Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality

Sunitha Rangaraju, Gregory M. Solis, Ryan C. Thompson, Rafael L. Gomez-Amaro, Leo Kurian, Sandra E. Encalada, Alexander Niculescu, Daniel R. Salomon, Michael Petrascheck

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere08833
JournaleLife
Volume4
Issue numberDecember2015
DOIs
StatePublished - Dec 1 2015

Fingerprint

Aging of materials
Transcriptome
Mortality
Young Adult
Mianserin
Caenorhabditis elegans
Antidepressive Agents
Stoichiometry
Functional groups
Messenger RNA
Animals
Genes
Direction compound

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Rangaraju, S., Solis, G. M., Thompson, R. C., Gomez-Amaro, R. L., Kurian, L., Encalada, S. E., ... Petrascheck, M. (2015). Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality. eLife, 4(December2015), [e08833]. https://doi.org/10.7554/eLife.08833

Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality. / Rangaraju, Sunitha; Solis, Gregory M.; Thompson, Ryan C.; Gomez-Amaro, Rafael L.; Kurian, Leo; Encalada, Sandra E.; Niculescu, Alexander; Salomon, Daniel R.; Petrascheck, Michael.

In: eLife, Vol. 4, No. December2015, e08833, 01.12.2015.

Research output: Contribution to journalArticle

Rangaraju, S, Solis, GM, Thompson, RC, Gomez-Amaro, RL, Kurian, L, Encalada, SE, Niculescu, A, Salomon, DR & Petrascheck, M 2015, 'Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality', eLife, vol. 4, no. December2015, e08833. https://doi.org/10.7554/eLife.08833
Rangaraju S, Solis GM, Thompson RC, Gomez-Amaro RL, Kurian L, Encalada SE et al. Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality. eLife. 2015 Dec 1;4(December2015). e08833. https://doi.org/10.7554/eLife.08833
Rangaraju, Sunitha ; Solis, Gregory M. ; Thompson, Ryan C. ; Gomez-Amaro, Rafael L. ; Kurian, Leo ; Encalada, Sandra E. ; Niculescu, Alexander ; Salomon, Daniel R. ; Petrascheck, Michael. / Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality. In: eLife. 2015 ; Vol. 4, No. December2015.
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