Login | Register

The Effects of Six Potent Age-Delaying Plant Extracts on the Cellular Lipidome of Saccharomyces cerevisiae


The Effects of Six Potent Age-Delaying Plant Extracts on the Cellular Lipidome of Saccharomyces cerevisiae

Desjardins, Christyna Elyse (2023) The Effects of Six Potent Age-Delaying Plant Extracts on the Cellular Lipidome of Saccharomyces cerevisiae. Masters thesis, Concordia University.

[thumbnail of The Effects of Six Potent Age Delaying Plant Extracts on the Cellular Lipidome of Saccharomyces cerevisiae.pdf]
Text (application/pdf)
The Effects of Six Potent Age Delaying Plant Extracts on the Cellular Lipidome of Saccharomyces cerevisiae.pdf - Accepted Version
Available under License Spectrum Terms of Access.


The objective of this study is to better understand the involvement of anti-aging plant extracts on the lipidome. My hypothesis was that some of the previously studied twenty-one age-delaying plant extracts extend aging by altering lipid and free fatty acid synthesis and/or metabolism. To test this hypothesis, my thesis analyzed the lipidome of Saccharomyces cerevisiae after treatment with Plant Extract 4, 6, 12, 21, 26, and 39, all of which have been previously shown to delay aging. The lipids were extracted from the treated and untreated S. cerevisiae and analyzed by a Mass Spectrometer. My results revealed that the six plant extracts enhanced the level of certain lipids and significantly decreased the level of free fatty acids. Similar results were obtained in a previous study done on caloric restriction, where caloric restriction enhanced the level of lipids and decreased the level of free fatty acids. Notably, while some lipids increased or decreased, during both caloric restriction and plant extract exposure, there was a general trend for free fatty acids to decrease, supporting that they may have a more consistent role in aging compared to lipids.

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Thesis (Masters)
Authors:Desjardins, Christyna Elyse
Institution:Concordia University
Degree Name:M.A. Sc.
Date:August 2023
Thesis Supervisor(s):Titorenko, Vladimir and Zerges, William
ID Code:992995
Deposited By: Christyna Elyse Desjardins
Deposited On:14 Nov 2023 19:19
Last Modified:14 Nov 2023 19:19



