The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans

Louis R. Lapierre, C. Daniel De Magalhaes Filho, Philip R. McQuary, Chu-Chiao Chu, Orane Visvikis, Jessica T. Chang, Sara Gelino, Binnan Ong, Andrew E. Davis, Javier E. Irazoqui, Andrew Dillin and Malene Hansen ()
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Louis R. Lapierre: Program of Development and Aging, Del E Webb Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute
C. Daniel De Magalhaes Filho: The Howard Hughes Medical Institute, The Glenn Center for Aging Research, The Salk Institute for Biological Studies
Philip R. McQuary: Program of Development and Aging, Del E Webb Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute
Chu-Chiao Chu: Program of Development and Aging, Del E Webb Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute
Orane Visvikis: Massachusetts General Hospital, Harvard Medical School
Jessica T. Chang: Program of Development and Aging, Del E Webb Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute
Sara Gelino: Program of Development and Aging, Del E Webb Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute
Binnan Ong: Program of Development and Aging, Del E Webb Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute
Andrew E. Davis: Program of Development and Aging, Del E Webb Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute
Javier E. Irazoqui: Massachusetts General Hospital, Harvard Medical School
Andrew Dillin: The Howard Hughes Medical Institute, The Glenn Center for Aging Research, The Salk Institute for Biological Studies
Malene Hansen: Program of Development and Aging, Del E Webb Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute

Nature Communications, 2013, vol. 4, issue 1, 1-8

Abstract: Abstract Autophagy is a cellular recycling process that has an important anti-aging role, but the underlying molecular mechanism is not well understood. The mammalian transcription factor EB (TFEB) was recently shown to regulate multiple genes in the autophagy process. Here we show that the predicted TFEB orthologue HLH-30 regulates autophagy in Caenorhabditis elegans and, in addition, has a key role in lifespan determination. We demonstrate that hlh-30 is essential for the extended lifespan of Caenorhabditis elegans in six mechanistically distinct longevity models, and overexpression of HLH-30 extends lifespan. Nuclear localization of HLH-30 is increased in all six Caenorhabditis elegans models and, notably, nuclear TFEB levels are augmented in the livers of mice subjected to dietary restriction, a known longevity-extending regimen. Collectively, our results demonstrate a conserved role for HLH-30 and TFEB in autophagy, and possibly longevity, and identify HLH-30 as a uniquely important transcription factor for lifespan modulation in Caenorhabditis elegans.

Date: 2013
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DOI: 10.1038/ncomms3267

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