title: Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis.
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.
authors.affiliation: Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Larson
authors.forename: Shian-Jang
authors.initials: SJ
authors.lastname: Yan
authors.forename: Amy
authors.initials: A
authors.lastname: Tsurumi
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Kriti
authors.initials: K
authors.lastname: Gaur
authors.forename: Dongdong
authors.initials: D
authors.lastname: Guo
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Eickbush
authors.forename: Willis X
authors.initials: WX
authors.lastname: Li
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D002466:Cell Nucleolus / Q000235:genetics; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004270:DNA, Circular / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000235:genetics; D042822:Genomic Instability; D006570:Heterochromatin / Q000235:genetics*; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D009132:Muscles / Q000502:physiology; D012335:RNA, Ribosomal / Q000096:biosynthesis* / Q000235:genetics; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004270:DNA, Circular; D029721:Drosophila Proteins; D006570:Heterochromatin; D012335:RNA, Ribosomal; D050791:STAT Transcription Factors; D014157:Transcription Factors; D000090266:Chromobox Protein Homolog 5; D053612:Janus Kinases; C085845:hop protein, Drosophila