1. Fontana L, Partridge L, Longo VD (2010) Dietary Restriction, Growth Factors and Aging: from yeast to humans. Science 328: 321–326.
2. Weinert BT, Timiras PS (2003) Invited review: Theories of aging. J Appl Physiol Bethesda Md 1985 95: 1706–1716.
3. Roser M, Ortiz-Ospina E, Ritchie H (2013) Life Expectancy. Our World Data.
4. OECD (2015) The growing human and financial cost of dementia: The case for policy action, Paris, OECD.
5. Longo VD, Shadel GS, Kaeberlein M, et al. (2012) Replicative and chronological aging in Saccharomyces cerevisiae. Cell Metab 16: 18–31.
6. Kaeberlein M (2010) Lessons on longevity from budding yeast. Nature 464: 513–519.
7. Váchová L, Cáp M, Palková Z (2012) Yeast colonies: a model for studies of aging, environmental adaptation, and longevity. Oxid Med Cell Longev 2012: 601836.
8. Fontana L, Partridge L, Longo VD (2010) Extending healthy life span--from yeast to humans. Science 328: 321–326.
9. Denoth Lippuner A, Julou T, Barral Y (2014) Budding yeast as a model organism to study the effects of age. FEMS Microbiol Rev 38: 300–325.
10. Arlia-Ciommo A, Leonov A, Piano A, et al. (2014) Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae. Microb Cell Graz Austria 1: 163–178.
11. Choi K-M, Lee C-K (2015) Cellular Longevity of Budding Yeast During Replicative and Chronological Aging, In: Mori N, Mook-Jung I (Eds.), Aging Mechanisms: Longevity, Metabolism, and Brain Aging, Tokyo, Springer Japan, 89–109.
12. Müller I, Zimmermann M, Becker D, et al. (1980) Calendar life span versus budding life span of Saccharomyces cerevisiae. Mech Ageing Dev 12: 47–52.
13. Steinkraus KA, Kaeberlein M, Kennedy BK (2008) Replicative aging in yeast: the means to the end. Annu Rev Cell Dev Biol 24: 29–54.
14. Steffen KK, Kennedy BK, Kaeberlein M (2009) Measuring Replicative Life Span in the Budding Yeast. JoVE J Vis Exp e1209.
15. Oliveira AV, Vilaça R, Santos CN, et al. (2017) Exploring the power of yeast to model aging and age-related neurodegenerative disorders. Biogerontology 18: 3–34.
16. Kaeberlein M, Burtner CR, Kennedy BK (2007) Recent developments in yeast aging. PLoS Genet 3: e84.
17. Hu J, Wei M, Mirisola MG, et al. (2013) Assessing Chronological Aging in Saccharomyces cerevisiae, In: Galluzzi L, Vitale I, Kepp O, et al. (Eds.), Cell Senescence: Methods and Protocols, Totowa, NJ, Humana Press, 463–472.
18. Millard PJ, Roth BL, Thi HP, et al. (1997) Development of the FUN-1 family of fluorescent probes for vacuole labeling and viability testing of yeasts. Appl Environ Microbiol 63: 2897–2905.
19. Teng X, Hardwick JM (2009) Reliable Method for Detection of Programmed Cell Death in Yeast, In: Erhardt P, Toth A (Eds.), Apoptosis: Methods and Protocols, Second Edition, Totowa, NJ, Humana Press, 335–342.
20. Murakami C, Kaeberlein M (2009) Quantifying Yeast Chronological Life Span by Outgrowth of Aged Cells. JoVE J Vis Exp e1156.
21. Murakami CJ, Burtner CR, Kennedy BK, et al. (2008) A method for high-throughput quantitative analysis of yeast chronological life span. J Gerontol A Biol Sci Med Sci 63: 113–121.
22. Longo VD, Antebi A, Bartke A, et al. (2015) Interventions to Slow Aging in Humans: Are We Ready? Aging Cell 14: 497–510.
23. Cuanalo-Contreras K, Moreno-Gonzalez I (2019) Natural Products as Modulators of the Proteostasis Machinery: Implications in Neurodegenerative Diseases. Int J Mol Sci 20: 4666.
24. Klaips CL, Jayaraj GG, Hartl FU (2018) Pathways of cellular proteostasis in aging and disease. J Cell Biol 217: 51–63.
25. Kaushik S, Cuervo AM (2015) Proteostasis and aging. Nat Med 21: 1406–1415.
26. Winklhofer KF, Tatzelt J, Haass C (2008) The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. EMBO J 27: 336–349.
27. Pan H, Finkel T (2017) Key proteins and pathways that regulate lifespan. J Biol Chem 292: 6452–6460.
28. Ottens F, Franz A, Hoppe T (2021) Build-UPS and break-downs: metabolism impacts on proteostasis and aging. Cell Death Differ 28: 505–521.
29. Cuanalo-Contreras K, Mukherjee A, Soto C (2013) Role of Protein Misfolding and Proteostasis Deficiency in Protein Misfolding Diseases and Aging. Int J Cell Biol 2013: e638083.
30. Giampieri F, Afrin S, Forbes-Hernandez TY, et al. (2019) Autophagy in Human Health and Disease: Novel Therapeutic Opportunities. Antioxid Redox Signal 30: 577–634.
31. Hetz C (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 13: 89–102.
32. Yamamoto K, Sato T, Matsui T, et al. (2007) Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1. Dev Cell 13: 365–376.
33. Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493: 338–345.
34. Kenyon CJ (2010) The genetics of ageing. Nature 464: 504–512.
35. Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 124: 471–484.
36. Dazert E, Hall MN (2011) mTOR signaling in disease. Curr Opin Cell Biol 23: 744–755.
37. Kaeberlein M, Powers RW, Steffen KK, et al. (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310: 1193–1196.
38. Jia K, Chen D, Riddle DL (2004) The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Dev Camb Engl 131: 3897–3906.
39. Harrison DE, Strong R, Sharp ZD, et al. (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460: 392–395.
40. Vellai T, Takacs-Vellai K, Zhang Y, et al. (2003) Influence of TOR kinase on lifespan in C. elegans. Nature 426: 620–620.
41. Kapahi P, Zid BM, Harper T, et al. (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol CB 14: 885–890.
42. Stanfel MN, Shamieh LS, Kaeberlein M, et al. (2009) The TOR pathway comes of age. Biochim Biophys Acta 1790: 1067–1074.
43. Powers RW, Kaeberlein M, Caldwell SD, et al. (2006) Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev 20: 174–184.
44. Bonawitz ND, Chatenay-Lapointe M, Pan Y, et al. (2007) Reduced TOR Signaling Extends Chronological Life Span via Increased Respiration and Upregulation of Mitochondrial Gene Expression. Cell Metab 5: 265–277.
45. Wei M, Fabrizio P, Hu J, et al. (2008) Life Span Extension by Calorie Restriction Depends on Rim15 and Transcription Factors Downstream of Ras/PKA, Tor, and Sch9. PLOS Genet 4: e13.
46. Medvedik O, Lamming DW, Kim KD, et al. (2007) MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae. PLoS Biol 5: e261.
47. Riesen M, Morgan A (2009) Calorie restriction reduces rDNA recombination independently of rDNA silencing. Aging Cell 8: 624–632.
48. Noda T, Ohsumi Y (1998) Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 273: 3963–3966.
49. Finkel T, Deng C-X, Mostoslavsky R (2009) Recent progress in the biology and physiology of sirtuins. Nature 460: 587–591.
50. Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13: 2570–2580.
51. Kennedy BK, Austriaco NR, Zhang J, et al. (1995) Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae. Cell 80: 485–496.
52. Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289: 2126–2128.
53. Solis GM, Petrascheck M (2011) Measuring Caenorhabditis elegans Life Span in 96 Well Microtiter Plates. J Vis Exp JoVE 2496.
54. Ruderman N, Prentki M (2004) AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat Rev Drug Discov 3: 340–351.
55. de Cabo R, Carmona-Gutierrez D, Bernier M, et al. (2014) The Search for Antiaging Interventions: From Elixirs to Fasting Regimens. Cell 157: 1515–1526.
56. Erjavec N, Cvijovic M, Klipp E, et al. (2008) Selective benefits of damage partitioning in unicellular systems and its effects on aging. Proc Natl Acad Sci 105: 18764–18769.
57. AMPK Legere Pharmaceuticals. Available from: https://www.legerepharm.com/ampk/.
58. Carman GM, Han G-S (2011) Regulation of Phospholipid Synthesis in the Yeast Saccharomyces cerevisiae. Annu Rev Biochem 80: 859–883.
59. Alberts B (2019) Essential Cell Biology, W.W. Norton & Company.
60. Simons K (2011) The Biology of Lipids: Trafficking, Regulation, and Function, Cold Spring Harbor Laboratory Press.
61. Haucke V, Di Paolo G (2007) Lipids and lipid modifications in the regulation of membrane traffic. Curr Opin Cell Biol 19: 426–435.
62. Carman GM, Henry SA (1999) Phospholipid biosynthesis in the yeast Saccharomyces cerevisiae and interrelationship with other metabolic processes. Prog Lipid Res 38: 361–399.
63. Ahmed S, Shah P, Ahmed O (2022) Biochemistry, Lipids, StatPearls, Treasure Island (FL), StatPearls Publishing.
64. Rajakumari S, Grillitsch K, Daum G (2008) Synthesis and turnover of non-polar lipids in yeast. Prog Lipid Res 47: 157–171.
65. Gaspar ML, Jesch SA, Viswanatha R, et al. (2008) A block in endoplasmic reticulum-to-Golgi trafficking inhibits phospholipid synthesis and induces neutral lipid accumulation. J Biol Chem 283: 25735–25751.
66. Dickson RC (2008) Thematic review series: sphingolipids. New insights into sphingolipid metabolism and function in budding yeast. J Lipid Res 49: 909–921.
67. Malanovic N, Streith I, Wolinski H, et al. (2008) S-adenosyl-L-homocysteine hydrolase, key enzyme of methylation metabolism, regulates phosphatidylcholine synthesis and triacylglycerol homeostasis in yeast: implications for homocysteine as a risk factor of atherosclerosis. J Biol Chem 283: 23989–23999.
68. Han G-S, Wu W-I, Carman GM (2006) The Saccharomyces cerevisiae Lipin homolog is a Mg2+-dependent phosphatidate phosphatase enzyme. J Biol Chem 281: 9210–9218.
69. Rattray JB, Schibeci A, Kidby DK (1975) Lipids of yeasts. Bacteriol Rev 39: 197–231.
