heterochromatin formation promotes longevity and represses ribosomal rna synthesis异染色质形成促进长寿和压制核糖体rna合成.pdfVIP

Heterochromatin Formation Promotes Longevity and Represses Ribosomal RNA Synthesis 1. 1,2. 1. 1. 3 1 Kimberly Larson , Shian-Jang Yan , Amy Tsurumi , Jacqueline Liu , Jun Zhou , Kriti Gaur , 1 3 1,2 Dongdong Guo , Thomas H. Eickbush , Willis X. Li * 1 Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York, United States of America, 2 Department of Medicine, University of California San Diego, La Jolla, California, United States of America, 3 Department of Biology, University of Rochester, Rochester, New York, United States of America 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