calories are available, the NAD+/NADH state shifts and sirtuin-dependent maintenance programs may have more room to operate.

Not everyone shares that reading in its strongest form. Charles Brenner, writing in Life Metabolism (2022, DOI: 10.1093/lifemeta/loac025; PMID: 37035412), made the opposing case directly: sirtuins should not be treated as “conserved longevity genes” because yeast, worm, fly, mouse and human genetics do not form a clean line. His critique does not mean NAD+ and sirtuins are unimportant; it means we should separate NAD+ metabolism from the simplified promise that “activating sirtuins = living longer.”

The middle-ground reading is the most useful one: sirtuins are important maintenance enzymes in aging biology, but they are not a single longevity switch. Any clinical claim has to move from mechanism to measured human outcome.

What the Evidence Says in 2026: Strong Mechanisms, Careful Human Claims

To interpret sirtuins well, separate evidence levels. Showing that SIRT6 repairs DNA in a cell is not the same as showing that a supplement extends human lifespan.

Question	Evidence status	Practical reading
Do sirtuins regulate aging-relevant processes?	High in molecular biology	SIRT1, SIRT3 and SIRT6 participate in inflammation, mitochondria, DNA repair, telomeres and stress response.
Does increasing them extend lifespan?	Strong in simple organisms; moderate and model-dependent in mice	There are clear signals, but they do not translate linearly to humans.
Does raising NAD+ improve sirtuin activity in humans?	Moderate for raising NAD+; limited for directly measuring sirtuin activity	NMN and NR raise NAD+-related metabolites in several trials, but clinical effects and direct sirtuin measurement remain variable.
Is there proof of human lifespan extension?	Not demonstrated	The reasonable clinical use case is optimizing metabolism, inflammation and mitochondrial function, not promising extra years.

The relevant 2025-2026 update is that the field has moved beyond SIRT1 and resveratrol alone. A 2025 Advanced Biology review of SIRT6 summarizes its role in DNA repair, telomeres, oxidative stress and autophagy. 2025 reviews of SIRT3 and the mitochondrial sirtuins (SIRT3, SIRT4 and SIRT5) reinforce their role in bioenergetics, ROS handling and mitochondrial quality control. At the same time, Vinten et al. (Nature Metabolism, 2025, PMID: 41083806) warn that evidence for an age-related NAD+ decline in humans is consistent only in a limited number of studies and that rodent-to-human tissue extrapolation is not straightforward.

The most useful human clue comes from adipose tissue. Lapatto et al. (International Journal of Obesity, 2026, PMID: 41491271) studied monozygotic twin pairs discordant for BMI and found that obesity and aging were associated with changes in NAD+/sirtuin metabolism genes: SIRT5 and NRK1 were lower in both contexts; in obesity, SIRT1 and SIRT3 were also lower. Clinical translation: body composition, visceral fat and inflammation matter as much as the supplement of the month.

Their Role in Aging: Three Mechanisms

1. DNA repair and genomic stability

SIRT1 and SIRT6 are directly recruited to DNA damage sites. SIRT6 deacetylates histone H3K56, facilitating the response to double-strand breaks - the most dangerous type, because if not properly repaired they can lead to mutations or senescence. In mouse models with inactivated SIRT6, animals develop an accelerated aging phenotype with marked genomic instability (Mostoslavsky R et al., Cell, 2006, PMID: 16439206).

This function connects directly to genomic instability as the first hallmark of aging per López-Otín et al. (Cell, 2023, PMID: 36599349).

2. Metabolic control and inflammation

SIRT1 deacetylates NF-κB - the master inflammation switch - reducing its transcriptional activity. It also activates PGC-1α, the main regulator of mitochondrial biogenesis. In practical terms: when SIRT1 works well, there's less chronic inflammation and more healthy mitochondria generating energy efficiently.

