Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York, USA.
PLoS Genet. 2012 Jan;8(1):e1002473. doi: 10.1371/journal.pgen.1002473. Epub 2012 Jan 26.
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.
生物体的衰老受到多种内在和外在因素的影响，异染色质的丢失被认为是衰老的原因之一。然而，异染色质在动物衰老中的作用一直存在争议。在这里，我们表明异染色质的形成可以延长果蝇的寿命并控制核糖体 RNA 的合成。异染色质水平降低的动物寿命明显缩短，而增加异染色质则延长寿命。寿命的变化与肌肉完整性的变化有关。此外，我们还表明，随着正常衰老，异染色质水平会降低，并且异染色质的形成对于 rRNA 转录的沉默是必需的。先前已经表明，酵母衰老与表观遗传沉默的丧失以及 rDNA 位点的不稳定性丧失有关。综上所述，这些结果表明，基因组稳定性的表观遗传保存，特别是在 rDNA 位点，以及对不必要的 rRNA 合成的抑制，可能是延长寿命的一种进化保守机制。
