Longevity Peptides: NAD+, SS-31, MOTS-c, and SLU-PP-332

Last Updated: April 2026 | v1.0

Longevity peptides are a group of research compounds studied in preclinical mitochondrial, cellular senescence, and metabolic aging models for their capacity to influence bioenergetic signaling, sirtuin activity, and mitochondrial membrane integrity. The category is defined less by a single receptor target than by a shared experimental focus: the biology of the mitochondrion and the regulatory networks that govern cellular energy homeostasis as cells and tissues age. Four compounds appear most frequently in the published literature for this research area — nicotinamide adenine dinucleotide (NAD+), the mitochondrial-targeted peptide SS-31 (Elamipretide), the mitochondrial-derived peptide MOTS-c, and the small-molecule ERR agonist SLU-PP-332. Three of the four are peptides or nucleotide coenzymes; the fourth, SLU-PP-332, is a small molecule studied alongside mitochondrial peptides because it engages the same bioenergetic pathways. This guide explains what longevity peptides are, how each of these four compounds engages its target pathway, what the published preclinical research has reported, and how researchers select among them for different experimental questions. All compounds and information presented are provided for laboratory and research purposes only.

Quick Comparison: NAD+ vs SS-31 vs MOTS-c vs SLU-PP-332

The four compounds in this guide differ substantially in chemical class, mitochondrial target, and the research questions they are most often used to investigate. The table below summarizes the key distinctions.

Attribute	NAD+	SS-31 (Elamipretide)	MOTS-c with DAC	SLU-PP-332
Chemical class	Pyridine nucleotide coenzyme	Synthetic tetrapeptide (D-Arg-dmT-Lys-Phe-NH2)	Mitochondrial-derived 16-amino-acid peptide (DAC-modified)	Small-molecule ERR agonist
Primary target	Sirtuins, PARPs, electron transport chain	Cardiolipin on the inner mitochondrial membrane	AMPK / folate-methionine cycle / metabolic signaling	Estrogen-related receptors (ERRα/β/γ)
Mechanism	Redox coenzyme and sirtuin substrate	Binds cardiolipin, stabilizes cristae, preserves ETC efficiency	mtDNA-encoded peptide signaling; modulates metabolic homeostasis	Agonizes ERR to drive mitochondrial biogenesis and fiber-type switching
Unique aspect	Direct substrate for NAD+-dependent enzymes	Only compound in this category with direct cardiolipin affinity	Encoded within the 12S rRNA region of mitochondrial DNA	Described in published research as an “exercise mimetic”
Peptide or not?	Not a peptide (nucleotide coenzyme)	Peptide (tetrapeptide)	Peptide (16-mer, DAC-modified)	Not a peptide (small molecule)
Available format	NAD+ 500 mg	SS-31 10 mg	MOTS-c with DAC	SLU-PP-332 5 mg

What Are Longevity Peptides?

Longevity peptides — more precisely, longevity research compounds — are a heterogeneous category of molecular tools studied in preclinical models of cellular aging, mitochondrial dysfunction, and bioenergetic decline. The category’s unifying theme is not a shared chemical class but a shared experimental focus: the mitochondrion and the regulatory networks that surround it. The mitochondrial free-radical theory of aging, first proposed by Denham Harman in the 1950s and elaborated in subsequent decades, positioned mitochondrial reactive oxygen species and cumulative mtDNA damage as central drivers of age-associated cellular decline (PubMed: 13332224). While the theory has been refined and in some respects challenged by later work, the mitochondrion remains a dominant focus of cellular aging research, and compounds that engage mitochondrial bioenergetics are heavily represented in the contemporary longevity literature.

Sirtuin biology provides a second organizing principle. Sirtuins are a family of NAD+-dependent deacetylases — seven in mammals (SIRT1-SIRT7) — that regulate metabolism, stress response, DNA repair, and mitochondrial biogenesis through the removal of acetyl groups from target proteins. Because sirtuin activity depends on NAD+ as an obligatory cosubstrate, cellular NAD+ levels directly constrain sirtuin function, and age-associated decline in NAD+ has been characterized as a contributing factor to reduced sirtuin signaling in aged tissues (PubMed: 29599478). This NAD+/sirtuin axis connects three of the four compounds in this guide: NAD+ is the coenzyme itself, MOTS-c influences metabolic signaling that overlaps with AMPK/sirtuin networks, and SLU-PP-332 engages ERR transcription factors that regulate mitochondrial biogenesis in parallel with the sirtuin pathway.