De Cabo and Mattson reviewed in NEJM (2019, PMID: 31881139) the molecular mechanisms of intermittent fasting. A central part of their analysis: fasting can change cellular energy state, including NAD+ biology, and is linked to pathways where SIRT1 and SIRT3 participate. In humans, the best-supported outcomes are changes in weight, insulin sensitivity, blood pressure or inflammatory markers in selected profiles; direct measurement of tissue SIRT activity is much less common.

3. Epigenetics and gene expression

Sirtuins modify chromatin state by deacetylating histones, changing which genes are expressed and which aren't. With age, epigenetic patterns become disorganized - one of the central hallmarks of aging per López-Otín. Active sirtuins help maintain those patterns in order. When their activity falls, genes that should be silenced become active, and vice versa.

NAD+ and Sirtuins: The Connection You Can't Ignore

If you've read our post on NAD+ therapy, you already have half the story. Sirtuins are useless without NAD+: they need to consume NAD+ to carry out their deacetylation reactions. Every time SIRT1 deacetylates a protein, it consumes one NAD+ molecule and produces nicotinamide (which can then be recycled back to NAD+ or inhibit SIRT1 activity at high concentrations).

That's why NAD+ precursors - NMN and NR - generate such interest in the longevity field. The hypothesis: if we raise NAD+ levels, we give sirtuins more "fuel" to do their cellular maintenance work.

Igarashi et al. (NPJ Aging, 2022, PMID: 35927255) showed in healthy older men that oral NMN raised blood NAD+ and altered muscle-function markers, without directly measuring sirtuin activity. Yoshino et al. (Science, 2021, PMID: 33888596) reported improved insulin sensitivity in postmenopausal women with prediabetes after NMN. The honest reading is this: NAD+ precursors can move biomarkers in specific subgroups, but they do not yet prove rejuvenation or human lifespan extension.

Intervention	Human population studied	What it measured	Direct SIRT activity?	Clinical reading
Oral NMN	Healthy older men; postmenopausal women with prediabetes in separate trials	Blood NAD+, muscle or insulin-sensitivity markers	No routine direct tissue SIRT measurement	Promising metabolic signal in specific profiles, not proof of lifespan extension.
Oral NR	Healthy adults and selected disease or risk groups	NAD+-related metabolites, safety and selected metabolic endpoints	Usually indirect	Good biochemical target engagement; clinical effects remain variable.
Intravenous NAD+	Small pharmacokinetic pilot data, not anti-aging outcomes trials	Plasma and urine NAD+ metabolites after infusion	No	Useful medical route in selected contexts; not evidence of rejuvenation by itself.

At Progevita, NAD+ IV therapy may be used within longevity programs such as Inflammaging (from €1,470), but the claim needs precision: IV delivery is a medical tool for a monitored setting, not proof of rejuvenation. Grant et al. (Frontiers in Aging Neuroscience, 2019, PMID: 31572171) published a 6-hour NAD+ infusion pharmacokinetic pilot, useful for understanding plasma and urine metabolites. A 2026 PRISMA review (Gallagher et al., Ageing Research Reviews, PMID: 41655607) concluded that oral NR/NMN show biochemical target engagement in humans, while no clinical outcomes trials evaluate intravenous NAD+ for anti-aging or wellness indications. Zhang et al. (Nature Aging, 2025, DOI: 10.1038/s43587-025-00947-6) frame the field similarly: strong clinical potential, but unresolved issues around dosing, target tissue, safety, endpoints and patient selection.

That is why our standard is not “more NAD+ is always better.” It is to evaluate inflammation, glucose, body composition, mitochondrial function and contraindications first; only then decide whether IV NAD+, oral precursors, exercise, nutrition or sleep interventions make sense for that person.

