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A quantitative yeast aging proteomics analysis reveals novel aging regulators

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Abstract

Calorie restriction (CR) is the most robust longevity intervention, extending lifespan from yeast to mammals. Numerous conserved pathways regulating aging and mediating CR have been identified; however, the overall proteomic changes during these conditions remain largely unexplored. We compared proteomes between young and replicatively aged yeast cells under normal and CR conditions using the Stable-Isotope Labeling by Amino acids in Cell culture (SILAC) quantitative proteomics and discovered distinct signatures in the aging proteome. We found remarkable proteomic similarities between aged and CR cells, including induction of stress response pathways, providing evidence that CR pathways are engaged in aged cells. These observations also uncovered aberrant changes in mitochondria membrane proteins as well as a proteolytic cellular state in old cells. These proteomics analyses help identify potential genes and pathways that have causal effects on longevity.

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Availability of data and material

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD018917. The RNA-seq data have been deposited to SRA under accession number PRJNA715646.

All experimental materials generated by this study are available upon request.

Code availability

Not applicable.

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Acknowledgements

We would like to thank Dr. Shelley Berger (UPenn) for her advice on this project. We also thank Dr. Michiel Vermeulen and Pascal Jansen (The Radboud University Medical Centre) for providing mass spectrometry analysis service.

Funding

This study was supported by NIH grants K99/R00AG037646, R56AG049714, R01AG052507, and R41/R42AG058368 to WD, CPRIT Scholar award R1306 to WD, Welch Foundation grant Q-1986–20190330 to WD, NSF award #1720215, #1761839, and internal support of the University of Tennessee at Chattanooga to HQ.

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Author notes

  1. Yu Sun and Ruofan Yu contributioned equally to the study.

Authors and Affiliations

  1. Huffington Center On Aging and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA

    Yu Sun & Weiwei Dang

  2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Ruofan Yu

  3. Department of Computer Science and Engineering, Department of Biology, Geology and Environmental Science, SimCenter, The University of Tennessee At Chattanooga, Chattanooga, TN, 37403, USA

    Hao-Bo Guo & Hong Qin

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  1. Yu Sun
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Contributions

Conceptualization, YS and WD; data curation, YS, RY, and WD; formal analysis, YS, RY, HG, HQ, and WD; funding acquisition, HQ, and WD; investigation, YS, RY, and HG; methodology, YS, RY, HG, and WD; project administration, YS and WD; resources, HQ, and WD; supervision, WD; validation, YS, RY and WD; writing — original draft, YS, RY and WD; writing — review and editing, YS, RY, HQ, and WD.

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Correspondence to Weiwei Dang.

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Sun, Y., Yu, R., Guo, HB. et al. A quantitative yeast aging proteomics analysis reveals novel aging regulators. GeroScience 43, 2573–2593 (2021). https://doi.org/10.1007/s11357-021-00412-3

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  • DOI: https://doi.org/10.1007/s11357-021-00412-3

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