Humanin

Humanin is a 21-amino-acid peptide encoded within mitochondrial DNA, discovered in 2001 as a survival factor that protects neurons from Alzheimer's-associated cell death. It is part of the same family as MOTS-c — mitochondria-derived peptides (MDPs) that act as endocrine signals coordinating metabolic stress responses. Blood levels decline with age and are reduced in cancer patients.

Properties

Amino Acid Sequence

MAPRGFSCLLLLTSEIDLPVKRRA

Origin: Encoded within the mitochondrial 16S ribosomal RNA gene; naturally occurring mitokine

Binds to and activates the gp130 receptor family (IL-6 receptor), triggering STAT3 and MAPK protective cascades. Inhibits BAX (a pro-apoptotic protein) from entering mitochondria, protecting normal cells. Also activates AMPK and suppresses IGF-1 signalling. Reduces oxidative stress via NF-κB inhibition. In cancer cells (unlike normal cells) it may paradoxically promote apoptosis by a different mechanism involving gp130 tumour suppressor signalling.

Emerging evidence suggests Humanin has a protective role against treatment toxicity: reduces cisplatin-induced kidney toxicity in animal models, protects cardiac cells from doxorubicin damage, and reduces oxaliplatin-associated neuropathy. Also shows direct anti-proliferative effects in prostate cancer and breast cancer cell lines. Serum Humanin levels have been proposed as a cancer prognosis biomarker.

Links open on PubMed (National Library of Medicine). Research is ongoing — results may not reflect clinical use.

• Entirely pre-clinical / early research — no human trials completed
• Dual pro-survival effect: protects normal cells but mechanism in cancer cells is context-dependent
• Research compound only; no regulatory approval
• Very short half-life limits practical utility without delivery system improvements