Guide to cellular vitality and healthy ageing

01  Recovery and aerobic capacity

Why recovery changes over the years

Training builds reserve: it raises the starting point and helps preserve capacity for longer.

Vitality stops being an abstract idea the moment the same weekly routine starts to demand more recovery: a hard session stays in the legs for longer, and the effort that once felt routine begins to call for planning.

One way to observe that trajectory is aerobic capacity. The Baltimore longitudinal study followed 810 healthy adults —375 women and 435 men, aged 21 to 87— and repeatedly measured their maximal oxygen uptake on a treadmill.

Physical activity does not stop the calendar, but it does change the trajectory: it preserves capacity, maintains muscle and widens the margin the body has for facing illness, immobility or periods of stress.

02  Why two people age differently

Chronological age and biological age: two rhythms that do not always match

A date of birth counts years; function counts how those years have been travelled.

Biological age attempts to describe the functional state of the body. Epigenetic clocks estimate it from DNA methylation patterns and can provide population-level information about risk and trajectory, although they should not be treated as a precision instrument that certifies a person has «grown younger» by several years.

When it comes to measuring vitality, markers of this kind have to be assessed within the wider context of functional measures such as grip strength, walking speed, aerobic capacity, body composition and the metabolic profile.

03  Cellular energy, repair and recycling

Energy, repair and recycling: the cell's everyday work

A vital cell obtains energy, repairs damage and renews its components in a continuous balance.

Ageing is built cell by cell, in the tissues and organs that make up the body. To understand it without turning it into an endless list, it helps to follow three connected jobs.

Making energy

Mitochondria turn nutrients and oxygen into ATP, the cell's energy currency. Their number, quality and capacity to adapt change with age, with movement and with metabolic state.

Repairing what breaks

DNA and proteins accumulate alterations constantly. Most are corrected by maintenance systems that consume energy and raw materials: repair is part of metabolism too.

Discarding what no longer works

Autophagy dismantles damaged proteins and worn-out cellular structures in order to reuse part of their components. It is not a longevity switch, but a normal quality-control function.

04  Inflammation, senescence and telomeres

Low-grade inflammation, senescence and telomeres

Cellular ageing is multifactorial: no single marker on its own explains how a person ages.

Low-grade inflammation

Over the years a persistent, low-intensity inflammatory tone can settle in, what is known as inflammaging. Body composition, metabolic health, movement, rest and diet all take part in that environment.

Cellular senescence

Faced with certain damage signals, a cell can enter senescence: it stops dividing but remains metabolically active. It is a defence with a cost when these cells accumulate, because they can release inflammatory signals and the body clears them less efficiently.

Telomeres

They are the caps at the end of each chromosome, comparable to the aglet on a shoelace. In many somatic cells they tend to shorten with successive divisions; when they reach a critical length, they can contribute to the cell no longer dividing.

05  Strength, sleep and diet

The foundation of cellular vitality: strength, movement, sleep and diet

Habits are not the preamble to the strategy: they are its main part.

Strength and muscle

Strength training acts at once on muscle mass, insulin sensitivity, bone density and functional capacity. Frequency, volume and progression should be adapted to the starting point, but consistency matters more than how sophisticated the programme is.

Aerobic capacity and daily movement

Walking, climbing stairs and accumulating daily activity sit alongside sessions intense enough to stimulate the heart, the vessels and the mitochondria. They are distinct, complementary layers of the same functional reserve.

Sleep, kept regular

Sleep allows repair, metabolic regulation and immune processes to consolidate. Beyond the hours, what matters is regularity, continuity and how the schedule relates to the circadian rhythm.

Enough protein and plant variety

Protein spread through the day helps sustain muscle; fibre and plant variety feed a diverse microbiota and provide a matrix of bioactive compounds. A healthy diet is not explained by a single polyphenol.

A practical proposal, in vitality routine without biohacking.