How Does NAD+ Function as a Cellular Coenzyme?

NAD+ (nicotinamide adenine dinucleotide) is a pyridine nucleotide coenzyme present in every living cell and essential for hundreds of enzymatic reactions, most prominently the redox reactions of the mitochondrial electron transport chain (ETC). In its oxidized form (NAD+), the coenzyme accepts electrons from metabolic substrates to become NADH; NADH then donates those electrons to Complex I of the ETC, feeding the proton gradient that drives ATP synthesis. Beyond its role as a redox cofactor, NAD+ is also a direct substrate for three classes of NAD+-consuming enzymes: sirtuins (SIRT1-SIRT7), poly(ADP-ribose) polymerases (PARPs), and cADP-ribose synthases (CD38/CD157). Each of these enzyme classes cleaves NAD+ as part of its catalytic cycle, meaning cellular NAD+ is continuously turned over and must be replenished through de novo synthesis or salvage pathways (PubMed: 26785480).

A central finding in the aging and longevity literature is that cellular NAD+ levels decline with age across multiple tissues in rodent and human studies. This decline has been attributed to several overlapping mechanisms, including increased NAD+ consumption by CD38, reduced expression of salvage-pathway enzymes, and accumulated PARP activity associated with DNA damage. Published reviews by Imai, Guarente, Verdin, and collaborators have characterized this NAD+ decline as a contributing factor to age-associated mitochondrial dysfunction, reduced sirtuin activity, and impaired metabolic homeostasis in rodent models (PubMed: 25724700).

For preclinical research, NAD+ is most often supplied as a lyophilized powder for reconstitution. Peptideware stocks NAD+ as a 500 mg vial format — a high-content vial selected because NAD+ protocols in rodent and cell-culture studies typically require substantially more material per experiment than the peptide compounds in this category. Researchers investigating the NAD+/sirtuin axis, mitochondrial bioenergetics, or metabolic aging models can use the 500 mg format to support extended protocols without frequent reconstitution cycles. NAD+ is not itself a peptide — it is a nucleotide coenzyme — but it is grouped with mitochondrial peptides in this guide because the sirtuin and bioenergetic pathways it regulates are the same pathways that SS-31, MOTS-c, and SLU-PP-332 engage through different molecular mechanisms.

What Makes SS-31 a Mitochondrial-Targeted Peptide?

SS-31, also known as Elamipretide or Bendavia, is a synthetic tetrapeptide with the sequence D-Arg-2′,6′-dimethyl-Tyrosine-Lys-Phe-NH2, developed by Hazel Szeto and Peter Schiller as part of a series of aromatic-cationic peptides designed to localize to the inner mitochondrial membrane (IMM). The defining feature of SS-31 is its selective accumulation at the IMM — reported to reach concentrations several orders of magnitude higher than extracellular levels — where it binds cardiolipin, a phospholipid almost exclusively localized to the IMM and essential for the organization of the electron transport chain and the integrity of mitochondrial cristae (PubMed: 25135651).

Cardiolipin binding is the mechanistic core of SS-31 research. By interacting with cardiolipin, SS-31 has been reported in published studies to preserve cristae structure under conditions of oxidative stress, maintain supercomplex assembly of ETC components, and protect against cardiolipin peroxidation that would otherwise compromise membrane integrity. Birk, Szeto, and colleagues have published extensively on SS-31 in models of mitochondrial dysfunction, ischemia-reperfusion injury, heart failure, and age-associated muscle bioenergetic decline (PubMed: 23928525). A notable feature of SS-31 in the published literature is that its mitochondrial localization is driven by physicochemical properties — the aromatic-cationic structure — rather than by a classical mitochondrial targeting sequence, which distinguishes it from genetically encoded mitochondrial proteins.

