Humanin

✓Key benefits

📈What to expect

Based on community reports and published research. Individual results vary significantly.

💊Dosing protocols

Dosing information is sourced from published research and community protocols. This is not a recommendation. Consult a healthcare professional.

Overview

Humanin was discovered in 2001 by Nishimoto and colleagues while screening for genes that could rescue neurons from amyloid-beta toxicity in Alzheimer's disease. It is encoded within the 16S ribosomal RNA gene of mitochondrial DNA, making it one of the first 'mitochondrial-derived peptides' (MDPs) identified. Circulating humanin levels decline with age and are inversely correlated with age-related diseases. Centenarian studies have found higher humanin levels in exceptionally long-lived individuals and their offspring. It has since been implicated in insulin sensitivity, cardiovascular protection, and stress resistance across multiple organ systems.

⚙️How it works

Humanin signals through multiple receptors, including the FPRL-1 receptor (a formyl peptide receptor) and a trimeric receptor complex consisting of CNTFR, WSX-1, and gp130. Through these receptors, it activates STAT3 signalling and inhibits apoptotic pathways (specifically Bax-mediated mitochondrial apoptosis). It also improves insulin sensitivity by activating AMPK and reducing hepatic glucose output. At the mitochondrial level, humanin enhances oxidative phosphorylation efficiency and reduces reactive oxygen species (ROS) production, acting as a retrograde signal from stressed mitochondria to the rest of the cell.

⚡Side effects

📅Research history

Mitochondrial-derived peptides: a new class

Humanin was the founding member of mitochondrial-derived peptides (MDPs) - small bioactive peptides encoded within mitochondrial DNA. Since its discovery, other MDPs have been identified including MOTS-c (also in this database) and SHLPs (Small Humanin-Like Peptides 1-6). These peptides represent a form of retrograde signalling: when mitochondria are stressed, they produce signalling molecules that communicate with the nucleus and other cells. This discovery has reframed mitochondria from simple energy producers to active signalling organelles with direct roles in aging and disease.

Humanin and centenarian studies

Research from the Albert Einstein College of Medicine found that circulating humanin levels are significantly higher in centenarians and their offspring compared to age-matched controls. Humanin levels decline naturally with age, and this decline correlates with increased susceptibility to Alzheimer's disease, type 2 diabetes, and cardiovascular disease. These observational findings have driven interest in humanin as both a biomarker of biological age and a potential therapeutic target. However, it remains unclear whether high humanin levels cause longevity or are simply a marker of healthy mitochondrial function.

References

1. [1]Hashimoto Y, et al. 'A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta.' Proceedings of the National Academy of Sciences, 2001.
2. [2]Muzumdar RH, et al. 'Humanin: a novel central regulator of peripheral insulin action.' PLoS ONE, 2009.

Frequently asked questions

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