Tafakori, Tala (2021) Caloric Restriction and the TORC1-Sch9 Nutrient-Signaling Branch Link Chronological Aging to Cellular Quiescence in Yeast Saccharomyces cerevisiae. Masters thesis, Concordia University.
Preview |
Text (application/pdf)
2MBTafakori_Msc_F2021.pdf - Accepted Version |
Abstract
Based on the recent findings of the Titorenko laboratory, I hypothesized that caloric restriction slows the chronological aging of budding yeast Saccharomyces cerevisiae because this geroprotective dietary intervention is integrated into the four processes of a cellular quiescence program. Limitation of calories prolongs yeast longevity by altering the properties of quiescent cells through an intricate network of nutrient-signaling pathways. In addition, I propose that genetic interventions inferring mutations in the Target of Rapamycin Complex 1 (TORC1)-Serine/threonine-protein kinase (Sch9) nutrient signaling branch (such as the tor1Δ and sch9Δ mutations) display longevity-extending phenotypes as a caloric restriction by targeting the processes of the quiescence program. In this study, caloric restriction and the mutant phenotypes of sch9 (in some cells) demonstrated a deceleration of yeast chronological aging by arresting the cell cycle in early G1 and stimulating the development of high-density quiescent cells (process 1), whereas the phenotypes of the tor1 and the sch9 mutants (in some cells) displayed cell cycle arrest in late G1, developing high-density quiescent cells. Caloric restriction promoted an aging-associated conversion of high-density quiescent cells into low-density quiescent cells (process 2), while the phenotypes of the tor1 and the sch9 mutants (in some cells) postponed the conversion of high-density quiescent cells into low-density quiescent cells. Therefore, yeast longevity can be extended by either promoting or decelerating process 2 of the quiescence program. The three interventions displayed a common effect in which they slowed down a fast aging-associated deterioration in clonogenicity of low-density quiescent cells (process 3) and postponed a slow aging-associated decline in clonogenicity of high-density quiescent cells (process 4).
| Divisions: | Concordia University > Faculty of Arts and Science > Biology |
|---|---|
| Item Type: | Thesis (Masters) |
| Authors: | Tafakori, Tala |
| Institution: | Concordia University |
| Degree Name: | M.A. Sc. |
| Program: | Biology |
| Date: | 6 August 2021 |
| Thesis Supervisor(s): | titorenko, vladimir |
| ID Code: | 988888 |
| Deposited By: | Tala Tafakori |
| Deposited On: | 29 Nov 2021 16:41 |
| Last Modified: | 29 Nov 2021 16:41 |
References:
Allen C, Büttner S, Aragon AD, Thomas JA, Meirelles O, Jaetao JE, Benn D, Ruby SW, Veenhuis M, Madeo F, Werner-Washburne M. Isolation of quiescent and non-quiescent cells from yeast stationary-phase cultures. J Cell Biol. 2006; 174:89-100.Aragon AD, Rodriguez AL, Meirelles O, Roy S, Davidson GS, Tapia PH, Allen C, Joe R, Benn D, Werner-Washburne M. Characterization of differentiated quiescent and non-quiescent cells in yeast stationary-phase cultures. Mol Biol Cell. 2008; 19:1271-1280.
Arlia-Ciommo A, Leonov A, Piano A, Svistkova V, Titorenko VI. Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae. Microb Cell. 2014; 1:163-178.
Beach A, Richard VR, Bourque S, Boukh-Viner T, Kyryakov P, Gomez-Perez A, Arlia-Ciommo A, Feldman R, Leonov A, Piano A, Svistkova V, Titorenko VI. Lithocholic bile acid accumulated in yeast mitochondria orchestrates a development of an anti-aging cellular pattern by causing age-related changes in cellular proteome. Cell Cycle. 2015; 14:1643-1656.
Cabib E, Arroyo J. How carbohydrates sculpt cells: chemical control of morphogenesis in the yeast cell wall. Nat Rev Microbiol. 2013; 11:648-655.
