Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Rangaraju, Sunitha, Solis, Gregory M, Thompson, Ryan C, Gomez-Amaro, Rafael L, Kurian, Leo, Encalada, Sandra E, Niculescu, Alexander B, Salomon, Daniel R, Petrascheck, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720515/
https://www.ncbi.nlm.nih.gov/pubmed/26623667
http://dx.doi.org/10.7554/eLife.08833
_version_ 1782411096934580224
author Rangaraju, Sunitha
Solis, Gregory M
Thompson, Ryan C
Gomez-Amaro, Rafael L
Kurian, Leo
Encalada, Sandra E
Niculescu, Alexander B
Salomon, Daniel R
Petrascheck, Michael
author_facet Rangaraju, Sunitha
Solis, Gregory M
Thompson, Ryan C
Gomez-Amaro, Rafael L
Kurian, Leo
Encalada, Sandra E
Niculescu, Alexander B
Salomon, Daniel R
Petrascheck, Michael
author_sort Rangaraju, Sunitha
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.08833.001
format Online
Article
Text
id pubmed-4720515
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-47205152016-01-21 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 B Salomon, Daniel R Petrascheck, Michael eLife Computational and Systems Biology 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. DOI: http://dx.doi.org/10.7554/eLife.08833.001 eLife Sciences Publications, Ltd 2015-12-01 /pmc/articles/PMC4720515/ /pubmed/26623667 http://dx.doi.org/10.7554/eLife.08833 Text en © 2015, Rangaraju et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Rangaraju, Sunitha
Solis, Gregory M
Thompson, Ryan C
Gomez-Amaro, Rafael L
Kurian, Leo
Encalada, Sandra E
Niculescu, Alexander B
Salomon, Daniel R
Petrascheck, Michael
Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality
title Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality
title_full Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality
title_fullStr Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality
title_full_unstemmed Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality
title_short Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality
title_sort suppression of transcriptional drift extends c. elegans lifespan by postponing the onset of mortality
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720515/
https://www.ncbi.nlm.nih.gov/pubmed/26623667
http://dx.doi.org/10.7554/eLife.08833
work_keys_str_mv AT rangarajusunitha suppressionoftranscriptionaldriftextendsceleganslifespanbypostponingtheonsetofmortality
AT solisgregorym suppressionoftranscriptionaldriftextendsceleganslifespanbypostponingtheonsetofmortality
AT thompsonryanc suppressionoftranscriptionaldriftextendsceleganslifespanbypostponingtheonsetofmortality
AT gomezamarorafaell suppressionoftranscriptionaldriftextendsceleganslifespanbypostponingtheonsetofmortality
AT kurianleo suppressionoftranscriptionaldriftextendsceleganslifespanbypostponingtheonsetofmortality
AT encaladasandrae suppressionoftranscriptionaldriftextendsceleganslifespanbypostponingtheonsetofmortality
AT niculescualexanderb suppressionoftranscriptionaldriftextendsceleganslifespanbypostponingtheonsetofmortality
AT salomondanielr suppressionoftranscriptionaldriftextendsceleganslifespanbypostponingtheonsetofmortality
AT petrascheckmichael suppressionoftranscriptionaldriftextendsceleganslifespanbypostponingtheonsetofmortality