The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan
Kelvin Yen, Hemal H. Mehta, Su‐Jeong Kim, Yanhe Lue, James Hoang, Noel Guerrero, Jenna Port, Qiuli Bi, Gerardo Navarrete, Sebastian Brandhorst, Kaitlyn N. Lewis, Junxiang Wan, Ronald S. Swerdloff, Julie A. Mattison, Rochelle Buffenstein, Carrie V. Breton, Christina Wang, Valter D. Longo, Gil Atzmon, Douglas C. Wallace, Nir Barzilai, Pinchas Cohen
Abstract
. Humanin transgenic mice have many phenotypes that overlap with the worm phenotypes and, similar to exogenous humanin treatment, have increased protection against toxic insults. Treating middle-aged mice twice weekly with the potent humanin analogue HNG, humanin improves metabolic healthspan parameters and reduces inflammatory markers. In multiple species, humanin levels generally decline with age, but here we show that levels are surprisingly stable in the naked mole-rat, a model of negligible senescence. Furthermore, in children of centenarians, who are more likely to become centenarians themselves, circulating humanin levels are much greater than age-matched control subjects. Further linking humanin to healthspan, we observe that humanin levels are decreased in human diseases such as Alzheimer's disease and MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes). Together, these studies are the first to demonstrate that humanin is linked to improved healthspan and increased lifespan.