Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan

Research output: Contribution to journalArticle

Zheng Hu, Bo Xia, Spike D.L. Postnikoff, Zih Jie Shen, Alin S. Tomoiaga, Troy A. Harkness, Ja Hwan Seol, Wei Li, Kaifu Chen, Jessica K. Tyler

Translational efficiency correlates with longevity, yet its role in lifespan determination remains unclear. Using ribosome profiling, translation efficiency is globally reduced during replicative aging in budding yeast by at least two mechanisms: Firstly, Ssd1 is induced during aging, sequestering mRNAs to P-bodies. Furthermore, Ssd1 overexpression in young cells reduced translation and extended lifespan, while loss of Ssd1 reduced the translational deficit of old cells and shortened lifespan. Secondly, phosphorylation of eIF2α, mediated by the stress kinase Gcn2, was elevated in old cells, contributing to the global reduction in translation without detectable induction of the downstream Gcn4 transcriptional activator. tRNA overexpression activated Gcn2 in young cells and extended lifespan in a manner dependent on Gcn4. Moreover, overexpression of Gcn4 sufficed to extend lifespan in an autophagy-dependent manner in the absence of changes in global translation, indicating that Gcn4-mediated autophagy induction is the ultimate downstream target of activated Gcn2, to extend lifespan.

Original languageEnglish (US)
Article numbere35551
JournaleLife
Volume7
DOIs
StatePublished - Aug 17 2018

PMID: 30117416

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Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan. / Hu, Zheng; Xia, Bo; Postnikoff, Spike D.L.; Shen, Zih Jie; Tomoiaga, Alin S.; Harkness, Troy A.; Seol, Ja Hwan; Li, Wei; Chen, Kaifu; Tyler, Jessica K.

In: eLife, Vol. 7, e35551, 17.08.2018.

Research output: Contribution to journalArticle

Harvard

Hu, Z, Xia, B, Postnikoff, SDL, Shen, ZJ, Tomoiaga, AS, Harkness, TA, Seol, JH, Li, W, Chen, K & Tyler, JK 2018, 'Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan' eLife, vol. 7, e35551. https://doi.org/10.7554/eLife.35551

APA

Hu, Z., Xia, B., Postnikoff, S. D. L., Shen, Z. J., Tomoiaga, A. S., Harkness, T. A., ... Tyler, J. K. (2018). Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan. eLife, 7, [e35551]. https://doi.org/10.7554/eLife.35551

Vancouver

Hu Z, Xia B, Postnikoff SDL, Shen ZJ, Tomoiaga AS, Harkness TA et al. Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan. eLife. 2018 Aug 17;7. e35551. https://doi.org/10.7554/eLife.35551

Author

Hu, Zheng ; Xia, Bo ; Postnikoff, Spike D.L. ; Shen, Zih Jie ; Tomoiaga, Alin S. ; Harkness, Troy A. ; Seol, Ja Hwan ; Li, Wei ; Chen, Kaifu ; Tyler, Jessica K. / Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan. In: eLife. 2018 ; Vol. 7.

BibTeX

@article{e5d2b762e2804d6a8c9901b2bc8d0771,
title = "Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan",
abstract = "Translational efficiency correlates with longevity, yet its role in lifespan determination remains unclear. Using ribosome profiling, translation efficiency is globally reduced during replicative aging in budding yeast by at least two mechanisms: Firstly, Ssd1 is induced during aging, sequestering mRNAs to P-bodies. Furthermore, Ssd1 overexpression in young cells reduced translation and extended lifespan, while loss of Ssd1 reduced the translational deficit of old cells and shortened lifespan. Secondly, phosphorylation of eIF2α, mediated by the stress kinase Gcn2, was elevated in old cells, contributing to the global reduction in translation without detectable induction of the downstream Gcn4 transcriptional activator. tRNA overexpression activated Gcn2 in young cells and extended lifespan in a manner dependent on Gcn4. Moreover, overexpression of Gcn4 sufficed to extend lifespan in an autophagy-dependent manner in the absence of changes in global translation, indicating that Gcn4-mediated autophagy induction is the ultimate downstream target of activated Gcn2, to extend lifespan.",
author = "Zheng Hu and Bo Xia and Postnikoff, {Spike D.L.} and Shen, {Zih Jie} and Tomoiaga, {Alin S.} and Harkness, {Troy A.} and Seol, {Ja Hwan} and Wei Li and Kaifu Chen and Tyler, {Jessica K.}",
year = "2018",
month = "8",
day = "17",
doi = "10.7554/eLife.35551",
language = "English (US)",
volume = "7",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

RIS

TY - JOUR

T1 - Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast while their activation extends lifespan

AU - Hu, Zheng

AU - Xia, Bo

AU - Postnikoff, Spike D.L.

AU - Shen, Zih Jie

AU - Tomoiaga, Alin S.

AU - Harkness, Troy A.

AU - Seol, Ja Hwan

AU - Li, Wei

AU - Chen, Kaifu

AU - Tyler, Jessica K.

PY - 2018/8/17

Y1 - 2018/8/17

N2 - Translational efficiency correlates with longevity, yet its role in lifespan determination remains unclear. Using ribosome profiling, translation efficiency is globally reduced during replicative aging in budding yeast by at least two mechanisms: Firstly, Ssd1 is induced during aging, sequestering mRNAs to P-bodies. Furthermore, Ssd1 overexpression in young cells reduced translation and extended lifespan, while loss of Ssd1 reduced the translational deficit of old cells and shortened lifespan. Secondly, phosphorylation of eIF2α, mediated by the stress kinase Gcn2, was elevated in old cells, contributing to the global reduction in translation without detectable induction of the downstream Gcn4 transcriptional activator. tRNA overexpression activated Gcn2 in young cells and extended lifespan in a manner dependent on Gcn4. Moreover, overexpression of Gcn4 sufficed to extend lifespan in an autophagy-dependent manner in the absence of changes in global translation, indicating that Gcn4-mediated autophagy induction is the ultimate downstream target of activated Gcn2, to extend lifespan.

AB - Translational efficiency correlates with longevity, yet its role in lifespan determination remains unclear. Using ribosome profiling, translation efficiency is globally reduced during replicative aging in budding yeast by at least two mechanisms: Firstly, Ssd1 is induced during aging, sequestering mRNAs to P-bodies. Furthermore, Ssd1 overexpression in young cells reduced translation and extended lifespan, while loss of Ssd1 reduced the translational deficit of old cells and shortened lifespan. Secondly, phosphorylation of eIF2α, mediated by the stress kinase Gcn2, was elevated in old cells, contributing to the global reduction in translation without detectable induction of the downstream Gcn4 transcriptional activator. tRNA overexpression activated Gcn2 in young cells and extended lifespan in a manner dependent on Gcn4. Moreover, overexpression of Gcn4 sufficed to extend lifespan in an autophagy-dependent manner in the absence of changes in global translation, indicating that Gcn4-mediated autophagy induction is the ultimate downstream target of activated Gcn2, to extend lifespan.

UR - http://www.scopus.com/inward/record.url?scp=85053868343&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053868343&partnerID=8YFLogxK

U2 - 10.7554/eLife.35551

DO - 10.7554/eLife.35551

M3 - Article

VL - 7

JO - eLife

T2 - eLife

JF - eLife

SN - 2050-084X

M1 - e35551

ER -

ID: 40991295