Anti-Aging Peptides: NAD+, SS-31 and Glutathione in Research

EXOMA Scientific Team · Publicado el 13 de abril de 2026 · Actualizado el 17 de agosto de 2026

Scientific analysis of the most researched anti-aging peptides and molecules: NAD+, SS-31 (Elamipretide) y Glutathione. Mecanismos mitocondriales y evidencia.

The Science of Cellular Aging

Biological aging is characterized by the progressive accumulation of cellular damage, mitochondrial dysfunction and loss of regenerative capacity. Three molecules have emerged as main therapeutic targets in anti-aging research: NAD+, SS-31 y Glutathione.

NAD+ (Nicotinamide Adenine Dinucleotide)

Biological Role

NAD+ is an essential coenzyme present in all living cells, involved in more than 500 enzymatic reactions. Its main functions include:

• Energy metabolism: Essential cofactor in the mitochondrial electron transport chain
• DNA repair: Substrate of PARP enzymes (Poly ADP-Ribose Polymerase)
• Epigenetic regulation: Substrate of the sirtuins (SIRT1-7)
• Cell signaling: Precursor of signaling molecules such as cADPR

Decline with Age

NAD+ levels decrease significantly with age:

• 50% reduction between ages 40 and 60 in liver tissue
• Direct correlation with reduced sirtuin activity
• Association with progressive mitochondrial dysfunction
• Contribution to the cellular senescence phenotype

Mechanism of Action

NAD+ supplementation aims to restore cellular levels in order to:

1. Reactivate the sirtuins, especially SIRT1 and SIRT3
2. Mejorar la eficiencia de la fosforilación oxidativa
3. Potenciar la capacidad de reparación del ADN
4. Modular la respuesta inflamatoria (inflammaging)

Scientific Evidence

Studies published in Cell Metabolism y Nature Aging have shown that the restoration of NAD+ in murine models results in:

• Improvement of muscle mitochondrial function
• Reduction of systemic inflammation markers
• Increased resistance to oxidative stress
• Improvement in insulin sensitivity

SS-31 (Elamipretide / Bendavia)

Unique Mechanism

SS-31 is a tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) with exceptional properties:

• Mitochondrial localization: It selectively concentrates in the inner mitochondrial membrane
• Interaction with cardiolipin: Binds to this phospholipid essential for the structure of the respiratory complexes
• Optimization of the respiratory chain: Stabilizes the curvature of the mitochondrial cristae

Mechanisms of Action

1. Stabilization of cardiolipin: Previene la peroxidación de este fosfolípido crítico
2. Optimization of complex IV: Mejora la eficiencia del citocromo c oxidasa
3. Reduction of ROS: Disminuye la producción de especies reactivas de oxígeno en el sitio de generación
4. Protection of mitochondrial permeability: Prevents the opening of the transition pore

Research Applications

SS-31 has been investigated in clinical trials for:

• Heart failure (EMBRACE study): Improvement in ventricular function
• Mitochondrial myopathy (MMPOWER study): Improvement in exercise capacity
• Barth Syndrome: Restoration of cardiolipin levels
• Acute kidney injury: Protection of tubular mitochondrial function

Pharmacological Advantages

• Penetrates cell membranes without the need for transporters
• It accumulates 1000-5000x in mitochondria vs. cytoplasm
• Does not require membrane potential for its uptake
• Effective at nanomolar concentrations

Glutathione (GSH)

The Master Antioxidant

Glutathione (γ-glutamyl-cysteinyl-glycine) is the most abundant intracellular antioxidant in the body:

• Intracellular concentration: 1-10 mM (the most concentrated antioxidant)
• Present in all cells: With higher concentration in liver, lung, and kidney
• Redox cycle: Alternates between reduced (GSH) and oxidized (GSSG) form

Biological Functions

1. ROS neutralization: Sustrato de la glutathione peroxidasa (GPx)
2. Hepatic detoxification: Conjugación con xenobióticos vía glutathione-S-transferasa
3. Recycling of vitamins C and E: Regenera otros antioxidantes
4. Immune regulation: Modula la activación de linfocitos T y NK
5. DNA protection: Prevents oxidative damage to genetic material

Decline with Age

Glutathione levels decrease with aging:

• Reduction of 10-15% per decade after age 45
• Higher GSSG/GSH ratio (oxidative stress)
• Reduction of the activity of γ-glutamylcysteine synthetase

Research Forms

• Reduced glutathione (GSH): Active form, limited oral bioavailability
• Liposomal glutathione: Encapsulation for better absorption
• N-Acetylcysteine (NAC): Precursor that increases endogenous synthesis
• Injectable glutathione: Greater bioavailability for research

Synergies between NAD+, SS-31, and Glutathione

These three compounds act on complementary pathways:

The theoretical combination offers protection at multiple levels:

• NAD+ improves metabolic efficiency
• SS-31 protects the energy production machinery
• Glutathione neutralizes oxidative byproducts

Research Perspectives

Current research focuses on:

• Optimized combinations of these compounds
• Aging biomarkers to measure efficacy
• Dosing protocols in preclinical models
• Clinical translation of findings in animal models

Conclusion

NAD+, SS-31 and Glutathione represent three pillars of anti-aging research at the molecular level. Each addresses complementary aspects of age-associated cellular dysfunction, and their combined study promises significant advances in the understanding and modulation of the aging process.

At Exoma Peptides we carry these three compounds in research grade with certified purity.

References

Material for research use only. Verified primary sources supporting the scientific claims of this article:

1. Mills KF, Yoshida S, Stein LR, et al. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 2016;24(6):795-806. doi:10.1016/j.cmet.2016.09.013. PMID 28068222. (animal)
2. Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. doi:10.1126/science.abe9985. PMID 33888596. (humano)
3. Birk AV, Liu S, Soong Y, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. 2013;24(8):1250-1261. doi:10.1681/ASN.2012121216. PMID 23813215. (in vitro / animal)
4. Sekhar RV, Patel SG, Guthikonda AP, et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr. 2011;94(3):847-853. doi:10.3945/ajcn.110.003483. PMID 21795440. (humano)

Products available at EXOMA

• SS-31