06  The role of NAD+

NAD+: a coenzyme at the crossroads of energy and maintenance

NAD+ matters because it connects several cellular functions; not because it explains ageing on its own.

Once the system is understood, the interest in NAD+ —nicotinamide adenine dinucleotide— is easier to place. It is a coenzyme described in 1906: certain reactions need it present in order to take place at all. It plays two main roles.

As a carrier: it moves electrons

It picks up electrons from what you eat and takes them to the mitochondrion to make ATP. There it is not used up: it becomes NADH and returns to NAD+.

As a substrate: it is consumed

Others use it as raw material and destroy it: PARP (repair DNA breaks), sirtuins (regulate the cellular state), CD38 (immune system).

With age, this balance can shift through changes in synthesis, recycling and consumption. Alterations of the NAD+ metabolome have been characterised in aged human muscle, with variation between tissues, health states and individuals ([4]).

What has been shown and what is being investigated

1. Can NAD+ be raised in people? Yes, in randomised placebo-controlled trials (nicotinamide riboside profile).
2. What may accompany that change? Human trials look at muscle metabolism, vascular function, insulin sensitivity, inflammation and functional capacity. The answer varies with the population, the dose and the outcome.

The useful reading is a stepwise one: first it is confirmed that the precursor reaches the pathway and raises NAD+; then it is studied in which people and contexts that change comes with functional benefits.

07  AMPK, mTOR, sirtuins and autophagy

The sensors: how the cell alternates between building and maintaining

Physical activity and energy availability modify signals that coordinate growth, adaptation and quality control.

AMPK: energy availability

It responds to a fall in available energy and favours processes that generate ATP and improve efficiency. Exercise is one of its best-known physiological stimuli.

mTOR: nutrients, growth and adaptation

It integrates signals such as amino acids, insulin and mechanical load to promote synthesis and growth. AMPK and mTOR are not a good switch and a bad one: adaptation needs to alternate between building and maintaining.

Sirtuins: the sensor that needs NAD+

They are seven enzymes involved in metabolic regulation, repair and the stress response. They use NAD+ as a substrate, connecting metabolic availability with cellular signalling.

Autophagy: quality control and recycling

Its regulation relates, among other signals, to AMPK and mTOR. In animals it can be measured directly in tissues; in people, much of the research uses indirect markers and specific experimental conditions.

08  Functional measures and biomarkers

Functional measures, blood tests and biomarkers

Each measure answers a different question: exposure, function, metabolic state or personal experience.

Three levels worth keeping apart

• Exposure. Whole-blood NAD+ makes it possible to check, in research, whether a precursor has changed the compartment being measured.
• Function. Grip strength, walking speed, aerobic capacity tests or performance describe what a person can do.
• Clinical context. Body composition, glucose, lipids and inflammatory markers complete a metabolic picture that has to be interpreted individually.

Measures that need context

• NAD+ in a specific tissue —muscle, brain or liver— requires invasive techniques such as a biopsy.
• Autophagy in a living person is studied mainly through indirect markers.
• Individual biological age is more informative as a long-term trend than as a verdict after a few weeks.
• Telomere length needs to be interpreted alongside other indicators; on its own it does not guide a decision.

09  Timeframes used in the studies

Over what timeframes changes have been studied

A trial's calendar tells you when a result was measured; it does not establish a universal timeframe for a response.

The table is there to help read the literature, not to promise a sequence of sensations. In practice, recording sleep, activity, training and one or two functional indicators under comparable conditions helps observe a trajectory without mistaking it for a single biomarker.

Timeframe	What has been measured	How to read it
1-2 weeks	In the NR dose-response trial, the rise in whole-blood NAD+ was already visible at two weeks.	It confirms a biomarker response in that population and at the doses studied.
4-8 weeks	Short trials repeat biomarkers, tolerance and, depending on the design, metabolic measures.	It shows whether the exposure is sustained; each functional result keeps its own outcome.
3-6 months	Some trials have added gait, strength, vascular function or cognition in specific populations.	The result is read within that population, that dose and that test; not as a timeline that applies to everyone.
Years	Sustained habits build functional health; longevity results call for designs and follow-ups on another scale.	Short precursor trials are not enough to translate a change in blood into years of life.

