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Studying FOXO, a family of transcription factors that inhibits aging Center for Plant Aging Research

A majority of previous studies on aging and longevity have focused on DNA and proteins. However, little has been done to explore the role of RNA – a polymeric molecule that conveys genetic code-in the aging process. In addition, the functional significance of RNA helicases, a large family of enzymes essential for regulating the biogenesis and homeostasis of RNA, remains unknown in terms of aging and lifespan regulation. The Center for Plant Aging Research within IBS (Director Hong Gil Nam) separated 78 RNA helicases Caenorhabditis elegans, an animal aging model species by performing a large-scale RNAi screening and investigated their role in aging and lifespan regulation. The result showed that approximately 40% of the helicases were involved in aging and lifespan regulation. In particular, the research team unveiled for the first time that RNA helicase 1 (HEL-1) plays a pivotal role in longevity and lifespan regulation. Further, profound research of HEL-1 functions confirmed that when using RNAi to suppress HEL-1 functions of the Caenorhabditis elegans daf-2 mutant whose lifespan doubles the wild C. elegans, its lifespan decreased by nearly 39%, while over-expressing HEL-1 in C.elegans resulted in an increase in its lifespan by up to 18%.

Anti-aging mechanism of various animals

Anti-aging mechanism of various animals Yeast, nematodes, and drosophilae are widely used for research on aging because the aging delay factors observed in those organisms are also found in mammals. It has been discovered so far that a certain signaling transduction system is repressed by amounts of extracellular nutrients, activating aging delay factors. FOXO primarily works in the aging of drosophilae and mammals, and also plays an influential role in the aging of nematodes.

In the case of C. elegans, its insulin receptor activated by insulin disables the function of FOXO transcription factor so that genes essential for longevity cannot be transcribed to RNA. On the other hand, mutants with the degraded functions of an insulin receptor see their lifespan increase by at least two times that of wild C. elegans. It is because the inhibitors of the function of FOXO transcription factor are weakened. In nematodes, FOXO is highly associated with lipoclasis and autophagy. The left illustration shows the difference of aging delay mechanism between daf-2 and TOR mutants.
This research confirms that FOXO transcription factors interact with HEL-1 (RNA helicase) for their activation and function performance, and the interactions play a significant role in expression of genes necessary for longevity.

An overview of the experiment

Published paper

Mihwa Seo et al., “RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans ”, Proceedings of the National Academy of Sciences , E4246-E4255, 2015
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Last Update 2023-11-28 14:20