Best Peptides for Longevity Research: Epitalon, NAD+, MOTS-c, SS-31 and More

Ageing used to be treated as a single, unstoppable slide. Modern biology sees it very differently: as a set of distinct processes, each of which can be measured, studied and, in the laboratory at least, nudged. Chromosomes lose their protective caps. Cells run short of a vital energy molecule. Mitochondria falter. The body’s antioxidant defences thin out. Old cells stop dividing and linger. Each of those processes now has research compounds built around it, and several of them are peptides.

This guide explains the main compounds used in longevity and ageing research in plain English, organised by the ageing process each one targets, with the key studies named. It is designed to help you match the right compound to the right question. Every compound mentioned is supplied by Crown Peptides for laboratory research use only.

Ageing as a Set of Processes, Not a Single Clock

The hallmarks of ageing

In 2013, Carlos López-Otín and colleagues published an influential paper in the journal Cell that grouped the biology of ageing into a set of “hallmarks”, distinct but interconnected processes that together drive the changes we recognise as ageing (PMID: 23746838). The list, since expanded, includes telomere attrition, epigenetic changes, mitochondrial dysfunction, deregulated nutrient sensing, cellular senescence, loss of protein maintenance, stem cell exhaustion and altered communication between cells.

Why that framework is useful

The hallmarks turn a vague question, “what slows ageing?”, into specific, testable ones. Which compound acts on telomeres? Which on mitochondria? Which on the cell’s energy sensors? That is exactly how researchers choose longevity compounds, and it is how this guide is organised.

Lifespan vs Healthspan

Longevity research distinguishes between two goals. Lifespan is how long an organism lives. Healthspan is how long it lives in good health, free of disease and disability. Many researchers now consider healthspan the more important target: adding healthy years rather than simply more years. That shift matters when reading studies. The 2021 MOTS-c study, for example, measured physical capacity in old mice, a healthspan measure, while the Epitalon lifetime study measured survival, a lifespan measure. Both kinds of evidence are valuable, but they answer different questions.

How Ageing Is Measured in the Laboratory

Because ageing takes years, researchers rely on biomarkers that change with age and can be measured more quickly.

Telomere length

Measured in cells or tissues, telomere length is one of the best-known markers of cellular ageing, along with the activity of telomerase.

Epigenetic clocks

In 2013, Steve Horvath at UCLA developed an “epigenetic clock” that estimates biological age from chemical tags, called methylation marks, on DNA. Epigenetic clocks are now widely used to test whether an intervention changes biological age, independent of calendar age.

NAD+ levels

NAD+ and related molecules can be measured in blood and tissues, and their decline with age makes them a natural biomarker for metabolic ageing studies.

Senescence markers

Senescent cells, old cells that have stopped dividing but refuse to die, can be detected with markers such as senescence-associated beta-galactosidase and the proteins p16 and p21. They release inflammatory signals that are thought to drive tissue ageing.

Functional measures

In animals, researchers measure grip strength, endurance, coordination and frailty indices. In people, walking speed, grip strength and the ability to perform daily activities are among the most informative measures of healthy ageing.

The Model Organisms of Ageing Research

Much of what we know about ageing comes from surprisingly simple organisms. Yeast revealed the role of sirtuins and NAD+. The tiny roundworm C. elegans, which lives about three weeks, showed that single gene changes could double lifespan. Fruit flies, with lifespans of a couple of months, let researchers test interventions quickly. Mice, living two to three years, are the main mammalian model and the standard test before any human study. Each model has strengths, and findings are most convincing when they hold across several.

The Benchmarks: Calorie Restriction and Exercise

Two interventions reliably extend healthspan across many species: calorie restriction and exercise. They set the standard that longevity compounds are compared against, and many compounds are studied precisely because they seem to mimic one or the other. Calorie restriction raises NAD+ and activates sirtuins and AMPK; exercise activates AMPK and, as the 2021 study found, raises MOTS-c. Seen this way, NAD+ and MOTS-c research is partly an attempt to understand how the body’s response to less food and more movement keeps it young.

