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 |