Epitalon vs NAD+: A Telomere Peptide and an Energy Molecule, Two Very Different Routes Into Ageing Research

Here are two of the most searched names in longevity research, and they could hardly be more different. One is a four-amino-acid peptide born in a Soviet military research programme, designed to switch on an enzyme that rebuilds the protective caps on the ends of chromosomes. The other is a molecule so fundamental that every living cell on Earth depends on it, first spotted more than a century ago by two British chemists trying to understand why yeast ferments sugar.

Epitalon and NAD+ are often mentioned in the same breath because both sit at the centre of ageing research. But they approach it from opposite ends: one through the chromosome, the other through the cell’s energy supply. This guide explains where each came from, what the key studies found, how they differ in mechanism, and how researchers decide which one fits a particular question. Both are supplied by Crown Peptides for laboratory research use only.

Why Ageing Research Has So Many Starting Points

Ageing is not one process. In 2013, a much-cited paper in the journal Cell by López-Otín and colleagues grouped the biology of ageing into a set of “hallmarks”, distinct but interconnected processes that together drive the changes we see as cells and organisms grow older. The list has since been expanded, but two of the original hallmarks are directly relevant here.

One is telomere attrition: the gradual shortening of the protective caps on the ends of chromosomes each time a cell divides. The other is mitochondrial dysfunction and the closely linked problem of deregulated nutrient sensing: the decline in how well cells produce energy and respond to their metabolic state. Epitalon’s research lives mostly in the first. NAD+’s lives mostly in the second. That single distinction explains most of the comparison.

Epitalon: A Peptide From the Pineal Gland Programme

Epitalon, also spelled Epithalon, is a synthetic peptide made of just four amino acids: alanine, glutamic acid, aspartic acid and glycine, written Ala-Glu-Asp-Gly or AEDG. Both spellings refer to exactly the same compound.

From an extract to a sequence

Epitalon’s story begins in the 1970s with Vladimir Khavinson, a military doctor working at the Kirov Military Medical Academy in Leningrad. His team was developing ways to protect and restore the health of personnel exposed to extreme stress, and their approach was to extract mixtures of short peptides from specific animal organs and test whether they helped the matching organ in the recipient.

One of those extracts came from the pineal gland, the small structure deep in the brain that produces melatonin and helps govern the body’s daily rhythms. It was called Epithalamin. Later, after Khavinson founded the Saint Petersburg Institute of Bioregulation and Gerontology in 1992, the team analysed the extract’s amino acid composition and designed a short synthetic peptide to capture its activity. That peptide was Epitalon.

Moving from an animal extract to a precisely defined four-amino-acid sequence was a crucial step. It meant the compound could be made synthetically, reproducibly and at high purity, which is exactly what modern research requires.

The telomerase finding

Epitalon’s reputation rests largely on a pair of short papers from the early 2000s. In 2003, Khavinson and colleagues reported in the Bulletin of Experimental Biology and Medicine that adding Epitalon to cultures of human fetal fibroblasts, cells that normally lack active telomerase, induced expression of the enzyme’s catalytic subunit, switched on telomerase activity and led to telomere elongation (PMID: 12937682).

A year later, the same group reported a follow-up in the same journal (PMID: 15455129). Human lung fibroblasts from a fetus normally stopped dividing at around their 34th passage, the point at which their telomeres had become short. When Epitalon was added to these ageing cultures, telomeres lengthened to a size comparable to that seen in young cultures, and the treated cells went on to make ten extra divisions beyond the control cells and kept dividing. The authors described this as the cells overcoming the Hayflick limit, the natural ceiling on how many times a normal cell can divide.

The melatonin connection

Because Epitalon was derived from a pineal extract, the Saint Petersburg group also studied its effects on melatonin, the hormone the pineal gland releases at night. Melatonin production and the strength of its day-night rhythm both decline with age, in monkeys as in people.

