IGF‐I regulates the age‐dependent signaling peptide humanin

Aging Cell

Changhan Lee²  Junxiang Wan²  Brian Miyazaki³  Yimin Fang¹  Jaime Guevara-Aguirre⁴  Kelvin Yen²  Valter Longo²  Andrzej Bartke¹ 

[1] Geriatrics Laboratory, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA;Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA;Children's Hospital Los Angeles, Los Angeles, CA, USA;Universidad San Francisco de Quito, Avenida Vía Láctea en Cumbayá, Quito, Ecuador

关键词: aging;    growth hormone;    humanin;    IGF‐I;    longevity;   

DOI  :  10.1111/acel.12243

来源: Wiley

【 摘 要 】

Summary

Aging is influenced by endocrine pathways including the growth hormone/insulin-like growth factor-1 (GH/IGF) axis. Mitochondrial function has also been linked to the aging process, but the relevant mitochondrial signals mediating the effects of mitochondria are poorly understood. Humanin is a novel signaling peptide that acts as a potent regulator of cellular stress responses and protects from a variety of in vitro and in vivo toxic and metabolic insults. The circulating levels of humanin decline with age in mice and humans. Here, we demonstrate a negative correlation between the activity of the GH-IGF axis and the levels of humanin, as well as a positive correlation between humanin and lifespan in mouse models with altered GH/IGF-I axis. Long-lived, GH-deficient Ames mice displayed elevated humanin levels, while short-lived GH-transgenic mice have reduced humanin levels. Furthermore, treatment with GH or IGF-I reduced circulating humanin levels in both mice and human subjects. Our results indicate that GH and IGF are potent regulators of humanin levels and that humanin levels correlate with lifespan in mice. This suggests that humanin represents a circulating mitochondrial signal that participates in modulating the aging process, adding a coordinated mitochondrial element to the endocrine regulation of aging.

【 授权许可】

CC BY   
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.