Telomeres: Epitalon

The protective caps

Telomeres are long runs of repeated DNA at the ends of every chromosome. Each time a cell divides, a little telomere is lost. When telomeres become critically short, cells stop dividing. An enzyme called telomerase can rebuild them, but most adult cells make very little of it.

What the research shows

Epitalon is a four-amino-acid peptide, Ala-Glu-Asp-Gly, developed at the Saint Petersburg Institute of Bioregulation and Gerontology from a pineal gland extract. In 2003, Khavinson and colleagues reported that adding Epitalon to human fetal fibroblasts, which normally lack active telomerase, induced telomerase expression and activity and lengthened telomeres (PMID: 12937682). A follow-up study found treated cells divided ten times beyond the point at which control cells stopped (PMID: 15455129).

In a lifetime study in female mice published in Biogerontology in 2003, Epitalon did not change mean lifespan, but increased the lifespan of the longest-lived 10% of animals by 13.3% and maximum lifespan by 12.3%, reduced chromosome aberrations in bone marrow cells and lowered leukaemia incidence six-fold (PMID: 14501183).

Best suited to

Research on telomere biology, telomerase regulation, replicative senescence and pineal and circadian ageing. See our Epitalon guide.

Cellular Energy: NAD+

The molecule every cell runs on

NAD+, nicotinamide adenine dinucleotide, is a coenzyme found in every living cell. It carries electrons in energy production and is consumed as fuel by sirtuins, enzymes linked to ageing, and by PARPs, enzymes that repair DNA.

What the research shows

The link between NAD+ and ageing began in 2000, when Imai, Guarente and colleagues showed in Nature that the yeast longevity protein Sir2 is an NAD-dependent enzyme, connecting metabolism directly to lifespan (PMID: 10693811). A 2014 review by Imai and Guarente in Trends in Cell Biology described NAD+ decline with age as a potential “Achilles’ heel” and summarised research in which restoring NAD+ improved age-associated defects in animal models (PMID: 24786309, PMC4112140). A 2016 Mayo Clinic study in Cell Metabolism identified the enzyme CD38 as a key driver of age-related NAD+ decline (PMID: 27304511, PMC4911708). And a 2018 randomised trial in Nature Communications found that the NAD+ precursor nicotinamide riboside was well tolerated and raised NAD+ metabolism in healthy middle-aged and older adults (PMID: 29599478, PMC5876407).

Best suited to

Research on cellular energy metabolism, sirtuin and PARP biology, DNA repair and the metabolic side of ageing. See our NAD+ guide and Epitalon vs NAD+.

Mitochondrial Signalling: MOTS-c

A message from the mitochondria

MOTS-c is a 16-amino-acid peptide encoded not in the cell’s main DNA but in the small genome inside mitochondria. It was discovered in 2015 by Changhan Lee, Pinchas Cohen and colleagues, who found in Cell Metabolism that it activated AMPK, the cell’s energy sensor, and prevented both age-dependent and diet-induced insulin resistance in mice (PMID: 25738459, PMC4350682).

What the research shows

In 2021, Reynolds, Lee and colleagues reported in Nature Communications that MOTS-c enhanced physical performance in young, middle-aged and old mice, and that intermittent treatment started very late in life increased physical capacity and healthspan (PMID: 33473109, PMC7817689). They also found that exercise raises natural MOTS-c levels in human muscle and blood.

Best suited to

Research on metabolic ageing, physical capacity, AMPK signalling and communication between mitochondria and the nucleus. See our MOTS-c guide.

Mitochondrial Structure: SS-31

Protecting the power station’s inner wall

SS-31 is a four-amino-acid peptide developed by Hazel Szeto and Peter Schiller. It concentrates on the inner mitochondrial membrane, where it binds cardiolipin, a lipid unique to that membrane and essential for the machinery that produces energy. Cardiolipin damage is a feature of ageing mitochondria.

From research to medicine

SS-31 is one of the few compounds in a research catalogue with a direct link to an approved medicine. On 19 September 2025, the US Food and Drug Administration granted accelerated approval to elamipretide, SS-31’s clinical name, as the first treatment for Barth syndrome, a rare inherited mitochondrial disease, based on improvements in muscle strength.

