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Dev Cell,
2004]
Genetic experiments in C. elegans suggested that SIR2, an NAD-dependent protein deacetylase, acts through FOXO/DAF-16 transcription factor to prolong life. Recent studies show that mammalian SIR2 deacetylates FOXO, and may maximize survival by tempering cell death and increasing stress resistance.
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WormBook,
2015]
Nuclear receptors are transcription factors that often respond to small molecule metabolites and fat-soluble compounds to regulate gene expression. They broadly govern development, reproduction, metabolism, and homeostasis in diverse metazoan species and their dysregulation is associated with numerous diseases. Work in C. elegans has shed light on the seminal role of nuclear receptors in life history regulation, stem cell progression, developmental timing, cell fate specification, nutrient sensing, metabolism, and longevity. Here we highlight recent advances on the best-studied nuclear receptors in the worm, and how they illuminate metazoan biology.
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PLoS Genet,
2007]
A dissection of longevity in Caenorhabditis elegans reveals that animal life span is influenced by genes, environment, and stochastic factors. From molecules to physiology, a remarkable degree of evolutionary conservation is seen.
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Exp Gerontol,
2013]
Pioneering work in model organisms reveals that the reproductive system is involved not only in propagation of the species but also regulates organismal metabolism and longevity. In C. elegans, prevention of germline stem cell proliferation results in a 60% extension of lifespan, termed gonadal longevity. Gonadal longevity relies on the transcriptional activities of steroid nuclear receptor DAF-12, the FOXO transcription factor homolog DAF-16, the FOXA transcription factor homolog PHA-4, and the HNF-4-like nuclear receptor NHR-80. These transcription factors work in an integrated transcriptional network to regulate fatty acid lipolysis, autophagy, stress resistance and other processes, which altogether enhance homeostasis and extend life. Because the reproductive system also regulates longevity in other species, studies in C. elegans may shed light on ancient mechanisms governing reproduction and survival.
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Cell Metab,
2005]
In C. elegans, dauer pheromone is an indicator of population density and influences pathways that regulate metabolism, development, and aging. In a recent publication in Nature, Paik and coworkers (Jeong et al., 2005) show the purified substance to be a pyran ring conjugated to heptanoic acid, setting the stage for dissecting downstream signaling pathways.
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Curr Biol,
2019]
A new study finds that signaling pathways promoting developmental quiescence can reprogram developmental time.
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[
Neuron,
2004]
Insulin/IGF signaling has emerged as a central regulator of metazoan aging. In C. elegans, insulin-like peptides are expressed predominately in neurons. Alcedo and Kenyon demonstrate that removal of specific gustatory and olfactory neurons result in longer life, suggesting that metazoan longevity is influenced by sensory perception.