Abstract
The Caenorhabditis elegans genome possesses homologs of about two-thirds of all human disease genes. Based on its physiological aging characteristics and superiority, the use of C. elegans as a model system for studies on aging, age-related diseases, mechanisms of longevity, and drug screening has been widely acknowledged in recent decades. Lifespan increasing mutations in C. elegans were found to delay aging by impinging several signaling pathways and related epigenetic modifications, including the insulin/IGF-1 signaling (IIS), AMP-activated protein kinase (AMPK), and mechanistic target of rapamycin (mTOR) pathways. Interestingly, dietary restriction (DR) has been shown to increase the lifespan of numerous metazoans and protect them from multiple age-related pathologies. However, the underlying molecular mechanisms are unclear. In recent decades, C. elegans has been used as a unique model system for high-throughput drug screening. Here, we review C. elegans mutants exhibiting increased in lifespan and age-dependent changes under DR, as well as the utility of C. elegans for drug screening. Thus, we provide evidence for the use of this model organism in research on the prevention of aging.
Highlights
The eukaryotic multicellular organism Caenorhabditis elegans which has completely sequenced genetic profile, is an established genetic model organism [1], that can be used to study aging
In worms with the daf-2 mutation, the activity of the insulin/IGF-1 signaling (IIS) pathway decrease leading to the phosphorylation of DAF-16 by AKT-1/2 and the translocation of DAF-16 into the nucleus to bind and initiate expression of target genes, the lifespan of the worm is prolonged and stress-protective mechanisms, including the unfolded protein response and oxidative stress responses, are initiated [29]
Mechanistic Target of Rapamycin Signaling. Another critical pathway linking nutrient availability and metabolism to longevity is the mechanistic target of rapamycin pathway
Summary
Department of Endocrinology and Metabolism, First Affiliated Hospital of Jilin University, Changchun, China Reviewed by: Collin Ewald, ETH Zürich, Switzerland Patrizia D’Aquila, University of Calabria, Italy Specialty section: This article was submitted to Endocrinology of Aging, a section of the journal
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