Best suited to

Research on mitochondrial membrane integrity, bioenergetics and mitochondrial ageing. See SS-31 vs MOTS-c.

Antioxidant Defences: Glutathione

Glutathione, a three-amino-acid peptide, is the cell’s master antioxidant. Several studies have reported lower glutathione in older adults. In a 2023 randomised, placebo-controlled trial in the Journal of Gerontology, Kumar, Sekhar and colleagues at Baylor College of Medicine found that supplementing glycine and N-acetylcysteine, the building blocks of glutathione, for 16 weeks improved glutathione deficiency, oxidative stress, mitochondrial function, inflammation, markers of ageing and physical function in older adults (PMID: 35975308, PMC9879756).

Best suited to research on oxidative stress, redox balance and the antioxidant side of ageing. See why glutathione is known as the master antioxidant.

Tissue Ageing: GHK-Cu

GHK-Cu is a copper-binding tripeptide found in human plasma, first identified in 1973 by Loren Pickart because young plasma made older liver cells behave more youthfully. Plasma GHK declines with age. A 2018 review by Pickart and Margolina described research indicating GHK may stimulate collagen and blood vessel growth, support fibroblasts and influence a very large number of genes linked to repair and protection (PMID: 29986520, PMC6073405).

Best suited to research on skin and connective tissue ageing and on gene expression changes with age. See our GHK-Cu guide.

Neuronal Ageing: Pinealon

Pinealon, Epitalon’s three-amino-acid sibling, is studied for protecting neurons. In a 2024 study, it promoted dendrite growth and reduced oxidative DNA damage in neurons made directly from the skin cells of elderly donors, one of the most advanced models of human neuronal ageing available (PMID: 39518916, PMC11546785). Best suited to research on brain ageing and epigenetic regulation. See our Pinealon guide.

Muscle Ageing: 5-Amino-1MQ

5-Amino-1MQ is a small molecule that inhibits NNMT, an enzyme that drains both NAD+ precursors and methyl groups. In a 2019 study in Biochemical Pharmacology, an NNMT inhibitor increased muscle stem cell activity after injury in 24-month-old mice, nearly doubled the size of regenerating muscle fibres and increased peak muscle strength by about 70% (PMID: 30753815, PMC6469996). Best suited to research on muscle ageing and the NAD+ supply. See our 5-Amino-1MQ guide.

Why the Pineal Gland Keeps Appearing

Two of the compounds in this guide, Epitalon and Pinealon, come from research on the pineal gland, a tiny structure deep in the brain that produces melatonin and helps set the body’s daily rhythms. The Saint Petersburg researchers who developed them were interested in the pineal gland because its melatonin output declines with age and because disrupted daily rhythms are associated with many age-related changes. In a 2004 study in Neuroendocrinology Letters, Epitalon restored the night-time melatonin rise and the normal daily rhythm of cortisol in old monkeys (PMID: 14743609). That link between the body clock and ageing is one of the more distinctive threads in longevity research, and one where peptides have played a central part.

Growth Hormone and Ageing

Growth hormone secretion declines steadily through adult life, a change sometimes called the somatopause. Researchers interested in how that decline contributes to changes in muscle, fat and even cognition study compounds that stimulate the body’s own growth hormone release, such as Tesamorelin and Ipamorelin. It is a complex area, because lower growth hormone signalling has also been linked to longer lifespan in some animal models, which is exactly why it remains an active research question rather than a settled answer.

Matching the Compound to the Hallmark

Here is the short version of this guide, organised by the specific ageing process each compound targets.

• Telomere attrition: Epitalon.
• Declining NAD+ and nutrient sensing: NAD+, with 5-Amino-1MQ for the NNMT angle.
• Mitochondrial signalling: MOTS-c.
• Mitochondrial structure: SS-31.
• Oxidative stress: Glutathione.
• Tissue and skin ageing: GHK-Cu.
• Neuronal ageing and epigenetics: Pinealon.
• Muscle stem cell exhaustion: 5-Amino-1MQ.