Conrad M, Schothorst J, Kankipati HN, Van Zeebroeck G, Rubio-Texeira M, Thevelein JM. Nutrient sensing and signaling in the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev. 2014; 38:254-99.
Davidson GS, Joe RM, Roy S, Meirelles O, Allen CP, Wilson MR, Tapia PH, Manzanilla EE, Dodson AE, Chakraborty S, Carter M, Young S, Edwards B, Sklar L, Werner-Washburne M. The proteomics of quiescent and non-quiescent cell differentiation in yeast stationary-phase cultures. Mol Biol Cell. 2011; 22:988-998.
Deprez MA, Eskes E, Winderickx J, Wilms T. The TORC1-Sch9 pathway as a crucial mediator of chronological lifespan in the yeast Saccharomyces cerevisiae. FEMS Yeast Res. 2018; 18: foy048.
De Virgilio C. The essence of yeast quiescence. FEMS Microbiol Rev. 2012; 36:306-339.
Fraenkel DG. Yeast intermediary metabolism; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, USA, 2011; ISBN 978-0-87969-797-6.
François J, Parrou JL. Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev. 2001; 25:125-145.
Goldberg AA, Bourque SD, Kyryakov P, Gregg C, Boukh-Viner T, Beach A, Burstein MT, Machkalyan G, Richard V, Rampersad S, Cyr D, Milijevic S, Titorenko VI. Effect of calorie restriction on the metabolic history of chronologically aging yeast. Exp Gerontol. 2009; 44:555-571.
Goldberg AA, Richard VR, Kyryakov P, Bourque SD, Beach A, Burstein MT, Glebov A, Koupaki O, Boukh-Viner T, Gregg C, Juneau M, English AM, Thomas DY, Titorenko VI. Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes. Aging (Albany NY). 2010; 2:393-414.
Gladyshev VN. The origin of aging: imperfectness-driven non-random damage defines the aging process and control of lifespan. Trends Genet. 2013; 29:506-512.
Giorgio M, Trinei M, Migliaccio E, Pelicci PG. Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol. 2007; 8:722-728.
Gulli J, Cook E, Kroll E, Rosebrock A, Caudy A, Rosenzweig F. Diverse conditions support near-zero growth in yeast: Implications for the study of cell lifespan. Microb Cell. 2019; 6:397-413.
He K, Gkioxari G, Dollar P, Girshes R. Mask R-CNN. IEEE Trans Pattern Anal Mach Intell. 2020; 42:386-397.
Herker E, Jungwirth H, Lehmann KA, Maldener C, Fröhlich KU, Wissing S, Büttner S, Fehr M, Sigrist S, Madeo F. Chronological aging leads to apoptosis in yeast. J Cell Biol. 2004; 164:501-507.
Kaeberlein M, Burtner CR, Kennedy BK. Recent developments in yeast aging. PLoS Genet. 2007; 3: e84.
Kyryakov P, Beach A, Richard VR, Burstein MT, Leonov A, Levy S, Titorenko VI. Caloric restriction extends yeast chronological lifespan by altering a pattern of age-related changes in trehalose concentration. Front Physiol. 2012; 3: 256.
Leonov A, Feldman R, Piano A, Arlia-Ciommo A, Lutchman V, Ahmadi M, Elsaser S, Fakim H, Heshmati-Moghaddam M, Hussain A, Orfali S, Rajen H, Roofigari-Esfahani N, Rosanelli L, Titorenko VI. Caloric restriction extends yeast chronological lifespan via a mechanism linking cellular aging to cell cycle regulation, maintenance of a quiescent state, entry into a non-quiescent state and survival in the non-quiescent state. Oncotarget. 2017; 8:69328-69350.
Leonov A, Titorenko VI. A network of interorganellar communications underlies cellular aging. IUBMB Life. 2013; 65:665-674.
Longo VD. Mutations in signal transduction proteins increase stress resistance and longevity in yeast, nematodes, fruit flies, and mammalian neuronal cells. Neurobiol Aging. 1999; 20: 479-486.
Longo VD, Shadel GS, Kaeberlein M, Kennedy B. Replicative and chronological aging in Saccharomyces cerevisiae. Cell Metab. 2012; 16:18-31.