How Fasting and Exercise Support Sirtuin Pathways

You don't need a clinic to influence pathways involving sirtuins. Two interventions with broad evidence have plausible mechanistic effects; direct measurement of SIRT1/SIRT3 activity in human tissues, however, remains limited:

Intermittent fasting

When caloric availability drops, the NAD+/NADH ratio may shift and modulate energy-response programs. De Cabo and Mattson (NEJM, 2019) described how fasting - whether 16:8 or alternate-day fasting - relates to SIRT1/SIRT3 pathways in animal models, with physiological correlates in humans including changes in weight, insulin or inflammatory markers depending on the profile. That is not the same as measuring tissue “rejuvenation” in humans.

The mechanism doesn't operate in isolation: fasting also activates AMPK (which inhibits mTOR) and autophagy. Sirtuins are part of that response ensemble, not the only actor.

Physical exercise

Exercise - especially aerobic work in zone 2 - increases NAD+ turnover in muscle and may stimulate synthesis and recycling pathways. Through AMPK and PGC-1α, it is linked to pathways involving SIRT1 and mitochondrial sirtuins, although direct human tissue-activity evidence is thinner than the mechanistic evidence. A review by Radak et al. (Free Radical Biology and Medicine, 2013, PMID: 23339850) describes how regular exercise involves sirtuin-regulated pathways: antioxidant defense, macromolecular damage repair, mitochondrial function and neuronal plasticity.

This connects to something we measure directly at Progevita: VO₂max, one of the strongest markers of cardiorespiratory capacity and cardiovascular risk. Zone 2 training that improves VO₂max also engages mitochondrial pathways where sirtuins such as SIRT3 participate. It is not a coincidence that the interventions most consistently associated with long-term health - aerobic exercise and well-indicated caloric restriction - overlap with sirtuin-related signaling.

Foods Containing Sirtuin-Activating Compounds

The "sirtfood diet" popularized by Aidan Goggins and Glen Matten mixes real science with marketing. The real science: several plant compounds may modulate SIRT1 or related pathways in cellular and animal models. The marketing: turning that into a miracle diet with Adele on the cover.

Foods do not contain sirtuins in a form your body can use; they contain polyphenols that may modulate pathways involving SIRT1, AMPK, NF-κB and oxidative stress. That distinction matters: blueberries or green tea can be part of a metabolically healthy diet, but they do not let you “switch on longevity genes” at will.

The compounds with the strongest evidence base:

Compound	What we know	What we should not promise
Resveratrol	Small human signals on AMPK/SIRT1/PGC-1α and metabolic markers at supplement doses.	It does not justify drinking wine or prove human longevity.
EGCG	May modulate inflammation and oxidative stress; glycemic results are mixed.	It does not guarantee clinical SIRT1 activation.
Quercetin/fisetin	Senolytic data exist in models and very specific preliminary human studies.	They are not ready-made anti-aging self-medication protocols.

Resveratrol (red wine, grapes, blueberries)

Resveratrol was for years the most studied longevity molecule, largely because early work linked it to SIRT1 in cellular and animal models. In humans, the classic trial by Timmers et al. (Cell Metabolism, 2011, PMID: 22055504) used 150 mg/day for 30 days in 11 men with obesity and reported AMPK activation, higher SIRT1/PGC-1α protein levels in muscle and metabolic improvements. Interesting, yes; definitive, no. It supports research, not resveratrol as a proven human longevity intervention.

EGCG (green tea catechins)

Epigallocatechin gallate (EGCG) modulates SIRT1, NF-κB and oxidative stress in experimental models. In humans, the reading is more cautious: green tea meta-analyses show signals on inflammatory mediators such as CRP in some contexts (Haghighatdoost and Hariri, Phytotherapy Research, 2019, PMID: 31309655), while glycemic control and HOMA-IR in type 2 diabetes show null or mixed results in trial reviews (Asbaghi et al., 2021, PMID: 33285391). Good food; plausible mechanism; not guaranteed clinical “SIRT1 activation.”

