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Review
. 2020 Oct 5:11:554994.
doi: 10.3389/fendo.2020.554994. eCollection 2020.

Caenorhabditis elegans as a Useful Model for Studying Aging Mutations

Siwen Zhang  1 , Fei Li  1 , Tong Zhou  1 , Guixia Wang  1 , Zhuo Li  1
Affiliations
Review

Caenorhabditis elegans as a Useful Model for Studying Aging Mutations

Siwen Zhang et al. Front Endocrinol (Lausanne). .

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.

Keywords: AMPK; IGF-1; dietary restriction; drug screening; mTOR.

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Figures

Figure 1
Figure 1
Major longevity pathways and longevity-associated transcription factors in C. elegans. The IIS pathway is one of the most studied longevity pathways. DAF-2, AGE-1, and DAF-16 are its three key genes. Mutations in DAF-2 and AGE-1 and low IIS activity prolong lifespan via DAF-16 and downstream gene expression. AMPK is another crucial metabolic energy sensor that links nutrient availability to lifespan by binding and phosphorylating a set of transcriptional (co)activators. The mTOR pathway is another critical pathway that links nutrient availability and metabolism to longevity; however, its mechanism remains to be fully elucidated (, –49).
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