Why Longevity Researchers Combine Tools

Because the hallmarks of ageing are interconnected, many research designs deliberately target more than one. Telomere biology and NAD+ biology overlap, for example, because PARP enzymes that consume NAD+ are also involved in maintaining telomeres. Mitochondrial dysfunction increases oxidative stress, which in turn damages telomeres. Studying compounds side by side, and in combination, lets researchers explore those links.

A sensible design

The clearest approach compares each compound alone and together, measuring endpoints for each hallmark involved, for example telomere length and telomerase activity alongside NAD+ levels, mitochondrial function and markers of oxidative damage. Matching each measurement to a hallmark keeps results interpretable.

Designing a Longevity Study

Start with the hallmark

The clearest longevity studies begin by naming the hallmark they want to test, then choosing a compound and a readout that match it. A study of telomere biology needs telomere length and telomerase activity; a study of NAD+ needs NAD+ levels and sirtuin activity; a study of mitochondria needs measures of respiration and reactive oxygen species.

Choose the right age

Because many age-related changes only appear in older animals, the age at which treatment starts matters enormously. The 2021 MOTS-c study deliberately started treatment in very old mice, while the Epitalon lifetime study began in middle age. Starting too early or too late can hide real effects.

Include both sexes

Ageing and the response to interventions often differ between males and females. Including both, and analysing them separately, has become standard good practice.

Measure function, not just molecules

A change in a biomarker is most meaningful when it comes with a change in function, such as strength, endurance or cognitive performance. The strongest studies measure both.

Where the Human Evidence Stands

It is important to be clear about the kind of evidence behind each compound. NAD+ precursors have been tested in randomised human trials, such as the 2018 nicotinamide riboside study. Glutathione precursors have been tested in a randomised trial in older adults. SS-31 has reached approval as a medicine for a rare mitochondrial disease. MOTS-c has human observational data, including its rise with exercise. Epitalon, Pinealon and GHK-Cu have been studied mainly in cells and animals, with some clinical research reported from Russia for Epitalon. Each type of evidence has its place, and the articles on this site always name the kind of study behind a finding.

Common Pitfalls in Ageing Research

Longevity studies are uniquely vulnerable to a few problems. Small differences in diet, housing or infections can affect lifespan more than the compound being tested. Animals that eat less for any reason may live longer, so food intake must be tracked. Short studies may miss late effects, and very long ones are vulnerable to drift in the quality of the materials used. Careful controls, consistent verified materials and clear reporting of all these factors are what separate convincing studies from misleading ones.

The Technical Breakdown: How the Hallmarks Connect

This section goes deeper for readers who want the biology.

The NAD+ and sirtuin axis

Sirtuins remove acetyl groups from proteins, including histones, using NAD+ as fuel. SIRT1 in the nucleus regulates gene activity and metabolism; SIRT3 in the mitochondria regulates energy production. When NAD+ falls, sirtuin activity falls with it. The 2016 CD38 study showed that CD38 drives age-related NAD+ decline partly through reduced SIRT3 activity, directly linking the energy hallmark to the mitochondrial hallmark.

AMPK: the energy sensor

AMPK is activated when a cell’s energy runs low. It switches on energy-generating processes and switches off energy-consuming ones, and it is one of the main routes through which exercise and calorie restriction affect metabolism. MOTS-c’s activation of AMPK is why it is often described as an exercise mimetic in research.

Cardiolipin and the electron transport chain

The machinery that produces ATP sits in the inner mitochondrial membrane, arranged into supercomplexes held together partly by cardiolipin. When cardiolipin is oxidised, the machinery becomes less efficient and leaks more reactive oxygen species. SS-31’s binding to cardiolipin is proposed to stabilise that arrangement.

Telomerase and TERT

Telomerase has a protein component, TERT, and an RNA template, TERC. Most adult cells express very little TERT, which is why the 2003 finding of TERT expression in Epitalon-treated fibroblasts attracted so much interest.

