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Dietary restriction induced longevity is mediated by nuclear receptor NHR-62 in Caenorhabditis elegans.

Bree N Heestand | Yidong Shen | Wei Liu | Daniel B Magner | Nadia Storm | Caroline Meharg | Bianca Habermann | Adam Antebi
PLoS genetics | 2013

Dietary restriction (DR) extends lifespan in a wide variety of species, yet the underlying mechanisms are not well understood. Here we show that the Caenorhabditis elegans HNF4α-related nuclear hormone receptor NHR-62 is required for metabolic and physiologic responses associated with DR-induced longevity. nhr-62 mediates the longevity of eat-2 mutants, a genetic mimetic of dietary restriction, and blunts the longevity response of DR induced by bacterial food dilution at low nutrient levels. Metabolic changes associated with DR, including decreased Oil Red O staining, decreased triglyceride levels, and increased autophagy are partly reversed by mutation of nhr-62. Additionally, the DR fatty acid profile is altered in nhr-62 mutants. Expression profiles reveal that several hundred genes induced by DR depend on the activity of NHR-62, including a putative lipase required for the DR response. This study provides critical evidence of nuclear hormone receptor regulation of the DR longevity response, suggesting hormonal and metabolic control of life span.

Pubmed ID: 23935515

Research resources used in this publication

None found

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Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NIA NIH HHS, United States
    Id: R01 AG027498
  • Agency: NIA NIH HHS, United States
    Id: R01AG027498

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R Project for Statistical Computing (tool)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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ExPANdS (tool)

RRID:SCR_005199

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FASTX-Toolkit (tool)

RRID:SCR_005534

Software tool as collection of command line tools for Short-Reads FASTA/FASTQ files preprocessing.

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Bioinformatic Harvester IV (beta) at Karlsruhe Institute of Technology (tool)

RRID:SCR_008017

Harvester is a Web-based tool that bulk-collects bioinformatic data on human proteins from various databases and prediction servers. It is a meta search engine for gene and protein information. It searches 16 major databases and prediction servers and combines the results on pregenerated HTML pages. In this way Harvester can provide comprehensive gene-protein information from different servers in a convenient and fast manner. As full text meta search engine, similar to Google trade mark, Harvester allows screening of the whole genome proteome for current protein functions and predictions in a few seconds. With Harvester it is now possible to compare and check the quality of different database entries and prediction algorithms on a single page. Sponsors: This work has been supported by the BMBF with grants 01GR0101 and 01KW0013.

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National Institute on Aging (tool)

RRID:SCR_011438

National institute that leads the federal government in conducting and supporting research on aging and the health and well-being of older people. The Institute seeks to understand the nature of aging and the aging process, and diseases and conditions associated with growing older, in order to extend the healthy, active years of life. In 1974, Congress granted authority to form NIA to provide leadership in aging research, training, health information dissemination, and other programs relevant to aging and older people. Subsequent amendments to this legislation designated NIA as the primary Federal agency on Alzheimer's disease research. Mission The Institute's mission is to: * Support and conduct genetic, biological, clinical, behavioral, social, and economic research on aging. * Foster the development of research and clinician scientists in aging. * Provide research resources. * Disseminate information about aging and advances in research to the public, health care professionals, and the scientific community,among a variety of audiences. Programs NIA sponsors research on aging through extramural and intramural programs. The extramural program funds research and training at universities, hospitals, medical centers, and other public and private organizations nationwide. The intramural program conducts basic and clinical research in Baltimore, MD, and on the NIH campus in Bethesda, MD.

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