In preclinical applications, SS-31 appears in rodent models of cardiac ischemia-reperfusion, skeletal muscle aging, renal ischemic injury, and neurodegeneration models where mitochondrial dysfunction is implicated. The published ranges of administration in these protocols are typically in the low-milligram-per-kilogram range delivered subcutaneously or intraperitoneally in rodents, though exact parameters vary by model. Researchers investigating cardiolipin biology, IMM bioenergetics, or mitochondrial-targeted compound pharmacology can source material as SS-31 (Elamipretide) 10 mg lyophilized powder.

How Is MOTS-c a Mitochondrial-Derived Peptide?

MOTS-c is a 16-amino-acid peptide (MRWQEMGYIFYPRKLR) encoded within the 12S ribosomal RNA region of mitochondrial DNA — a discovery that expanded the understanding of mitochondrial genome function beyond its traditional role in encoding ETC subunits and mitochondrial tRNAs and rRNAs. MOTS-c was identified by Changhan David Lee, Pinchas Cohen, and collaborators, who reported its expression in mitochondria, its secretion into the circulation, and its capacity to regulate metabolic homeostasis in rodent models. The discovery of MOTS-c and related mitochondrial-derived peptides (MDPs) established that mitochondrial DNA encodes bioactive signaling peptides in addition to its canonical role in oxidative phosphorylation (PubMed: 25738459).

Mechanistically, the published MOTS-c literature characterizes the peptide as a metabolic signaling molecule that influences AMPK activation, glucose homeostasis, insulin sensitivity, and the folate-methionine cycle in preclinical models. MOTS-c has been reported to translocate to the nucleus under metabolic stress conditions and to regulate nuclear gene expression programs relevant to metabolic adaptation — a surprising finding for a peptide encoded within the mitochondrial genome and one that has positioned MOTS-c as a mitochondrial-to-nuclear retrograde signal (PubMed: 29983246). Additional published work has examined MOTS-c effects on exercise response, age-associated metabolic decline, and insulin resistance endpoints in rodent models.

Native MOTS-c has a short in-vivo half-life, which limits its use in protocols requiring sustained exposure. Peptideware stocks MOTS-c with DAC — a version of the peptide incorporating a Drug Affinity Complex (DAC) modification that extends plasma half-life by enabling reversible binding to serum albumin. The DAC strategy, familiar from CJC-1295 with DAC in the growth-hormone secretagogue category, applies the same half-life-extension principle to mitochondrial-derived peptide research, allowing protocols with less frequent administration than native MOTS-c would otherwise permit. Researchers investigating mitochondrial-derived peptide signaling, AMPK pathway engagement, or metabolic aging endpoints can use the DAC-modified format in protocols where extended exposure is experimentally appropriate.

What Is SLU-PP-332’s “Exercise Mimetic” Mechanism?

SLU-PP-332 is a small-molecule agonist of the estrogen-related receptor (ERR) family — specifically ERRα, ERRβ, and ERRγ — developed at Saint Louis University and characterized in a series of publications by Thomas Burris, Kristine Griffett, and collaborators, including a 2023/2024 body of work describing its effects on mitochondrial biogenesis and skeletal muscle fiber-type composition (PubMed: 37726544). It is important to state clearly: SLU-PP-332 is a small molecule, not a peptide. It is included in this guide because it is studied alongside mitochondrial peptides in the longevity and bioenergetic research literature, and because the pathway it engages — ERR-driven mitochondrial biogenesis — directly overlaps with the pathways influenced by NAD+, SS-31, and MOTS-c.

The ERRs are orphan nuclear receptors structurally related to the classical estrogen receptors but distinct in ligand binding and downstream gene targets. ERRα in particular is a master regulator of mitochondrial biogenesis, working in concert with transcriptional coactivators such as PGC-1α to drive expression of nuclear-encoded mitochondrial genes, fatty acid oxidation enzymes, and oxidative phosphorylation machinery. SLU-PP-332 research has characterized the compound as a pan-ERR agonist that engages this transcriptional program in skeletal muscle and other metabolically active tissues, with published rodent studies reporting shifts toward more oxidative muscle fiber types, enhanced endurance capacity, and changes in fatty acid metabolism consistent with ERR pathway activation (PubMed: 37797013).

