Converging Pathways in Lifespan Regulation

被引:126
作者
Narasimhan, Sri Devi [1 ]
Yen, Kelvin [1 ]
Tissenbaum, Heidi A. [1 ,2 ]
机构
[1] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA
[2] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA
关键词
RESTRICTION-INDUCED LONGEVITY; FOXO TRANSCRIPTION FACTORS; CAENORHABDITIS-ELEGANS; DIETARY RESTRICTION; CALORIC RESTRICTION; ENDOCRINE REGULATION; SIGNALING PATHWAY; MAMMALIAN TARGET; STRESS-RESPONSE; HUMAN INSULIN;
D O I
10.1016/j.cub.2009.06.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The processes that determine an organism's lifespan are complex and poorly understood. Yet single gene manipulations and environmental interventions can substantially delay age-related morbidity. In this review, we focus on the two most potent modulators of longevity: insulin/insulin-like growth factor 1 (IGF-1) signaling and dietary restriction. The remarkable molecular conservation of the components associated with insulin/IGF-1 signaling and dietary restriction allow us to understand longevity from a multi-species perspective. We summarize the most recent findings on insulin/IGF-1 signaling and examine the proteins and pathways that reveal a more genetic basis for dietary restriction. Although insulin/IGF-1 signaling and dietary restriction pathways are currently viewed as being independent, we suggest that these two pathways are more intricately connected than previously appreciated. We highlight that numerous interactions between these two pathways can occur at multiple levels. Ultimately, both the insulin/IGF-1 pathway and the pathway that mediates the effects of dietary restriction have evolved to respond to the nutritional status of an organism, which in turn affects its lifespan.
引用
收藏
页码:R657 / R666
页数:10
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