Role of the GH/IGF-1 axis in lifespan and healthspan: Lessons from animal models

被引:209
作者
Berryman, Darlene E. [1 ]
Christiansen, Jens Sandahl [2 ]
Johannsson, Gudmundur [3 ]
Thorner, Michael O. [4 ]
Kopchick, John J. [5 ,6 ]
机构
[1] Ohio Univ, Coll Hlth & Human Serv, Sch Human & Consumer Sci, Athens, OH 45701 USA
[2] Aarhus Univ Hosp, Kommunehosp, Dept Endocrinol, DK-8000 Aarhus, Denmark
[3] Sahlgrens Univ Hosp, Res Ctr Endocrinol & Metab, S-41345 Gothenburg, Sweden
[4] Univ Virginia Hlth Syst, Charlottesville, VA 22908 USA
[5] Ohio Univ, Dept Biomed Sci, Konneker Res Labs, Coll Osteopath Med, Athens, OH 45701 USA
[6] Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA
关键词
Growth hormone; Insulin like growth factor 1; Aging; Mouse models; Lifespan; Longevity genes; Intracellular signaling pathways; Healthspan;
D O I
10.1016/j.ghir.2008.05.005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Animal models are fundamentally important in our quest to understand the genetic, epigenetic, and environmental factors that Contribute to human aging. In comparison to humans, relatively short-lived mammals are useful models as they allow for rapid assessment of both genetic manipulation and environmental intervention as related to longevity. These models also allow for the Study of clinically relevant pathologies as a function of aging. Data associated with more distant species offers additional insight and critical consideration of the basic physiological processes and molecular mechanisms that influence lifespan. Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor-1 (IGI-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations call keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages. In this review, we will provide all overview of how the manipulation of the GH/IGF axis influences lifespan, highlight the invertebrate and vertebrate animal models with altered lifespan due to modifications to the GH/IGF-1 signaling cascade or homologous pathways, and discuss the basic phenotypic characteristics and healthspan of these models. Published by Elsevier Ltd.
引用
收藏
页码:455 / 471
页数:17
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