Quercetin (onions, capers, apples)

Quercetin modulates SIRT1-related pathways in models and appears in senolytic protocols alongside dasatinib. Precision matters: Hickson et al. (EBioMedicine, 2019, PMID: 31542391) published preliminary data with dasatinib + quercetin in diabetic kidney disease, not quercetin alone in healthy adults. Dasatinib is a prescription drug, and quercetin can interact with anticoagulants, antiplatelet therapy and liver drug metabolism. Genuine potential, yes; anti-aging self-medication, no.

Fisetin (strawberries, apples)

Less well-known than resveratrol, with interesting animal-model data. Yousefzadeh et al. (EBioMedicine, 2018, PMID: 30279143) showed a 10% extension of median lifespan in fisetin-treated mice, alongside lower senescent-cell burden. The honest translation: promising senolytic hypothesis, not yet a proven human longevity intervention.

Supplements, Promises and Safety: What to Watch

Most commercial results around sirtuins stop at “eat these foods” or “take this NAD+ precursor.” A clinical reading asks a sharper question: which intervention moves which pathway, with what human evidence and with what limit?

Intervention	Pathway affected	Clinical nuance
Aerobic exercise + strength training	AMPK, PGC-1α, SIRT1/SIRT3, mitochondrial biogenesis	Best human translation because it also improves VO₂max, muscle mass, glucose and inflammation.
Fasting or supervised caloric restriction	NAD+/NADH, SIRT1/SIRT3, autophagy, mTOR	Can help, but is not appropriate in frailty, low weight, eating disorders, pregnancy or athletes with low energy availability.
NMN/NR or IV NAD+	NAD+ availability for sirtuins, PARP and CD38	Promising for biomarkers; not yet proof of human longevity. Needs medical context when disease, medication or active cancer is present.
Polyphenols: resveratrol, EGCG, quercetin, fisetin	SIRT1, NF-κB, oxidative stress, senescence in models	Better as part of a plant-rich diet than as high-dose supplementation without follow-up.

Safety matters because sirtuins are not “anti-aging” switches. They participate in DNA repair, metabolism, inflammation and also context-dependent tumor biology. In people with active cancer, significant liver or kidney disease, oncology treatment, anticoagulants, pregnancy or complex medication, pursuing sirtuin activation with supplements without medical supervision makes little sense.

What Progevita Does With This

Knowing about sirtuins is useful. Knowing whether your metabolism gives them the conditions to work well is better. Clinically, we do not measure "SIRT1 activity" the way we measure cholesterol; we combine direct and indirect markers that map the NAD+/sirtuin pathway.

Marker	What it tells us	Why it matters for sirtuins
NAD+/NADH — only when available with well-controlled sampling and method	Potential availability of the substrate sirtuins consume	Not a validated biomarker of aging or SIRT activity: whole blood, plasma and tissue may tell different stories.
hs-CRP, suPAR, insulin and HOMA-IR	Inflammatory and metabolic load	Inflammation, insulin resistance and visceral fat are associated with lower SIRT1/SIRT3 signaling.
VO₂max and HRV	Mitochondrial capacity and autonomic resilience	Training that improves these markers is associated with AMPK, PGC-1α and mitochondrial pathways involving sirtuins.
Body composition and visceral fat	The tissue context where NAD+/sirtuin signaling plays out	The 2026 twin study links obesity and age with lower expression of several NAD+/SIRT genes in adipose tissue.

From that evaluation, the protocol may include intravenous NAD+ infusions, adjustments in exercise toward more zone 2 aerobic work, and nutritional interventions with polyphenolic compounds. Progevita offers NAD+ IV in selected programs, but does not present it as proven rejuvenation or lifespan extension. The priority is not to “activate SIRT1” in the abstract; it is to correct the measurable bottleneck - inflammation, insulin resistance, visceral fat, low aerobic capacity, sleep or recovery - within a program that also addresses the other aging determinants.

If you want to know where your sirtuins metaphorically stand - meaning, whether your metabolism has the conditions for them to work well - the starting point is a biomarker evaluation with our medical team.

To see how that translates into care, explore our treatments, Optimization, Inflammaging and about page.

