Humanin vs NAD+

Mitochondria-derived peptide; binds gp130 receptor, activates STAT3/JAK pathway; inhibits BAX-mediated apoptosis; improves insulin sensitivity

Humanin is a mitochondrially encoded 21-amino-acid peptide originally identified through its capacity to suppress neuronal apoptosis induced by familial Alzheimer's disease gene products, now recognized as a founding member of the class of mitochondrial-derived peptides (MDPs) with broad cytoprotective actions in neurons, cardiomyocytes, and other metabolically stressed cell types. Humanin exerts its cytoprotective effects through multiple mechanisms: extracellularly, it binds insulin-like growth factor-binding protein 3 (IGFBP-3) to regulate IGFBP-3's interaction with nuclear import machinery and modulate its proapoptotic signaling; intracellularly, it inhibits c-Jun NH2-terminal kinase (JNK) activation through SH3-binding protein 5 to suppress stress-induced apoptotic cascades. PNAS research established that humanin interacts with IGFBP-3 to regulate cell survival and apoptosis, characterizing a molecular basis for its anti-apoptotic activity, and subsequent work identified JNK inhibition as an additional neuroprotective mechanism in humanin-treated neuronal preparations. Humanin is a research compound with no regulatory approval in any jurisdiction; published evidence is predominantly from in vitro and preclinical models, and no human clinical trials have been completed to establish pharmacokinetic, safety, or efficacy parameters for exogenous humanin administration.

NAD+ is a coenzyme central to cellular energy metabolism, serving as an electron carrier in glycolysis, the citric acid cycle, and oxidative phosphorylation. It is also a required substrate for sirtuins (SIRT1–7) and PARP enzymes, which regulate DNA repair, gene expression, and mitochondrial biogenesis. NAD+ levels decline measurably with age; IV or subcutaneous delivery aims to restore intracellular pools more directly than oral precursors such as NMN or NR.

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in every cell, central to energy production, DNA repair, and sirtuin activation. While not a peptide in the traditional sense, it is widely administered by functional medicine and longevity providers via intravenous infusion or subcutaneous injection. Research interest centres on its role in mitochondrial health, cellular resilience, and neurological function as NAD+ levels decline with age. NAD+ IV therapy: intravenous NAD+ infusion is the administration route that has attracted the most clinical interest, particularly in longevity and functional medicine contexts. IV NAD+ therapy delivers the compound directly into the bloodstream, bypassing digestive absorption — a route considered relevant given that oral NAD+ precursors (NMN, NR) have variable bioavailability. NAD+ IV therapy cost typically ranges from $200–$1,000 per session depending on the clinic, infusion volume, and geographic market; treatment frequency in clinical settings commonly ranges from weekly to monthly maintenance infusions following an initial loading protocol. NAD+ IV therapy clinics operate across major US markets including Houston, Los Angeles, New York, and Las Vegas. For those researching where to find NAD+ IV therapy providers, PeptideBase maintains a directory of verified clinics and telehealth platforms offering NAD+ protocols.