10  Compound by compound: human evidence

Compound by compound: what has been measured in people

NR has a direct dose-response curve on NAD+; other compounds add complementary evidence on metabolism, vascular function, muscle or oxidative stress.

A comparative reading of the most widely used compounds, ordered by how mature the evidence is in people.

Level	What it means
Solid	Randomised and placebo-controlled, consistent and with a large enough sample.
Promising	Real signals, but with few participants, short duration or not yet repeated.
Emerging	Early, indirect human evidence, or concentrated in specific populations.
Specific	A result valid for one particular outcome or population that should not be extrapolated without context.

A B3 vitamin from the NAD+ salvage pathway. The precursor with the most human trials.

What else is being studied. In aged human muscle, NR expanded the NAD+ metabolome; in a six-month trial with 90 people with peripheral artery disease, the NR group walked 17.6 metres further in the six-minute walk test than placebo. Other programmes are investigating metabolism, inflammation and cognition to identify which profiles respond best. Nicotinamide riboside profile.

It also acts as a precursor. In a multicentre, double-blind trial with 80 participants, 300, 600 or 900 mg daily for 60 days raised blood NAD compared with placebo at 30 and 60 days ([10]). In women with prediabetes, another trial observed an improvement in muscle insulin sensitivity ([11]). In the EU, a favourable opinion was published on 11 May 2026 on the safety of a specific β-NMN up to 300 mg daily for adults, excluding pregnancy and breastfeeding; its addition to the list of authorised novel foods was still pending when this guide was updated, and so its sale in the European Union is not permitted for the time being.

The classic form of vitamin B3 takes part in the NAD+ salvage pathway. A direct 14-day comparison in 65 participants showed a sustained rise in circulating NAD+ with NR and NMN, while nicotinamide showed a different profile ([12]). It was a randomised, open-label study whose authors were mostly linked to the company that sponsored it, which makes it especially useful as a comparative signal still to be confirmed. The flushing associated with B3 corresponds above all to niacin or nicotinic acid, a different form.

It is the reduced form of the coenzyme, not a precursor. It has been studied orally in chronic fatigue syndrome, both on its own and combined with coenzyme Q10, with favourable signals on symptoms and quality of life in small clinical samples. NADH: what it does and how it differs from NR.

It is the best-known polyphenol in grapes and one of the most studied molecules in healthy ageing. In people, the most informative reading comes from specific metabolic, vascular and cognitive results; direct SIRT1 activation remains a research mechanism.

In a 30-day trial with men with obesity, 150 mg daily were associated with changes in energy metabolism and metabolic profile consistent with a calorie-restriction response ([19]). These are promising lines that help define populations and doses; they do not turn resveratrol into a stimulant, nor do they replace exercise. Resveratrol: what it is for, scientific evidence and dosage.

A flavonoid found in onion, apple and capers. In cell models it is studied for its relationship with CD38, an enzyme that consumes NAD+; that direct link still has to be confirmed in people. The clearest human evidence is in the vascular field: a meta-analysis of randomised trials with 587 participants estimated a mean reduction of 3.04 mmHg in systolic pressure, especially at trial doses of 500 mg daily or more ([20]). It is a good example of a complementary compound: its evidence does not duplicate that of NR, it looks at another axis.

A plant alkaloid with a long history of metabolic study. In preclinical research it activates AMPK, the energy sensor described in section 07. In people, its backing is concentrated in glucose, lipids and cardiovascular factors: a systematic review and dose-response meta-analysis of clinical trials found improvements in several cardiometabolic risk markers ([34]). It is not an NAD+ precursor; within a formula it occupies a complementary route linked to the metabolic environment.

