期刊
CELL CYCLE
卷 7, 期 21, 页码 3338-3343出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.7.21.7012
关键词
longevity; insulin; signaling; FIRKO mouse; IGF-1; aging
类别
资金
- NIA [AG 19899, U19 AG023122]
- Ellison Medical Foundation
- Glenn Foundation for Medical Research
- SIU Geriatrics Initiative
In invertebrates, signaling pathways homologous to mammalian insulin and insulin-like growth factor (IGF-1) signal transduction have a major role in the control of longevity. There are numerous indications that these pathways also influence aging in mammals, but separating the role of insulin from the effects of IGF-1 and growth hormone (GH) is difficult. In mice, selective disruption of the insulin receptor in the adipose tissue extends longevity. Increases in lifespan were also reported in mice with deletion of insulin receptor substrate 1 (IRS1) in whole body or IRS2 only in the brain. GH deficiency or resistance in mutant mice leads to hypoinsulinemia and enhanced insulin sensitivity along with remarkably extended longevity. These characteristics resemble animals subjected to calorie restriction. Studies of physiological characteristics and polymorphisms of insulin-related genes in exceptionally long-lived people suggest a role of insulin signaling in the control of human aging.
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