Forward and reverse genetics approaches to uncover metabolic aging pathways in Caenorhabditis elegans

Biochim Biophys Acta Mol Basis Dis. 2018 Sep;1864(9 Pt A):2697-2706. doi: 10.1016/j.bbadis.2017.09.006. Epub 2017 Sep 15.

Abstract

The biological mechanisms of aging have been studied in depth and prominent findings in this field promote the development of new therapies for age-associated disorders. Various model organisms are used for research on aging; among these, the nematode Caenorhabditis elegans has been widely used and has provided valuable knowledge in determining the regulatory mechanisms driving the aging process. Many genes involved in lifespan regulation are associated with metabolic pathways and are influenced by genetic and environmental factors. In line with this, C. elegans provides a promising platform to study such gene by environment interactions, in either a reverse or forward genetics approach. In this review, we discuss longevity mechanisms related to metabolic networks that have been discovered in C. elegans. We also highlight the use of wild populations to study the complex genetic basis of natural variation for quantitative traits that mediate longevity.

Keywords: Aging; C. elegans; Forward genetics; Gene×environment interaction; Metabolism; QTL mapping.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Aging / genetics*
  • Aging / physiology*
  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / physiology*
  • Gene-Environment Interaction
  • Insulin
  • Insulin-Like Growth Factor I
  • Longevity / genetics
  • Longevity / physiology
  • Metabolic Networks and Pathways*
  • Mitochondria / physiology
  • Models, Animal
  • Phenotype
  • Research
  • Reverse Genetics / methods*
  • Signal Transduction
  • Sirtuins / classification
  • Sirtuins / genetics
  • Sirtuins / metabolism
  • Stress, Physiological
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Insulin
  • Insulin-Like Growth Factor I
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Sirtuins