An antioxidant soluble in both water and fat that also acts as a cofactor in mitochondrial energy metabolism. Its most established clinical evidence comes from the ALADIN series and from meta-analyses in people with diabetic polyneuropathy, usually at 600 mg daily and under medical supervision. In a cellular vitality strategy it is of interest for its dual biochemical role —energy and the antioxidant network— as a complementary route, distinct from raising NAD+. Alpha-lipoic acid profile.

Vitamin B12 contributes to normal energy metabolism, to the functioning of the nervous system and to reducing tiredness and fatigue when the product meets the conditions for using those authorised claims. Measuring it is especially useful where there is a higher risk of deficiency: a vegetarian or vegan diet, older age, digestive surgery or long-term treatments such as metformin. Vitamin B12 profile.

Urolithin A can form in the gut when certain microbiotas transform the ellagitannins in foods such as pomegranate. In the reference trial, however, urolithin A itself was given, not pomegranate extract: 88 middle-aged adults over four months showed improvements in muscle strength and in biomarkers of mitochondrial health ([32]). Another trial in people over 65 observed improvements in muscle endurance and mitochondrial molecular signatures ([33]). The finding supports the interest of urolithin A; a pomegranate extract has to be judged on its own composition and evidence. Pomegranate profile.

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11  Forms and bioavailability

Forms and bioavailability: NR, NMN, niacinamide, NADH and trans-resveratrol

The chemical form, the active amount and the regulatory framework matter as much as the ingredient's name.

Standardised extract: why the total weight is not the active amount

«300 mg of Polygonum root extract» is the weight of the whole extract; the active part is a fraction. «Standardised to 98% trans-resveratrol» means that of those 300 mg, 294 are the compound. Two products with the same big number can carry very different amounts of active ingredient. Look for the standardisation percentage: how to read a supplement label.

What a trial dose means

The amounts in this guide are those of the studies, not a recommendation for use nor a description of a product. A trial with 1,000 mg daily describes what was observed at that dose; in the European Union, the authorised conditions for NR chloride in supplements set a maximum of 300 mg daily for adults.

Form	What it is	What has been measured	Trial dose	Status of use in the EU
Nicotinamide riboside	Precursor with ribose	Yes, with a dose-response curve	100-1,000 mg/day	Yes, up to 300 mg/day in supplements for adults; of NR and NMN, it is the one currently on the European list of authorised novel foods
NMN	Phosphorylated precursor	Raises circulating NAD+ in its own trials; a short direct comparison observed a response similar to NR	250-900 mg/day	Favourable European safety opinion; Commission authorisation pending as of 29 August 2026
Nicotinamide	Classic form of B3	A different profile; the direct comparison favoured NR and NMN for a sustained rise	500-1,000 mg/day	Yes
NADH	Reduced form of the coenzyme, not a precursor	Studied orally in fatigue, alone and alongside coenzyme Q10	10-20 mg/day	Yes

12  How to analyse a formula

How to analyse a cellular vitality formula

A good formula explains what each ingredient contributes, in what amount and with what level of evidence.

The NAD+ balance described in section 06 helps to understand the starting point, but a multi-ingredient formula may include actives studied for different questions. To read it properly it helps to separate three levels:

Quality is not measured by the number of ingredients either. What matters is the chemical form, the active amount, the standardisation, the function of each component, the tolerability and how simple the label is. How to read it, in forms and bioavailability; the PLENIAGE options appear at the end of the guide.

Level	What it allows you to claim	How it applies
Ingredient	A result observed with a specific substance, dose, duration and population	NR on blood NAD+; resveratrol, quercetin or berberine on their own outcomes
Rationale	Plausible complementarity between different routes	Combining a precursor with compounds studied in metabolism, vascular function or the redox environment
Complete formula	Only the results obtained when the exact combination has been evaluated as such	The coherence of the blend guides the design; it does not replace a trial of the combination

13  Precursors, IV drips and biomarkers

A map for finding your way among precursors, IV drips and biomarkers

The best option is the one that combines human evidence, a reasonable route of administration, transparency and regulatory fit.

