Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis

PLoS Genet. 2012 Jan;8(1):e1002473. doi: 10.1371/journal.pgen.1002473. Epub 2012 Jan 26.

Abstract

Organismal aging is influenced by a multitude of intrinsic and extrinsic factors, and heterochromatin loss has been proposed to be one of the causes of aging. However, the role of heterochromatin in animal aging has been controversial. Here we show that heterochromatin formation prolongs lifespan and controls ribosomal RNA synthesis in Drosophila. Animals with decreased heterochromatin levels exhibit a dramatic shortening of lifespan, whereas increasing heterochromatin prolongs lifespan. The changes in lifespan are associated with changes in muscle integrity. Furthermore, we show that heterochromatin levels decrease with normal aging and that heterochromatin formation is essential for silencing rRNA transcription. Loss of epigenetic silencing and loss of stability of the rDNA locus have previously been implicated in aging of yeast. Taken together, these results suggest that epigenetic preservation of genome stability, especially at the rDNA locus, and repression of unnecessary rRNA synthesis, might be an evolutionarily conserved mechanism for prolonging lifespan.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Animals
  • Cell Nucleolus / genetics
  • Chromosomal Proteins, Non-Histone / genetics*
  • DNA, Circular / genetics
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / physiology*
  • Epigenesis, Genetic / genetics
  • Genomic Instability
  • Heterochromatin / genetics*
  • Janus Kinases / genetics
  • Janus Kinases / metabolism
  • Longevity / genetics*
  • Muscles / physiology
  • RNA, Ribosomal / biosynthesis*
  • RNA, Ribosomal / genetics
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic / genetics

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA, Circular
  • Drosophila Proteins
  • Heterochromatin
  • RNA, Ribosomal
  • STAT Transcription Factors
  • Transcription Factors
  • heterochromatin-specific nonhistone chromosomal protein HP-1
  • Janus Kinases
  • hop protein, Drosophila