Molecular mechanisms underlying genotype‐dependent responses to dietary restriction
Open accessAbstract
Summary: Dietary restriction ( DR ) increases lifespan and attenuates age‐related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here, we describe a large‐scale effort to define molecular mechanisms that underlie genotype‐specific responses to DR . The effect of DR on lifespan was determined for 166 single gene deletion strains in Saccharomyces cerevisiae . Resulting changes in mean lifespan ranged from a reduction of 79% to an increase of 103%. Vacuolar p H homeostasis, superoxide dismutase activity, and mitochondrial proteostasis were found to be strong determinants of the response to DR . Proteomic analysis of cells deficient in prohibitins revealed induction of a mitochondrial unfolded protein response (mt UPR ), which has not previously been described in yeast. Mitochondrial proteotoxic stress in prohibitin mutants was suppressed by DR via reduced cytoplasmic m RNA translation. A similar relationship between prohibitins, the mt UPR , and longevity was also observed in C aenorhabditis elegans . These observations define conserved molecular processes that underlie genotype‐dependent effects of DR that may be important modulators of DR in higher organisms.
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Even among highly genetically similar strains of yeast or mice, dietary restriction is equally likely to shorten lifespan as to extend lifespan.
“Even among highly genetically similar strains of yeast or mice, dietary restriction is equally likely to shorten lifespan as to extend lifespan.76,77,78”
From Asynchronous, contagious and digital aging (2021) · cites this paper as [76]
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- Authors
- Schleit, J., Johnson, S. C., Bennett, C. F., Simko, M., Trongtham, N., Castanza, A., Hsieh, E. J., Moller, R. M., Wasko, B. M., Delaney, J. R., Sutphin, G. L., Carr, D., Murakami, C. J., Tocchi, A., Xian, B., Chen, W., Yu, T., Goswami, S., Higgins, S., Jeong, K., Kim, J. R., Klum, S., Liao, E., Lin, M. S., Lo, W., Miller, H., Olsen, B., Peng, Z. J., Pollard, T., Pradeep, P., Pruett, D., Rai, D., Ros, V., Singh, M., Spector, B. L., Wende, H. V., An, E. H., Fletcher, M., Jelic, M., Rabinovitch, P. S., MacCoss, M. J., Han, J. J., Kennedy, B. K., & Kaeberlein, M.
- Affiliations
- University of Washington (US)
- Chinese Academy of Sciences (CN)
- Department of Pathology University of Washington Seattle WA USA
- Buck Institute for Research on Aging (US)
- Guangdong Medical College (CN)
- Corresponding author
- Kaeberlein, Matt
- ORCID
- Johnson, Simon C.
- Bennett, Christopher F.
- Castanza, Anthony
- Wasko, Brian M.
- Delaney, Joe R.
- Sutphin, George L.
- Xian, Bo
- Chen, Weiyang
- Yu, Tao
- Miller, Hillary
- Pruett, Dillon
- Spector, Benjamin L.
- Wende, Helen Vander
- Fletcher, Marissa
- Jelic, Monika
- Rabinovitch, Peter S.
- MacCoss, Michael J.
- Han, Jing‐Dong J.
- Kennedy, Brian K.
- Kaeberlein, Matt
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2013-08-11
- Volume
- 12
- Issue
- 6
- Pages
- 1050-1061
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC3838465
- OpenAlex
- W2075612822
- Cited by
- 159
- References
- 47
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 16 · 2023: 7 · 2022: 2 · 2021: 13 · 2020: 20 · 2019: 9 · 2018: 13 · 2017: 8 · 2016: 9 · 2015: 21 · 2014: 25 · 2013: 7
- FWCI
- 7.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (T32AG000057, P01AG001751, R01AG039390, P30AG013280)
- National Institute of General Medical Sciences (P41GM103533, T32GM007270)
- National Institute of Environmental Health Sciences (T32ES007032)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- dietary restriction, lifespan, genotype-dependent response, Saccharomyces cerevisiae, Caenorhabditis elegans, prohibitin, mitochondrial unfolded protein response, mitochondrial proteostasis, superoxide dismutase, longevity
- MeSH terms
- Prohibitins, Aerobiosis, Animals, Autophagy, Diet, Genotype, Saccharomyces cerevisiae, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Caloric Restriction, Unfolded Protein Response
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