Humanin is a tiny protein made by mitochondria that can protect brain cells and may help with many diseases. It interacts with the IGF‑I system – it can bind a binding protein (IGFBP‑3) and lower blood IGF‑I levels, while IGF‑I itself seems to control how much humanin is made. The exact back‑and‑forth mechanism isn’t fully worked out yet, but humanin is now seen as a new player in IGF‑I signaling.

Humanin is the first newly discovered peptide encoded in the mitochondrial genome in over three decades. It is the first member of a novel class of mitochondrial derived peptides. This small, 24 amino acid peptide was initially discovered to have neuroprotective effects and subsequent experiments have shown that it is beneficial in a diverse number of disease models including stroke, cardiovascular disease, and cancer. Over a decade ago, our lab found that humanin bound IGFBP-3 and more recent studies have found it to decrease circulating IGF-I levels. In turn, IGF-I also seems to regulate humanin levels and in this review, we cover the known interaction between humanin and IGF-I. Although the exact mechanism for how humanin and IGF-I regulate each other still needs to be elucidated, it is clear that humanin is a new player in IGF-I signaling.