Frequently Asked Questions About Sirtuins

What exactly are sirtuins?

Sirtuins are a family of seven proteins (SIRT1-7) that function as NAD+-dependent enzymes. They regulate cellular processes like DNA repair, metabolic control, inflammatory response, and gene expression. In some tissues and aging contexts, their activity or expression may decline alongside NAD+ biology; it is not a uniform whole-blood marker.

Why are they called "longevity proteins"?

The name comes from experiments showing that sirtuin overexpression extends lifespan in yeast, C. elegans, and mice. The connection to caloric restriction - the most reproducible longevity intervention - also involves sirtuin-related pathways. In humans, direct lifespan extension evidence is still indirect, but their role in cellular maintenance is well documented.

How can sirtuins be activated?

The approaches with the best evidence base are: intermittent fasting or well-indicated caloric restriction, regular aerobic exercise, strength training, and NAD+ support through precursors such as NMN or NR when clinically appropriate. These interventions are linked to pathways where SIRT1, SIRT3 and other sirtuins participate, but direct human tissue activation is rarely measured. Compounds like resveratrol and EGCG have plausible mechanisms in experimental models, though human evidence is more modest.

What's the difference between sirtuins and conventional histone deacetylases?

Sirtuins are class III histone deacetylases. The fundamental difference is that they depend on NAD+ as a cofactor, while conventional HDACs (classes I, II, and IV) don't. That NAD+ dependency makes them sensors of the cell's metabolic state - something conventional HDACs don't do.

Are sirtuins and NAD+ the same thing?

No. Sirtuins are enzymatic proteins. NAD+ is the coenzyme they need to function. The relationship is substrate-enzyme: sirtuins consume NAD+ to execute their reactions. Without sufficient NAD+, sirtuins can't work well even if present in the cell. That's why NAD+ therapy aims to restore that substrate.

Do foods contain sirtuins?

Not in a practical sense. Foods contain polyphenols — such as resveratrol, EGCG, quercetin or fisetin — that may modulate pathways where sirtuins participate. It is more accurate to speak of foods that support a favorable metabolic context than foods that “contain sirtuins.”

Is there evidence that activating sirtuins extends human lifespan?

Not directly. Lifespan extension evidence comes from yeast, worms, flies and some mouse models. In humans, there are trials where NR or NMN raise NAD+ and improve selected markers in specific subgroups, but that is not the same as proving longer life. The careful reading is to improve cellular maintenance pathways and measure clinical outcomes.

Can sirtuin activity be measured in a blood test?

Not as a routine biomarker comparable to cholesterol, ApoB or HbA1c. Research can measure enzyme activity, gene expression or proteomic changes, but clinically it is usually more useful to contextualize the pathway with carefully sampled NAD+/NADH when appropriate, inflammation, insulin, body composition, VO₂max, strength, sleep and recovery.

Does the resveratrol in red wine activate sirtuins?

Red wine contains resveratrol, but in very low amounts - between 0.5 and 3 mg per glass. Studies showing SIRT1 modulation usually use 150-500 mg/day doses of supplemental resveratrol. Drinking wine for the resveratrol makes no biological sense: the alcohol damages more pathways than resveratrol can support at that dose. EGCG from green tea is a more accessible dietary polyphenol linked to these pathways.

When should I consult a doctor about sirtuins?

If you want to evaluate your metabolic state in relation to sirtuin activity - NAD+/NADH, systemic inflammation, body composition - it makes sense to do so with a medical team that can interpret results in context. High-dose NMN or NR supplementation should be reviewed with a professional, especially if there are underlying health conditions.

