Inhibition of histone acetyltransferase GCN5 extends lifespan in both yeast and human cell lines.

Aging Cell
Boyue HuangZhengwei Xie

Abstract

Histone acetyltransferases (HATs) are important enzymes that transfer acetyl groups onto histones and thereby regulate both gene expression and chromosomal structures. Previous work has shown that the activation of sirtuins, which are histone deacetylases, can extend lifespan. This suggests that inhibiting HATs may have a similar beneficial effect. In the present study, we utilized a range of HAT inhibitors or heterozygous Gcn5 and Ngg1 mutants to demonstrate marked yeast life extension. In human cell lines, HAT inhibitors and selective RNAi-mediated Gcn5 or Ngg1 knockdown reduced the levels of aging markers and promoted proliferation in senescent cells. Furthermore, this observed lifespan extension was associated with the acetylation of histone H3 rather than that of H4. Specifically, it was dependent upon H3K9Ac and H3K18Ac modifications. We also found that the ability of caloric restriction to prolong lifespan is Gcn5-, Ngg1-, H3K9-, and H3K18-dependent. Transcriptome analysis revealed that these changes were similar to those associated with heat shock and were inversely correlated with the gene expression profiles of aged yeast and aged worms. Through a bioinformatic analysis, we also found that HAT inhibition activated sub...Continue Reading

References

Jan 19, 2000·Trends in Biochemical Sciences·C E BrownJ L Workman
Mar 5, 2003·Cellular and Molecular Life Sciences : CMLS·M ZafarullahM Ahmad
Apr 3, 2003·Nature Reviews. Molecular Cell Biology·Siavash K Kurdistani, Michael Grunstein
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Nov 1, 2005·Developmental Cell·Mohan ViswanathanLeonard Guarente
Mar 8, 2007·JAMA : the Journal of the American Medical Association·Luigi Fontana, Samuel Klein
Mar 17, 2007·Nature Reviews. Genetics·María A Blasco
Mar 24, 2007·Nature Reviews. Molecular Cell Biology·Kenneth K Lee, Jerry L Workman
Mar 12, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Wenchu LinSharon Y R Dent
Jun 12, 2009·Nature·Weiwei DangShelley L Berger
Jul 18, 2009·Genes & Development·Alejandro Vaquero, Danny Reinberg
Jul 18, 2009·EMBO Reports·Susana Rodríguez-Navarro
Mar 8, 2012·Nature Reviews. Molecular Cell Biology·Riekelt H HoutkooperJohan Auwerx
Jun 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Benjamin P CasavantDavid J Beebe
Jun 12, 2013·Cell·Carlos López-OtínGuido Kroemer
Aug 12, 2014·Molecular & Cellular Proteomics : MCP·Anne M CieniewiczSean D Taverna
Nov 18, 2014·ELife·Annina Denoth-LippunerYves Barral
Jul 15, 2015·Proceedings of the National Academy of Sciences of the United States of America·Myeong Chan JoLidong Qin
Sep 17, 2015·Nature Reviews. Molecular Cell Biology·Bérénice A BenayounAnne Brunet

❮ Previous
Next ❯

Citations

Mar 4, 2021·Ageing Research Reviews·Elena G PasyukovaAlexander M Vaiserman

❮ Previous
Next ❯

Methods Mentioned

BETA
acetylation
histone acetylation
chips
chip
deubiquitination
PCR
Transfection
gel filtration
electrophoresis

Software Mentioned

GraphPad Prism

Related Concepts

Related Feeds

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.