Report
pH neutralization protects against reduction in replicative lifespan following chronological aging in yeast
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Volume 11, Issue 16 August 15, 2012
Pages 3087 - 3096
http://dx.doi.org/10.4161/cc.21465
Keywords: chronological lifespan, longevity, replication stress, replicative lifespan, yeast
Authors: Christopher Murakami, Joe R. Delaney, Annie Chou, Daniel Carr, Jennifer Schleit, George L. Sutphin, Elroy H. An, Anthony S. Castanza, Marissa Fletcher, Sarani Goswami, Sean Higgins, Mollie Holmberg, Jessica Hui, Monika Jelic, Ki-Soo Jeong, Jin R. Kim, Shannon Klum, Eric Liao, Michael S. Lin, Winston Lo, Hillary Miller, Richard Moller, Zhao J. Peng, Tom Pollard, Prarthana Pradeep, Dillon Pruett, Dilreet Rai, Vanessa Ros, Alex Schuster, Minnie Singh, Benjamin L. Spector, Helen Vander Wende, Adrienne M. Wang, Brian M. Wasko, Brady Olsen and Matt Kaeberlein
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- Christopher Murakami
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Department of Pathology; University of Washington; Seattle, WA USA
These authors contributed equally to this work.
- Joe R. Delaney
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Department of Pathology; University of Washington; Seattle, WA USA; Molecular and Cellular Biology Program; University of Washington; Seattle, WA USA
These authors contributed equally to this work.
- Annie Chou
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Department of Pathology; University of Washington; Seattle, WA USA
- Daniel Carr
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Department of Pathology; University of Washington; Seattle, WA USA
- Jennifer Schleit
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Department of Pathology; University of Washington; Seattle, WA USA
- George L. Sutphin
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Department of Pathology; University of Washington; Seattle, WA USA; Molecular and Cellular Biology Program; University of Washington; Seattle, WA USA
- Elroy H. An
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Department of Pathology; University of Washington; Seattle, WA USA
- Anthony S. Castanza
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Department of Pathology; University of Washington; Seattle, WA USA
- Marissa Fletcher
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Department of Pathology; University of Washington; Seattle, WA USA
- Sarani Goswami
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Department of Pathology; University of Washington; Seattle, WA USA
- Sean Higgins
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Department of Pathology; University of Washington; Seattle, WA USA
- Mollie Holmberg
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Department of Pathology; University of Washington; Seattle, WA USA
- Jessica Hui
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Department of Pathology; University of Washington; Seattle, WA USA
- Monika Jelic
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Department of Pathology; University of Washington; Seattle, WA USA
- Ki-Soo Jeong
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Department of Pathology; University of Washington; Seattle, WA USA
- Jin R. Kim
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Department of Pathology; University of Washington; Seattle, WA USA
- Shannon Klum
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Department of Pathology; University of Washington; Seattle, WA USA
- Eric Liao
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Department of Pathology; University of Washington; Seattle, WA USA
- Michael S. Lin
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Department of Pathology; University of Washington; Seattle, WA USA
- Winston Lo
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Department of Pathology; University of Washington; Seattle, WA USA
- Hillary Miller
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Department of Pathology; University of Washington; Seattle, WA USA
- Richard Moller
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Department of Pathology; University of Washington; Seattle, WA USA
- Zhao J. Peng
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Department of Pathology; University of Washington; Seattle, WA USA
- Tom Pollard
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Department of Pathology; University of Washington; Seattle, WA USA
- Prarthana Pradeep
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Department of Pathology; University of Washington; Seattle, WA USA
- Dillon Pruett
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Department of Pathology; University of Washington; Seattle, WA USA
- Dilreet Rai
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Department of Pathology; University of Washington; Seattle, WA USA
- Vanessa Ros
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Department of Pathology; University of Washington; Seattle, WA USA
- Alex Schuster
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Department of Pathology; University of Washington; Seattle, WA USA
- Minnie Singh
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Department of Pathology; University of Washington; Seattle, WA USA
- Benjamin L. Spector
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Department of Pathology; University of Washington; Seattle, WA USA
- Helen Vander Wende
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Department of Pathology; University of Washington; Seattle, WA USA
- Adrienne M. Wang
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Department of Pathology; University of Washington; Seattle, WA USA
- Brian M. Wasko
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Department of Pathology; University of Washington; Seattle, WA USA
- Brady Olsen
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Department of Pathology; University of Washington; Seattle, WA USA
- Matt Kaeberlein
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Corresponding author: kaeber@uw.edu
Department of Pathology; University of Washington; Seattle, WA USA; Institute of Aging Research; Guangdong Medical College; Dongguan, China
Abstract:
Chronological and replicative aging have been studied in yeast as alternative paradigms for post-mitotic and mitotic aging, respectively. It has been known for more than a decade that cells of the S288C background aged chronologically in rich medium have reduced replicative lifespan relative to chronologically young cells. Here we report replication of this observation in the diploid BY4743 strain background. We further show that the reduction in replicative lifespan from chronological aging is accelerated when cells are chronologically aged under standard conditions in synthetic complete medium rather than rich medium. The loss of replicative potential with chronological age is attenuated by buffering the pH of the chronological aging medium to 6.0, an intervention that we have previously shown can extend chronological lifespan. These data demonstrate that extracellular acidification of the culture medium can cause intracellular damage in the chronologically aging population that is asymmetrically segregated by the mother cell to limit subsequent replicative lifespan.
Received: July 11, 2012; Accepted: July 12, 2012; Published Online: August 8, 2012
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