RRC ID 53434
著者 Rangaraju S, Solis GM, Thompson RC, Gomez-Amaro RL, Kurian L, Encalada SE, Niculescu AB 3rd, Salomon DR, Petrascheck M.
タイトル Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality.
ジャーナル Elife
Abstract Longevity mechanisms increase lifespan by counteracting the effects of aging. However, whether longevity mechanisms counteract the effects of aging continually throughout life, or whether they act during specific periods of life, preventing changes that precede mortality is unclear. Here, we uncover transcriptional drift, a phenomenon that describes how aging causes genes within functional groups to change expression in opposing directions. These changes cause a transcriptome-wide loss in mRNA stoichiometry and loss of co-expression patterns in aging animals, as compared to young adults. Using Caenorhabditis elegans as a model, we show that extending lifespan by inhibiting serotonergic signals by the antidepressant mianserin attenuates transcriptional drift, allowing the preservation of a younger transcriptome into an older age. Our data are consistent with a model in which inhibition of serotonergic signals slows age-dependent physiological decline and the associated rise in mortality levels exclusively in young adults, thereby postponing the onset of major mortality.
巻・号 4
ページ e08833
公開日 2015-12-1
DOI 10.7554/eLife.08833
PII e08833
PMID 26623667
PMC PMC4720515
MeSH Aging* Animals Caenorhabditis elegans / drug effects* Caenorhabditis elegans / physiology* Gene Expression Profiling Gene Expression Regulation / drug effects* Longevity / drug effects* Mianserin / administration & dosage Serotonin Antagonists / administration & dosage* Transcription, Genetic*
IF 7.08
引用数 36
リソース情報
線虫 tm2647 tm2654 tm2146 tm1325