In a study of rhesus macaques published in Advances in Gerontology in 2003, Goncharova, Khavinson and colleagues compared young females aged 6 to 8 with older females aged 20 to 26 (PMID: 14743609). The older monkeys’ average daily melatonin was 1.5 to 2 times lower, with the biggest gaps in the night-time peak. A short course of Epitalon or Epithalamin produced a significant increase in night-time plasma melatonin in the older monkeys, while leaving melatonin levels in the young monkeys unchanged. That pattern, restoring a declining signal without pushing a healthy one higher, is exactly what makes it interesting to ageing researchers. A later review from the same research network described similar normalisation of the daily melatonin rhythm in older people with reduced pineal function (PMID: 17969590).

The lifespan study in mice

The most ambitious Epitalon study looked at whole animals across their entire lives. In 2003, Anisimov, Khavinson and colleagues at the N.N. Petrov Institute of Oncology in Saint Petersburg published the results in Biogerontology (PMID: 14501183). Female mice received Epitalon or saline for five consecutive days each month, from three months of age until their natural deaths.

The results were nuanced and genuinely interesting. Mean lifespan was not changed. But the longest-lived animals lived longer: the lifespan of the last 10% of survivors increased by 13.3% and maximum lifespan by 12.3% compared with controls. Epitalon slowed the age-related switching-off of reproductive cycling, reduced chromosome aberrations in bone marrow cells by 17.1%, and, while it did not change total tumour incidence, the development of leukaemia was six times lower than in the control group. The authors concluded the results suggested geroprotective activity and supported the safety of long-term administration in mice.

For a deeper look at Epitalon’s full research history, see our Epitalon research guide.

NAD+: The Molecule Every Cell Runs On

NAD+, or nicotinamide adenine dinucleotide, is not a peptide at all. It is a coenzyme, a helper molecule that enzymes need in order to work, built from two nucleotides joined together. It is found in every living cell, from bacteria to humans, and without it life as we know it could not happen.

A discovery that started with beer yeast

In 1906, the British chemists Arthur Harden and William John Young were studying fermentation, the process by which yeast turns sugar into alcohol. They found that yeast juice contained a heat-stable factor, which they called a “coferment”, that was essential for fermentation to proceed. That factor was NAD. Harden shared the 1929 Nobel Prize in Chemistry for work on fermentation.

Over the following decades, a string of discoveries revealed how central the molecule is. In the 1930s, Otto Warburg showed that it carries hydrogen atoms, and with them electrons, from one chemical reaction to another. In 1937, Conrad Elvehjem discovered that nicotinic acid, now called niacin or vitamin B3, cured pellagra, a devastating deficiency disease, and it later became clear that niacin’s job in the body is largely to make NAD.

Two jobs, both essential

NAD+ has two main roles. The first is as an energy carrier. In the reactions that break down sugars and fats, NAD+ picks up electrons and becomes NADH, which then delivers them to the mitochondria, where they drive the production of ATP, the cell’s energy currency. This role recycles NAD+ rather than using it up.

The second role is as a fuel for signalling enzymes, and this is where ageing research comes in. Several families of enzymes consume NAD+ as they work, breaking it apart. The most famous are the sirtuins, enzymes involved in regulating metabolism, stress responses and gene activity; the PARPs, which help repair damaged DNA; and CD38, an enzyme found on immune cells and elsewhere.

The discovery that linked NAD+ to ageing

For most of the twentieth century, NAD+ was seen as a housekeeping molecule, essential but unremarkable. That changed in 2000. Working in Leonard Guarente’s laboratory at MIT, Shin-ichiro Imai and colleagues were studying Sir2, a yeast protein known to silence genes near telomeres and to extend the replicative lifespan of yeast cells. In a paper in Nature, they showed that both yeast Sir2 and its mouse counterpart are NAD-dependent histone deacetylases: enzymes that remove chemical tags from the proteins DNA is wrapped around, and that can only do so by consuming NAD+ (PMID: 10693811).

