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 B. Niculescu, Daniel R. Salomon, Michael Petrascheck

Research output: Contribution to journalArticle

38 Scopus citations

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 15 2015

ASJC Scopus subject areas

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

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    Rangaraju, S., Solis, G. M., Thompson, R. C., Gomez-Amaro, R. L., Kurian, L., Encalada, S. E., Niculescu, A. B., Salomon, D. R., & 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.08833.001