Because these phenotypic effects resemble those produced by endurance exercise, SLU-PP-332 has been described in the published research literature as an “exercise mimetic” — a term that specifically refers to compounds capable of producing exercise-like transcriptional and phenotypic changes in rodent models without requiring the mechanical stimulus of exercise itself. The term is used in the original publications and is cited here in that context. Researchers investigating ERR pharmacology, mitochondrial biogenesis transcriptional programs, or skeletal muscle fiber-type plasticity can source material as SLU-PP-332 5 mg lyophilized powder, with the understanding that the compound is a small molecule being studied alongside mitochondrial peptides rather than a peptide itself.

Mitochondrial Research: What Do Studies Show?

The published preclinical literature on these four compounds spans rodent bioenergetic models, mitochondrial structural and functional analyses, transcriptional profiling, and — for several of the compounds — early translational research programs. The table below summarizes representative findings and their associated research areas.

Compound	Research area	Representative findings
NAD+	Sirtuin biology, mitochondrial bioenergetics	Age-associated decline in tissue NAD+ correlates with reduced sirtuin activity and mitochondrial dysfunction in rodent models; NAD+ replenishment strategies restore aspects of mitochondrial function in preclinical aging studies (PubMed: 25724700)
SS-31	Cardiolipin interaction, cristae integrity	Preserves cristae structure and ETC supercomplex assembly under oxidative stress; studied in rodent models of cardiac ischemia-reperfusion, renal injury, and age-associated muscle bioenergetic decline (PubMed: 23928525)
MOTS-c	Mitochondrial-derived peptide signaling, AMPK	Modulates AMPK activation, insulin sensitivity, and folate-methionine cycle metabolism in rodent models; translocates to the nucleus under metabolic stress to regulate nuclear gene expression (PubMed: 29983246)
SLU-PP-332	ERR agonism, mitochondrial biogenesis	Pan-ERR agonist reported to drive mitochondrial biogenesis and oxidative fiber-type shifts in rodent skeletal muscle; described in published research as an exercise mimetic (PubMed: 37726544)

Across all four compounds, the published literature should be interpreted as preclinical mechanistic data. Most findings are drawn from rodent models and cell-culture systems, and translation to other species or settings requires careful consideration of differences in mitochondrial biology, metabolic rate, and receptor distribution. Sample sizes and experimental designs vary substantially across studies, and the degree to which any individual finding has been independently replicated should be confirmed by direct literature review. For SLU-PP-332 in particular, the preclinical track record is comparatively recent — the foundational Saint Louis University publications date from 2023 forward — and the body of independent replication work is still developing. Researchers designing protocols involving any of these compounds should ground their study design in the primary literature and institutional review processes appropriate to their research model.

Frequently Asked Questions

Where can researchers source verified NAD+ and SS-31?

Peptideware supplies all four compounds covered in this guide as lyophilized powder with independent third-party Certificates of Analysis reporting HPLC purity and mass spectrometry confirmation for every batch. The four compounds are available as NAD+ 500 mg, SS-31 (Elamipretide) 10 mg, MOTS-c with DAC, and SLU-PP-332 5 mg. Researchers can review the analytical documentation for each lot on the Peptideware lab results page before placing a research order. All compounds are sold for laboratory and research purposes only.

What dosages are referenced in published mitochondrial peptide research?

Published SS-31 rodent studies have referenced dosages in the low-milligram-per-kilogram range, commonly 1-5 mg/kg delivered subcutaneously or intraperitoneally in ischemia-reperfusion and mitochondrial dysfunction models (PubMed: 23928525). MOTS-c rodent studies have referenced dosages in the low-milligram-per-kilogram range delivered intraperitoneally in metabolic and insulin-sensitivity protocols (PubMed: 25738459). NAD+ preclinical protocols vary widely depending on the delivery route, and SLU-PP-332 published rodent protocols have referenced milligram-per-kilogram oral or intraperitoneal administration in the ERR agonism and mitochondrial biogenesis studies. These figures describe dosages reported in published preclinical animal protocols and are provided as literature reference only — researchers should consult the primary literature and their institutional protocols when designing any study.