The authors pointed out what this meant. It gave a molecular framework connecting metabolism, gene silencing and ageing, because an enzyme that controls lifespan in yeast depends directly on the cell’s supply of a metabolic coenzyme. The sirtuin family, as Sir2 and its relatives became known, launched an entire field, and it is the reason NAD+ is now one of the most studied molecules in ageing research. There is a neat irony here for anyone comparing Epitalon and NAD+: Sir2 was first studied partly because it silences genes near telomeres, the very structures at the centre of Epitalon’s research.

The age-related decline

A key finding of the past two decades is that NAD+ levels fall with age in many tissues. In a 2014 review in Trends in Cell Biology, Shin-ichiro Imai and Leonard Guarente described NAD+ decline during ageing as a potential “Achilles’ heel”, causing defects in nuclear and mitochondrial functions, and summarised research in which restoring NAD+ with its precursors ameliorated age-associated functional defects in animal models (PMID: 24786309, PMC4112140).

Why does it fall? A 2016 study in Cell Metabolism by Camacho-Pereira, Chini and colleagues at the Mayo Clinic provided a major part of the answer (PMID: 27304511, PMC4911708). They found that the expression and activity of CD38 increase with age, and that CD38 was required for age-related NAD decline and mitochondrial dysfunction in mice, acting at least partly through the sirtuin SIRT3. CD38 also turned out to be the main enzyme degrading the NAD precursor NMN in the body.

Human research with NAD+ precursors

NAD+ research has moved into human studies faster than most ageing research, largely through its precursors. In a 2018 randomised, double-blind, placebo-controlled crossover trial published in Nature Communications, Martens, Seals and colleagues at the University of Colorado Boulder found that six weeks of nicotinamide riboside, an NAD+ precursor vitamin, was well tolerated and effectively stimulated NAD+ metabolism in healthy middle-aged and older adults (PMID: 29599478, PMC5876407). The authors highlighted blood pressure and arterial stiffness as areas for future trials.

Our NAD+ research guide covers this area in depth.

Epitalon vs NAD+: The Differences That Matter

With both stories told, the key contrasts become clear.

What they are

Epitalon is a synthetic four-amino-acid peptide, molecular weight about 390. NAD+ is a naturally occurring dinucleotide coenzyme, molecular weight about 663, that is not a peptide at all.

Where they act

Epitalon’s research focuses on the nucleus: telomerase expression, telomere length and gene activity, along with its links to the pineal gland and melatonin rhythms. NAD+’s research focuses on metabolism and mitochondria: energy production, sirtuin signalling and DNA repair enzymes.

How they are thought to work

Epitalon is proposed to act as a signal. Like other short peptides from the same research programme, it has been shown in fluorescence studies to enter cells and reach the nucleus, and the Saint Petersburg group proposes that it interacts with DNA to influence which genes are expressed. NAD+ acts as a substrate: something enzymes directly use and consume. Restoring NAD+ is about replenishing a supply, rather than sending an instruction.

The shape of the evidence

Epitalon’s research comes largely from a single productive research school in Saint Petersburg, spanning cell cultures, lifespan studies in rodents and observational work in older people published in Russian-language journals. NAD+ research comes from dozens of laboratories worldwide and has progressed to randomised controlled trials of its precursors in people. The two bodies of evidence differ in breadth and design, which is useful context for anyone deciding which to build on.

Which One Fits a Research Question?

Search data shows people asking “Epitalon or NAD+?” as if they were rival products. In research terms, they answer different questions.

When Epitalon fits

Epitalon suits research on telomere biology, telomerase regulation, replicative senescence in cell cultures, pineal and circadian biology, and epigenetic effects of short peptides. It is also the natural reference compound for anyone working with other Khavinson bioregulators, such as Pinealon.

