Humanin

In cell and animal models, humanin is described as a cytoprotective, anti-apoptotic signaling peptide. The discussed modes of action include inhibition of the pro-apoptotic protein BAX, binding to the insulin-like growth factor binding protein IGFBP-3, and activation of survival signaling pathways (including STAT3, ERK1/2 and AKT signaling). Through these routes, humanin is thought to protect cells from various stress and toxicity stimuli, such as amyloid-beta-induced neuronal cell death. These mechanisms are characterized predominantly in vitro and in animal models; how relevant they are for the intact human organism has not been conclusively clarified.

A large part of the data comes from cell culture and animal models as well as from the potent analogue HNG; statements on pharmacokinetics and dose-response in humans are not established.

Humanin was described in 2001 by the research group of Hashimoto and Nishimoto (Keio University, Japan) during the search for factors that protect nerve cells from Alzheimer's-associated insults — hence the name. A follow-up paper published in 2002 in Neuroscience Letters provided evidence of endogenous production of the peptide and its possible role in Alzheimer's disease (PMID 12009529). In the following years, humanin was classified as the first member of the mitochondria-derived peptides, and the research field expanded to metabolism, the cardiovascular system, eye diseases and aging. Later work linked humanin to lifespan and healthspan in animal models as well as to age-dependent blood levels in humans.

• Neuroprotection and neurodegenerative diseases (including Alzheimer's models, amyloid-beta toxicity)
• Aging, lifespan and healthspan (mitochondria-derived peptides)
• Metabolism and insulin action (metabolic research models)
• Cardiovascular and eye research (protection against cellular stress in models)
• Humanin as a possible age-dependent biomarker in the blood

• Documented in cell and animal models: anti-apoptotic and cytoprotective effects (including BAX inhibition, STAT3 activation).
• Neuroprotective and metabolic effects described in preclinical models (predominantly with the analogue HNG).
• In humans: an observed association of lower blood levels with higher age and with diseases such as Alzheimer's and MELAS — as a correlation, not as a proven effect of administration.