Madeo F, Carmona-Gutierrez D, Hofer SJ, Kroemer G. Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential. Cell Metab. 2019; 29:592-610.
Lu AX, Zarin T, Hsu IS, Moses AM. YeastSpotter: accurate and parameter-free web segmentation for microscopy images of yeast cells. Bioinformatics. 2019; 35:4525-4527.
Miles S, Li L, Davison J, Breeden LL. Xbp1 directs global repression of budding yeast transcription during the transition to quiescence and is important for the longevity and reversibility of the quiescent state. PLoS Genet. 2013; 9: e1003854.
Miles S, Li LH, Melville Z, Breeden LL. Ssd1 and the cell wall integrity pathway promote entry, maintenance, and recovery from quiescence in budding yeast. Mol Biol Cell. 2019; 30:2205-2217.
Mitrofanova D, Dakik P, McAuley M, Medkour Y, Mohammad K, Titorenko VI. Lipid metabolism and transport define longevity of the yeast Saccharomyces cerevisiae. Front Biosci (Landmark Ed). 2018; 23:1166-1194.
Ogrodnik M, Salmonowicz H, Gladyshev VN. Integrating cellular senescence with the concept of damage accumulation in aging: Relevance for clearance of senescent cells. Aging Cell. 2019; 18: e12841.
Palková Z, Wilkinson D, Váchová L. Aging and differentiation in yeast populations: elders with different properties and functions. FEMS Yeast Res. 2014; 14:96-108.
Powers RW 3rd, Kaeberlein M, Caldwell SD, Kennedy BK, and Fields S. Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev. 2006; 20: 174-184.
Richard VR, Beach A, Piano A, Leonov A, Feldman R, Burstein MT, Kyryakov P, Gomez-Perez A, Arlia-Ciommo A, Baptista S, Campbell C, Goncharov D, Pannu S, Patrinos D, Sadri B, Svistkova V, Victor A, Titorenko VI. Mechanism of liponecrosis, a distinct mode of programmed cell death. Cell Cycle. 2014; 13):3707-3726.
Sagot I, Laporte D. The cell biology of quiescent yeast - a diversity of individual scenarios. J Cell Sci. 2019; 132: jcs213025.
Shashkova S, Welkenhuysen N, Hohmann S. Molecular communication: crosstalk between the Snf1 and other signaling pathways. FEMS Yeast Res. 2015; 15: fov026.
Sheibani S, Richard VR, Beach A, Leonov A, Feldman R, Mattie S, Khelghatybana L, Piano A, Greenwood M, Vali H, Titorenko VI. Macromitophagy, neutral lipids synthesis, and peroxisomal fatty acid oxidation protect yeast from “liponecrosis”, a previously unknown form of programmed cell death. Cell Cycle. 2014; 13:138-147.
Sinclair DA. Toward a unified theory of caloric restriction and longevity regulation. Mech Ageing Dev. 2005; 126:987-1002.
Smets B, Ghillebert R, De Snijder P, Binda M, Swinnen E, De Virgilio C, Winderickx J. Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae. Curr Genet. 2010; 56:1-32.
Swinnen E, Ghillebert R, Wilms T, Winderickx J. Molecular mechanisms linking the evolutionary conserved TORC1-Sch9 nutrient signalling branch to lifespan regulation in Saccharomyces cerevisiae. FEMS Yeast Res. 2014; 14:17-32.
Werner-Washburne M, Roy S, Davidson GS. Aging and the survival of quiescent and non-quiescent cells in yeast stationary-phase cultures. Subcell Biochem. 2012; 57:123-143.
Zhang L, Winkler S, Schlottmann FP, Kohlbacher O, Elias JE, Skotheim JM, Ewald JC. Multiple Layers of Phospho-Regulation Coordinate Metabolism and the Cell Cycle in Budding Yeast. Front Cell Dev Biol. 2019;7: 338.
All items in Spectrum are protected by copyright, with all rights reserved. The use of items is governed by Spectrum's terms of access.
Repository Staff Only: item control page
Download Statistics
Download Statistics