These four questions help separate an interesting technology from a promise that runs ahead of the data.

14  Safety and interactions

Safety, precautions and interactions

NR chloride has European conditions of use and tolerance data from human trials; each combination adds its own context.

The general framework

The compounds in this guide have been studied mainly in adults and over periods that usually run from weeks to months. Those studies describe what was observed under those conditions; the duration, the population and the specific combination set the limits of how far the result can be carried across.

The limits that do exist

Nicotinamide riboside chloride is on the European list of authorised novel foods, with a maximum of 300 mg a day in supplements for adults under the corresponding conditions of use. This is not an individual recommendation nor a universal limit for any form or combination. More, in the nicotinamide riboside profile.

What has been observed in the trials

• NR chloride. In the eight-week, 140-participant trial cited in this guide, no significant differences were observed in the adverse events recorded compared with placebo. That result belongs to that substance, that duration and that population.
• Niacin and niacinamide are not the same. The flushing associated with vitamin B3 is produced by niacin (nicotinic acid), not by niacinamide.
• Polyphenols at trial doses. Far above what the diet provides; at those amounts, what is most often described is gastrointestinal discomfort.

When it is worth checking first

A food supplement does not replace or correct medical treatment. Check before starting if:

• You take anticoagulants or antiplatelet medication.
• You take medication for glucose or for blood pressure: some of these compounds have been studied precisely on those parameters, and adding effects together is not always what you want.
• You have liver or kidney disease, or you are undergoing cancer treatment.
• You are pregnant or breastfeeding: there is not enough data, and that is the reason, not a suspicion.
• You have surgery scheduled: the usual practice is to stop supplements in advance.

If new symptoms appear after starting a supplement, stop taking it and consult a healthcare professional.

The idea that keeps everything in its place

A supplement works best within a strategy that already protects sleep, strength and diet. There it can add precision and consistency, without being asked to replace what habits build.

15  Frequently asked questions

Frequently asked questions about cellular vitality and NAD+

The questions that come up most often, answered with what has been measured in people.

What does «cellular vitality» actually mean?

Can cellular ageing be looked after?

What is the difference between NR and NMN?

What is quercetin and what is known about it?

Which foods contain NAD+?

How long does it take for blood NAD+ to rise?

Which is better, NAD or NADH?

Does NAD+ have contraindications?

16  Method and references

How this guide was made

We publish the method so that it can be checked what backs each statement and how it has been interpreted.

• What goes in and what does not. What has been measured in people takes priority: randomised trials with a placebo group, systematic reviews and meta-analyses. Studies in cells and in animals are cited only to explain a mechanism, and always flagged as such — they are not used to support an effect.
• Every statement with its size. When this guide says something has been measured, it also says in how many people, for how long, at what dose and what exactly was measured. A result with eleven participants and one with three hundred are not presented the same way.
• Target and functional result, kept apart. A biomarker tells you whether a pathway has responded; a functional test answers a different question. That is why each result is presented on its own scale, without automatically turning a molecular change into a felt benefit.
• Editorial hierarchy. Each section starts with what is known and with its practical use. The caveats of population, duration and scope are presented alongside the corresponding study, so as to keep the context without turning caution into the main message.
• Trial doses, not dosage instructions. The amounts that appear in this guide are those used in the studies, because they are part of the evidence. They are not a recommendation for use and they do not describe any product.
• Dates. Anything that depends on an authorisation or an opinion is written with its date, because it changes.

Equipo de Ciencia y Nutrición PLENIAGE
Last reviewed: 30 August 2026 · Next review due: February 2027