AMP-activated protein kinase and FoxO transcription factors in dietary restriction-induced longevity

Eric L. Greer, Max R. Banko, Anne Brunet

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

104 Scopus citations

Abstract

Aging is regulated by modiications in single genes and by simple changes in the environment. The signaling pathway connecting insulin to FoxO transcription factors integrates environmental stimuli to regulate lifespan. FoxO transcription factors are directly phosphorylated in response to insulingrowth factor signaling by the protein kinase Akt, thereby causing their sequestration in the cytoplasm. In the absence of insulingrowth factors, FoxO factors translocate to the nucleus where they trigger a range of cellular responses, including resistance to oxidative stress - a phenotype highly coupled with lifespan extension. Our recent results indicate that FoxO transcription factors are also regulated in response to nutrient deprivation by the AMP-activated protein kinase (AMPK) pathway. The energy-sensing AMPK directly phosphorylates FoxO transcription factors at six regulatory sites. AMPK phosphorylation enhances FoxO transcriptional activity, leading to the expression of specific target genes involved in stress resistance and changes in energy metabolism. The AMPK-FoxO pathway plays a crucial role in the ability of a dietary restriction regimen to extend lifespan in Caenorhabditis elegans. Understanding the intricate signaling networks that translate environmental conditions like dietary restriction into changes in gene expression that extend lifespan will be of critical importance to identify ways to delay the onset of aging and age-dependent diseases.

Original languageEnglish
Title of host publicationInternational Symposium on Olfaction and Taste
PublisherBlackwell Publishing Inc.
Pages688-692
Number of pages5
ISBN (Print)9781573317382
DOIs
StatePublished - Jul 2009

Publication series

NameAnnals of the New York Academy of Sciences
Volume1170
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • AMPK
  • Aging
  • Caloric restriction
  • Dietary restriction
  • FoxO
  • Longevity

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