When NAD+ fits

NAD+ suits research on cellular energy metabolism, mitochondrial function, sirtuin and PARP biology, DNA repair capacity, and the metabolic side of ageing. It is also relevant to studies of CD38 and the mechanisms behind age-related NAD+ decline.

Why they are sometimes studied together

Because they act on different hallmarks of ageing, the two are complementary rather than competing. Research designs that measure both telomere-related and metabolic endpoints can use each compound to probe its own pathway, and there is an interesting point of overlap: PARPs, which consume NAD+, are also involved in maintaining telomeres. Telomere biology and NAD+ biology are not as separate as they first appear.

The Technical Breakdown: Two Molecules, Two Kinds of Chemistry

This section is for readers who want the molecular detail. The comparison above stands without it.

Telomeres and telomerase

Telomeres are long runs of a repeated six-letter DNA sequence, TTAGGG in humans, at the ends of each chromosome, capped by a protein complex called shelterin. Because the machinery that copies DNA cannot quite reach the very end of a chromosome, a little telomere is lost at each cell division. When telomeres become critically short, cells stop dividing and enter senescence. Telomerase is an enzyme that adds TTAGGG repeats back on. It has two essential components: TERT, the catalytic protein subunit, and TERC, an RNA template. Most adult somatic cells express very little TERT, which is why the 2003 finding of TERT expression in Epitalon-treated fibroblasts attracted attention.

How Epitalon might reach the genome

A 2011 study in Biochemistry (Moscow) used fluorescently labelled Epitalon, Pinealon and Testagen and found all three in the cytoplasm, nucleus and nucleolus of HeLa cells. The same work suggested the peptides interacted with specific DNA sequences and were sensitive to cytosine methylation, a key epigenetic mark. That is the basis of the proposal that Epitalon acts as an epigenetic regulator.

NAD+ and its consumers

NAD+ is made in the body by three main routes: from the amino acid tryptophan, from nicotinic acid, and, most importantly for recycling, from nicotinamide via the salvage pathway. In that pathway, the enzyme NAMPT converts nicotinamide to NMN, which is then converted to NAD+. Sirtuins, PARPs and CD38 all break NAD+ apart, releasing nicotinamide that the salvage pathway can reuse.

NAD+ versus NMN and NR

Searches such as “NAD vs NMN” reflect a common confusion. NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are precursors, molecules the cell converts into NAD+. NAD+ itself is the end product. Much of the human research has used precursors, because they are smaller and have been studied extensively for uptake; research using NAD+ directly addresses the end molecule and its extracellular metabolism, including the role of CD38 and related enzymes in breaking it down.

Oxidised and reduced forms

The “+” in NAD+ refers to the oxidised form, which is ready to accept electrons. After it accepts them, it becomes NADH. The ratio of NAD+ to NADH in a cell is itself an important signal of the cell’s metabolic state.

Quality Matters Differently for Each

These two compounds present very different manufacturing and testing challenges.

Epitalon is a short peptide, so synthesis is relatively straightforward, but short sequences have a particular vulnerability: a deletion impurity in a four-residue chain is not a slightly shorter Epitalon but a completely different tripeptide. And because the research on Epitalon rests on sequence-specific effects, contamination with related short peptides would undermine any result. Accurate identity confirmation by mass spectrometry is essential.

NAD+ is supplied in far larger quantities, typically hundreds of milligrams per vial, and its main quality concern is stability. It can break down into nicotinamide and ADP-ribose, particularly in solution, at higher temperatures or at unfavourable pH, and it is sensitive to light. Purity testing needs to distinguish intact NAD+ from these breakdown products.

How Crown Peptides verifies both

Every batch of Epitalon and NAD+ supplied by Crown Peptides comes with a batch-specific certificate of analysis. HPLC confirms purity by separating the target compound from related substances, and mass spectrometry confirms molecular identity. Lot numbers on certificates match those on vial labels. You can view published certificates on our Lab Reports page and learn to read them with how to read a certificate of analysis.

