Humanin

Humanin is an exception among peptides: its blueprint does not sit in the cell nucleus but in mitochondrial DNA, more precisely in the gene for the 16S rRNA. The 24-amino-acid molecule caught the attention of groups around Yuichi Hashimoto in 2001 while they were searching for factors that keep nerve cells safe from Alzheimer-type toxicity: Humanin abolished the cell death triggered by familial Alzheimer's disease genes and amyloid-beta.

How it acts, in brief:

• Binding to several receptors, among them formyl peptide receptor 2, and to the binding protein IGFBP-3; the interaction with IGFBP-3 regulates cell survival and apoptosis.
• Inhibition of apoptosis, protection against oxidative stress and neuroprotective effects, best documented in Alzheimer models.
• Better insulin sensitivity in animal models; together with MOTS-c, Humanin counts as an age-dependent regulator of apoptosis, insulin sensitivity and inflammatory markers.

Humanin levels fall with age. From that observation a line of research has grown that tests whether supplementing it slows ageing processes: in mouse studies, sustained dosing extended median lifespan, and a 2018 paper tied Humanin to less cognitive decline with age in mice and to a better cognitive age in humans.

Pharmacokinetically the native peptide is impractical because it is broken down very quickly. Analogs such as HNG (Humanin with a glycine at position 14) were developed to stay in the body for longer.

Humanin is described as well tolerated in studies; as a peptide of the body's own making, it stands in the preclinical literature mostly for cell-protective effects. What you should keep in mind:

• Injection site: mild redness or a feeling of pressure is the most common observation with peptides given under the skin.
• Short half-life: the native form acts only very briefly, which makes steering the effect harder; that is what the synthetic analogs were developed for.
• Metabolism: the effects on insulin sensitivity are systemic and go beyond pure neuroprotection.
• Data situation: the evidence comes mostly from animal models, and there are no long-term human studies.

This summary is no substitute for medical advice.

• A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta - the discovery paper: Humanin as a rescue factor against nerve cell death caused by familial Alzheimer genes and amyloid-beta.
• Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers - Humanin and MOTS-c as age-dependent regulators of apoptosis, insulin sensitivity and inflammatory markers.
• Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans - less cognitive decline with age in mice, and in humans a link to cognitive age.