Cellular Senescence: The Emerging Frontier

One of the fastest-growing areas of ageing research concerns senescent cells. These cells accumulate with age and secrete a mix of inflammatory molecules known as the senescence-associated secretory phenotype, which can damage surrounding tissue. Research in mice has shown that clearing senescent cells can improve several age-related conditions, and a class of compounds called senolytics has been developed to do exactly that. Several of the compounds in this guide touch this area indirectly: Epitalon through replicative senescence, NAD+ through the metabolic changes in senescent cells, and glutathione through the oxidative stress that can trigger senescence. It is an area where combining tools is particularly promising.

Why Compound Quality Matters for Long Studies

Longevity studies are often long, sometimes lasting the entire lifespan of the animals involved, and they measure subtle changes. That makes consistent, verified material essential. A compound that varies between batches, or degrades in storage, can introduce more variation than the effect being measured.

Every compound supplied by Crown Peptides comes with a batch-specific certificate of analysis showing HPLC purity and mass spectrometry identity, with lot numbers matching vial labels. Published certificates are on our Lab Reports page. Our guides to peptide testing, how long peptides last and peptide reconstitution cover the practical side, and Bacteriostatic Water is available alongside.

Related Compounds and Where to Go Next

Browse the full ageing and cellular research peptides category. For related reading, see NAD+ vs MOTS-c, GHK-Cu vs Glutathione and our brain research guide. L-Carnitine and Methylene Blue round out the mitochondrial toolkit.

Longevity Research Questions, Answered

Which peptide is most studied for longevity?

Epitalon has the longest-running peptide research programme specifically focused on ageing, while NAD+ and its precursors have the broadest international research base and have progressed to controlled human trials.

Is NAD+ a peptide?

No. NAD+ is a coenzyme made of two nucleotides, supplied alongside peptides because it is used in the same research areas.

What are the hallmarks of ageing?

A framework, first published in Cell in 2013, that groups the biology of ageing into distinct processes such as telomere attrition, mitochondrial dysfunction, cellular senescence and loss of stem cell function.

Has any longevity-related peptide become a medicine?

SS-31, as elamipretide, received accelerated US approval in September 2025 for Barth syndrome, a mitochondrial disease. It is approved for that specific condition rather than for ageing.

Can longevity compounds be combined in research?

Yes, and because the hallmarks of ageing are interconnected, combination designs are common. The clearest approach compares each compound alone and together, with a readout matched to each hallmark involved.

Why do so many longevity compounds target mitochondria?

Because mitochondrial dysfunction is one of the central hallmarks of ageing and is linked to several others, including oxidative stress, declining NAD+ and inflammation. Improving mitochondrial function is therefore one of the most studied routes into healthy ageing research.

Is there a single best peptide for longevity research?

No. Each compound in this guide targets a different hallmark of ageing, so the best choice depends on the process being studied. Telomere research points to Epitalon, energy metabolism to NAD+, mitochondrial signalling to MOTS-c, mitochondrial structure to SS-31 and oxidative stress to glutathione. Many studies deliberately combine several to explore how the hallmarks interact.

What is an epigenetic clock?

A method that estimates biological age from chemical methylation marks on DNA. It is widely used in longevity research to test whether an intervention changes the pace of biological ageing.

What is the difference between lifespan and healthspan?

Lifespan is how long an organism lives; healthspan is how long it lives in good health. Many longevity researchers now focus on extending healthspan.

Are these compounds legal in the UK?

None of the compounds in this guide is a controlled drug in the UK. See are peptides legal in the UK.

One Process at a Time

The most exciting shift in ageing science is the move from asking whether ageing can be understood to asking which part of it to study next. Chromosome caps, cellular energy, mitochondrial messages and membranes, antioxidant defences, tissue repair signals, neuronal genes and muscle stem cells each now have compounds that let researchers probe them precisely. The best longevity compound is simply the one that matches the hallmark you most want to understand, and the most powerful studies often bring several of them together in one carefully designed experiment.

Explore the Crown Peptides ageing and cellular research range, every batch HPLC and mass spectrometry verified and dispatched from the UK.