title: IGF-I regulates the age-dependent signaling peptide humanin.
abstract: 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.
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90089, USA.
authors.forename: Changhan
authors.initials: C
authors.lastname: Lee
authors.forename: Junxiang
authors.initials: J
authors.lastname: Wan
authors.forename: Brian
authors.initials: B
authors.lastname: Miyazaki
authors.forename: Yimin
authors.initials: Y
authors.lastname: Fang
authors.forename: Jaime
authors.initials: J
authors.lastname: Guevara-Aguirre
authors.forename: Kelvin
authors.initials: K
authors.lastname: Yen
authors.forename: Valter
authors.initials: V
authors.lastname: Longo
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
mesh_terms: D000367:Age Factors; D000818:Animals; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C427211:humanin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
keywords: IGF-I; aging; growth hormone; humanin; longevity