70. Carman GM, Henry SA (1989) Phospholipid biosynthesis in yeast. Annu Rev Biochem 58: 635–669.
71. Oshiro J, Han GS, Carman GM (2003) Diacylglycerol pyrophosphate phosphatase in Saccharomyces cerevisiae. Biochim Biophys Acta 1635: 1–9.
72. Strahl T, Thorner J (2007) Synthesis and function of membrane phosphoinositides in budding yeast, Saccharomyces cerevisiae. Biochim Biophys Acta 1771: 353–404.
73. Martin CE, Oh C-S, Jiang Y (2007) Regulation of long chain unsaturated fatty acid synthesis in yeast. Biochim Biophys Acta 1771: 271–285.
74. Becker GW, Lester RL (1977) Changes in phospholipids of Saccharomyces cerevisiae associated with inositol-less death. J Biol Chem 252: 8684–8691.
75. Greenberg ML, Lopes JM (1996) Genetic regulation of phospholipid biosynthesis in Saccharomyces cerevisiae. Microbiol Rev 60: 1–20.
76. Chen M, Hancock LC, Lopes JM (2007) Transcriptional regulation of yeast phospholipid biosynthetic genes. Biochim Biophys Acta 1771: 310–321.
77. Klug L, Daum G (2014) Yeast lipid metabolism at a glance. FEMS Yeast Res 14: 369–388.
78. Takaku H, Matsuzawa T, Yaoi K, et al. (2020) Lipid metabolism of the oleaginous yeast Lipomyces starkeyi. Appl Microbiol Biotechnol 104: 6141–6148.
79. Mohammad K, Orfanos E, Titorenko VI (2021) Caloric restriction causes a distinct reorganization of the lipidome in quiescent and non-quiescent cells of budding yeast. Oncotarget 12: 2351–2374.
80. Masoro E (2002) Caloric Restriction: A Key to Understanding and Modulating Aging., Amsterdam, Elsevier Science.
81. Goldberg AA, Bourque SD, Kyryakov P, et al. (2009) Effect of calorie restriction on the metabolic history of chronologically aging yeast. Exp Gerontol 44: 555–571.
82. NIH (2018) National Institute on Aging, Calorie Restriction and Fasting Diets: What Do We Know?, 2018. Available from: http://www.nia.nih.gov/news/calorie-restriction-and-fasting-diets-what-do-we-know.
83. Longo VD, Mattson MP (2014) Fasting: Molecular Mechanisms and Clinical Applications. Cell Metab 19: 181–192.
84. Mattson MP (2014) Interventions that Improve Body and Brain Bioenergetics for Parkinson’s Disease Risk Reduction and Therapy. 1–13.
85. Moskalev A, Chernyagina E, Kudryavtseva A, et al. (2017) Geroprotectors: A Unified Concept and Screening Approaches. Aging Dis 8: 354–363.
86. Eisenberg T, Knauer H, Schauer A, et al. (2009) Induction of autophagy by spermidine promotes longevity. Nat Cell Biol 11: 1305–1314.
87. Hubbard BP, Sinclair DA (2014) Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol Sci 35: 146–154.
88. Sinclair DA, Guarente L Small-Molecule Allosteric Activators of Sirtuins - PMC. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018738/.
89. Madeo F, Carmona-Gutierrez D, Kepp O, et al. (2018) Spermidine delays aging in humans. Aging 10: 2209–2211.
90. Madeo F, Eisenberg T, Pietrocola F, et al. (2018) Spermidine in health and disease. Science 359: eaan2788.
91. Madeo F, Pietrocola F, Eisenberg T, et al. (2014) Caloric restriction mimetics: towards a molecular definition. Nat Rev Drug Discov 13: 727–740.
92. Leonov A, Arlia-Ciommo A, Piano A, et al. (2015) Longevity extension by phytochemicals. Mol Basel Switz 20: 6544–6572.
93. Moskalev A, Chernyagina E, de Magalhães JP, et al. (2015) Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease. Aging 7: 616–628.
94. Arlia-Ciommo A, Leonov A, Mohammad K, et al. (2018) Mechanisms through which lithocholic acid delays yeast chronological aging under caloric restriction conditions. Oncotarget 9: 34945–34971.
95. Dakik P, Rodriguez MEL, Junio JAB, et al. (2020) Discovery of fifteen new geroprotective plant extracts and identification of cellular processes they affect to prolong the chronological lifespan of budding yeast. Oncotarget 11: 2182–2203.
96. Lutchman V, Medkour Y, Samson E, et al. (2016) Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes. Oncotarget 7: 16542–16566.
97. Medkour Y, Mohammad K, Arlia-Ciommo A, et al. (2019) Mechanisms by which PE21, an extract from the white willow Salix alba, delays chronological aging in budding yeast. Oncotarget 10: 5780–5816.
98. Richard VR, Bourque SD, Titorenko VI (2014) Metabolomic and lipidomic analyses of chronologically aging yeast. Methods Mol Biol Clifton NJ 1205: 359–373.
99. Titorenko VI, Terlecky SR (2011) Peroxisome Metabolism and Cellular Aging. Traffic 12: 252–259.
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

Downloads per month over past year

Research related to the current document (at the CORE website)
- Research related to the current document (at the CORE website)
Back to top Back to top