References

1. Sinclair DA, Guarente L, "Unlocking the secrets of longevity genes", Scientific American, 2006 (PMID: 16502611)
2. Brenner C, "Sirtuins are not conserved longevity genes", Life Metabolism, 2022 (PMID: 37035412; DOI: 10.1093/lifemeta/loac025)
3. de Cabo R, Mattson MP, "Effects of Intermittent Fasting on Health, Aging, and Disease", N Engl J Med, 2019 (PMID: 31881139)
4. López-Otín C et al., "Hallmarks of aging: An expanding universe", Cell, 2023 (PMID: 36599349)
5. Massudi H et al., "Age-associated changes in oxidative stress and NAD+ metabolism in human tissue", PLoS One, 2012 (PMID: 22848760)
6. Kanfi Y et al., "The sirtuin SIRT6 regulates lifespan in male mice", Nature, 2012 (PMID: 22367546)
7. Mostoslavsky R et al., "Genomic instability and aging-like phenotype in the absence of mammalian SIRT6", Cell, 2006 (PMID: 16439206)
8. Yoshino M et al., "Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women", Science, 2021 (PMID: 33888596)
9. Igarashi M et al., "Chronic nicotinamide mononucleotide supplementation elevates blood NAD+ levels", NPJ Aging, 2022 (PMID: 35927255)
10. Radak Z et al., "Redox-regulating sirtuins in aging, caloric restriction, and exercise", Free Radical Biology and Medicine, 2013 (PMID: 23339850)
11. Yousefzadeh MJ et al., "Fisetin is a senotherapeutic that extends health and lifespan", EBioMedicine, 2018 (PMID: 30279143)
12. Katsyuba E et al., "NAD+ homeostasis in health and disease", Nat Metab, 2020 (PMID: 32694684)
13. Lu Y et al., "The Role and Molecular Pathways of SIRT6 in Senescence and Age-related Diseases", Adv Biol, 2025 (PMID: 39913122)
14. Ji Z et al., "Mitochondrial sirtuins, key regulators of aging", Life Med, 2025 (PMID: 40799515)
15. You Y, Wang Z, "Roles of SIRT3 in aging and aging-related diseases", Int J Biol Sci, 2025 (PMID: 40860195)
16. Lapatto HAK et al., "The effect of obesity and aging on NAD+/Sirtuin metabolism transcription and DNA methylation in subcutaneous adipose tissue", Int J Obes, 2026 (PMID: 41491271)
17. Bohr VA, "Promising Results With NAD Supplementation in Rare Diseases With Premature Aging and DNA Damage", Aging Cell, 2026 (PMID: 41436848)
18. 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 (PMID: 41655607)
19. Vinten KT et al., "NAD+ precursor supplementation in human ageing: clinical evidence and challenges", Nature Metabolism, 2025 (PMID: 41083806)
20. Trętowicz P et al., "Human whole-blood NAD+ levels do not vary with age or lifestyle interventions", Nature Metabolism, 2026 (DOI: 10.1038/s42255-026-01537-5)
21. Zhang J et al., "Emerging strategies, applications and challenges of targeting NAD+ in the clinic", Nature Aging, 2025 (DOI: 10.1038/s43587-025-00947-6)
22. Grant R et al., "A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD", Frontiers in Aging Neuroscience, 2019 (PMID: 31572171)
23. Timmers S et al., "Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans", Cell Metabolism, 2011 (PMID: 22055504)
24. Haghighatdoost F, Hariri M, "The effect of green tea on inflammatory mediators", Phytotherapy Research, 2019 (PMID: 31309655)
25. Asbaghi O et al., "Effect of green tea on glycemic control in patients with type 2 diabetes mellitus", Diabetes & Metabolic Syndrome, 2021 (PMID: 33285391)
26. Hickson LJ et al., "Senolytics decrease senescent cells in humans", EBioMedicine, 2019 (PMID: 31542391)

This article is for informational purposes and does not replace individual medical consultation. NAD+ precursors, intravenous NAD+ and high-dose polyphenols should be considered only with clear goals, contraindication review and follow-up; none should be presented as proven rejuvenation or lifespan extension.

Want to know if your metabolism has the conditions for sirtuins to work well? Talk to our medical team and design a personalized protocol at Balneario de Cofrentes, Valencia.