Handling

Both are supplied as lyophilised powders and should be stored cold, dry and away from light. NAD+ in particular benefits from being kept cold and protected from light once in solution. Our guides to reconstitution, how long peptides last and the peptide calculator cover the practical side, and Bacteriostatic Water is available alongside both.

Related Compounds in Ageing and Cellular Research

Epitalon and NAD+ each have close neighbours in the research catalogue.

Epitalon’s family

Pinealon is Epitalon’s sibling from the same Saint Petersburg programme, a three-amino-acid peptide focused on neurons rather than systemic ageing. The two were tested side by side in a 2024 study of ageing human neurons. Read our Pinealon guide for the full story. For sleep-related pineal research, DSIP is another neighbour.

NAD+’s mitochondrial neighbours

MOTS-c is a peptide encoded in mitochondrial DNA that research has shown may improve metabolic regulation and physical capacity in mice, and SS-31 is a mitochondria-targeted peptide that binds cardiolipin on the inner mitochondrial membrane. Our comparisons NAD+ vs MOTS-c and SS-31 vs MOTS-c set out the differences. 5-Amino-1MQ, which inhibits the NAD+-related enzyme NNMT, and Methylene Blue, studied for its effects on mitochondrial electron transport, round out the group.

Antioxidant and tissue ageing research

Glutathione is the cell’s main antioxidant tripeptide, and GHK-Cu is a copper peptide whose plasma levels decline with age. Both are widely used in ageing-related research.

Browse the full range in our ageing and cellular research peptides category.

Epitalon and NAD+ Questions, Answered

Is Epitalon the same as Epithalon?

Yes. They are two spellings of the same four-amino-acid peptide, Ala-Glu-Asp-Gly. Epithalamin, by contrast, is the original pineal gland extract from which Epitalon was derived.

Is NAD+ a peptide?

No. NAD+ is a coenzyme made of two nucleotides. It is supplied by peptide suppliers because it is widely used in the same research areas.

What is the difference between NAD+ and NMN?

NMN is a precursor that cells convert into NAD+. NAD+ is the active coenzyme itself.

Which has more human research?

NAD+ research, largely through its precursors such as nicotinamide riboside, includes randomised controlled trials in people. Epitalon’s human research is mainly observational and published in Russian-language journals, alongside a substantial body of cell and animal work.

Why does so much Epitalon research come from Saint Petersburg?

Because the compound was designed there, and the Institute of Bioregulation and Gerontology has spent decades building a systematic programme around it and its sibling peptides, working with partner institutes in oncology, cytology and primate research. That concentration is common for compounds developed within a single research tradition, and the collaborations are widening: in a 2024 study led by the Institute of Cytology in Saint Petersburg, for example, Epitalon was tested alongside other short peptides in neurons reprogrammed from elderly donors’ skin cells, one of the most advanced human ageing models available. Replication by more laboratories around the world is the natural next chapter for Epitalon research, and a very exciting one.

Can Epitalon and NAD+ be studied together?

Yes. They act on different hallmarks of ageing, telomere biology and cellular energy metabolism, so they are complementary tools, and research measuring both kinds of endpoint can use each to probe its own pathway.

Two Clocks, One Question

If ageing were a single process, there would be a single answer. Instead, the cell keeps time in several ways at once. One clock is written into the ends of its chromosomes, a few letters shorter at every division. Another runs through its energy supply, in a molecule that slowly becomes scarcer as enzymes such as CD38 consume more of it. Epitalon is a tool for studying the first clock, a tiny peptide from a Cold War research programme that switched on telomerase in cells that had forgotten how. NAD+ is a tool for studying the second, a molecule first found in yeast juice that now sits at the centre of some of the most active research in biology.

Choosing between them is really a matter of choosing which clock you want to study, and the most interesting work increasingly looks at both. Explore Epitalon and NAD+ from Crown Peptides, every batch HPLC and mass spectrometry verified and dispatched from the UK.