Sirtuin-Activating Peptides
Overview
Sirtuin-activating peptides represent a class of investigational compounds designed to enhance the enzymatic activity of sirtuins, a family of NAD-dependent deacetylases implicated in longevity and metabolic regulation. These peptides aim to mimic or potentiate the effects of caloric restriction by modulating histone deacetylation, mitochondrial biogenesis, and stress resistance pathways. While small molecule sirtuin activators such as resveratrol analogues have received more research attention, peptide-based approaches remain in early discovery phases. The therapeutic rationale centers on reproducing the lifespan-extending effects of sirtuin overexpression observed in lower organisms.
Key Research Findings
Most evidence for sirtuin activation and longevity derives from studies using genetic manipulation or small molecule activators in yeast, worms, and mice rather than peptide therapeutics. Peptide-based sirtuin modulators have been characterized in vitro and in preliminary rodent studies, but no clinical trials have evaluated safety or efficacy in humans. The translation of sirtuin biology to human aging interventions remains an active area of investigation without conclusive clinical proof of concept.
Subcutaneous injection
Research Phase
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Epithalon (Epitalon)
Research PhaseA synthetic tetrapeptide (Ala-Glu-Asp-Gly) based on the natural epithalamin peptide produced by the pineal gland. Epithalon activates telomerase, the enzyme responsible for maintaining telomere length, thereby potentially extending cellular replicative capacity. It also stimulates melatonin production and modulates neuroendocrine system function associated with aging.
MOTS-c
Research PhaseA mitochondrial-derived peptide encoded by the 12S rRNA gene of mitochondrial DNA. MOTS-c is a 16-amino acid peptide that acts as an exercise mimetic by activating AMPK and regulating metabolic homeostasis. It translocates to the nucleus under metabolic stress to regulate nuclear gene expression related to glucose metabolism and cellular stress responses.
Humanin
Research PhaseA 24-amino acid mitochondrial-derived peptide encoded within the 16S rRNA region of mitochondrial DNA. Humanin exerts cytoprotective and neuroprotective effects by interacting with IGFBP-3, BAX, and the FPRL-1 receptor. It inhibits apoptosis through suppression of the intrinsic mitochondrial death pathway and reduces amyloid-beta-induced neurotoxicity.
NAD+ Precursors (NMN)
In Clinical TrialsNicotinamide mononucleotide (NMN) is a direct biosynthetic precursor to nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for cellular metabolism, DNA repair (via sirtuins and PARPs), and circadian rhythm regulation. NAD+ levels decline with age, and NMN supplementation restores tissue NAD+ levels, activating SIRT1-mediated pathways that regulate mitochondrial biogenesis and oxidative stress resistance.