A PTEN variant uncouples longevity from impaired development in insulin/IGF-1 receptor mutant C. elegans

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Activation of FOXO and HSF-1 promotes immunocompetence in old C. elegans via overriding p38 MAPK-dependent immunosenescence

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A point mutation in daf-18/PTEN uncouples longevity and developmental defects in da-2/insulin/IGF-1 receptor mutant

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A point mutation in PTEN uncouples longevity and defects in insulin/IGF-1 receptor mutants

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Inhibition of elongin C promotes longevity and protein homeostasis via HIF

The transcription factor hypoxia‐inducible factor 1 (HIF‐1) is crucial for responses to low oxygen and promotes longevity in Caenorhabditis elegans. We previously performed a genomewide RNA interference screen and identified many genes that act as potential negative regulators of HIF‐1. Here, we functionally characterized these genes and found several novel genes that affected lifespan. The worm ortholog of elongin C, elc‐1, encodes a subunit of E3 ligase and transcription elongation factor. We found that knockdown of elc‐1 prolonged lifespan and delayed paralysis caused by impaired protein homeostasis. We further showed that elc‐1 RNA interference increased lifespan and protein homeostasis by upregulating HIF‐1. The roles of elongin C and HIF‐1 are well conserved in eukaryotes. Thus, our study may provide insights into the aging regulatory pathway consisting of elongin C and HIF‐1 in complex metazoans

Glutamine tRNA-derived fragments increase lifespan by enhencing mitochondrial function in Caenorhabditis elegans

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Slow growth positively correlates with long adult lifespan among wild C. elegans strains

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KIN-4/protein kinase influences insulin/IGF-1 signaling-mediated longevity via interacting with DAF-18/PTEN in C. elegans

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Genes and pathways that influence longevity in Caenorhabditis elegans

The roundworm Caenorhabditis elegans is one of the most popular model organisms for research on aging because of its short lifespan and genetic tractability. Studies using C. elegans have identified many genes and pathways that regulate aging, several of which are conserved in other species, including mammals. In this chapter, we describe longevity-regulatory pathways including insulin/IGF-1 (insulin-like growth factor 1) signaling, TOR (target of rapamycin) signaling, autophagy, mitochondrial respiration, and HIF-1 (hypoxia-inducible factor 1) pathways. We also review the effects of dietary restriction, a key environmental factor that influences aging, on longevity-regulatory genetic factors. In addition, we illustrate the roles of two important C. elegans tissues, those of the sensory neural and reproductive systems, in regulating longevity at the molecular level. For each of the subtopics, we explain how changes in the expression of genes involved in each pathway and system alter longevity.We also speculate on the evolutionary significance of the genes and pathways that affect longevity. Given the conserved nature of longevity regulation, the dissection of the roles of these genetic factors in determining the C. elegans lifespan will provide important clues for understanding the secrets of human aging. © Springer Japan 2015.1

Glutamine 5’-tRNA-drived small RNAs promote longevity via increasing mitochondrial activity through AMPK

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