How does MOTS-c with DAC differ from native MOTS-c?

Native MOTS-c has a short circulating half-life, which limits the duration of biological exposure in protocols using a single administration. MOTS-c with DAC incorporates a Drug Affinity Complex modification that enables reversible binding to serum albumin, substantially extending plasma half-life. The DAC modification is the same half-life-extension strategy applied in CJC-1295 with DAC and functions by attaching a chemical linker that covalently binds to a free cysteine residue on serum albumin after injection. The biological signaling of the peptide is preserved, but the pharmacokinetics allow for protocols with less frequent administration than native MOTS-c would otherwise permit. Researchers choosing between native and DAC-modified versions should base the decision on the experimental question — studies investigating acute signaling events may prefer native peptide, while studies requiring sustained exposure may benefit from the DAC format.

Is SLU-PP-332 a peptide?

No. SLU-PP-332 is a small-molecule agonist of the estrogen-related receptor (ERR) family — specifically a pan-ERR agonist engaging ERRα, ERRβ, and ERRγ. It is a synthetic organic compound, not an amino acid chain, and it does not share the chemical class of the peptides elsewhere in this guide. SLU-PP-332 is grouped with mitochondrial peptides in the longevity research context because the pathway it engages — ERR-driven mitochondrial biogenesis — overlaps directly with the bioenergetic pathways influenced by NAD+, SS-31, and MOTS-c. Researchers should categorize SLU-PP-332 as a research compound rather than a research peptide when describing it in protocols or literature reviews. This distinction matters for accurate scientific communication and for appropriate assignment of the compound within receptor pharmacology literature.

How are these compounds reconstituted for research use?

All four compounds are supplied as lyophilized powder in sealed glass vials and are reconstituted by slowly injecting bacteriostatic water along the inside wall of the vial, allowing 2-3 minutes for dissolution, then gently rolling the vial. The volume of bacteriostatic water determines the final concentration — for example, 5 mL added to a 500 mg NAD+ vial yields 100 mg/mL, while 2 mL added to a 10 mg SS-31 vial yields 5 mg/mL. For full procedural detail, see the Peptide Reconstitution 101 walkthrough. Researchers should select reconstitution volumes appropriate to their protocol concentration and expected duration of use.

How should these compounds be stored?

All four compounds are stored as lyophilized powder at -20 °C in a freezer, where they remain stable for 12-24 months in sealed vials. After reconstitution in bacteriostatic water, solutions are stored at 2-8 °C (standard refrigerator temperature) and are typically used within 21-28 days. Repeated freeze-thaw cycles of reconstituted solutions should be avoided, as should exposure to direct sunlight or temperatures above 25 °C. NAD+ in solution is particularly sensitive to pH and light, and published literature notes that reconstituted NAD+ degrades more rapidly under alkaline or warm conditions than many peptides in storage; researchers should plan protocols accordingly.

How do these four compounds compare mechanistically?

The four compounds engage different molecular targets but converge on the same cellular endpoint: mitochondrial bioenergetic function. NAD+ is a coenzyme and direct substrate for sirtuins and other NAD+-consuming enzymes, influencing mitochondrial function through the sirtuin/PGC-1α axis and through its role in the ETC. SS-31 acts at the inner mitochondrial membrane itself, binding cardiolipin and preserving cristae architecture under oxidative stress. MOTS-c is a mitochondrial-derived peptide that signals metabolically through AMPK and regulates nuclear gene expression under stress conditions. SLU-PP-332 is a small-molecule ERR agonist that drives the transcriptional program of mitochondrial biogenesis. Because the four compounds engage non-overlapping primary targets, they are studied as complementary rather than substitutable research tools, and published work occasionally combines them within a single experimental framework to dissect contributions from different levels of the bioenergetic hierarchy.

For research purposes only. All products and information are provided for laboratory and research purposes only. These compounds are not approved for human consumption and are not drugs, supplements, or cosmetics. Researchers are responsible for compliance with all applicable laws and for appropriate laboratory handling.