Research Articles:
Cell Stress, Vol. 9, No. 1, pp. 158 - 173; doi: 10.15698/cst2025.07.308
Sugar accelerates chronological aging in yeast via ceramides
1 Institute of Molecular Biosciences, University of Graz, NAWI Graz, Graz, Austria. 2 Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. 3 Center for society, knowledge and communication (7th faculty), University of Graz, Graz, Austria. 4 Field of Excellence BioHealth-University of Graz, Graz, Austria. 5 Chair of Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), University of Witten/Herdecke (UW/H), Witten, Germany. 6 BioTechMed Graz, Graz, Austria.
Keywords: aging, metabolic syndrom, cell stress, nutri-ent signaling, lipotoxicity, chronological lifespan, VAC8, TOR1, lipid homeostasis.
Received originally: 18/12/2024 Received in revised form: 14/05/2025
Accepted: 27/05/2025
Published: 11/07/2025
Correspondence:
Christoph Ruckenstuhl, ru.ruckenstuhl@uni-graz.at
Frank Madeo, frank.madeo@uni-graz.at
Conflict of interest statement: The authors declare no conflict of interest. FM has equity interest in Samsara Therapeutics and TLL, The Longevity Labs GmbH.
Please cite this article as: Vera Schmiedhofer, Julian Sommersguter-Wagner, Oskar Knittelfelder, Helmut Jungwirth, Gerald N. Rechberger, Didac Carmona-Gutierrez, Patrick Rockenfeller, Christoph Ruckenstuhl and Frank Madeo (2025). Sugar accelerates chronological aging in yeast via ceramides. Cell Stress 9: 158-173. doi: 10.15698/cst2025.07.308
Abstract
High carbohydrate intake, a characteristic of many Western diets, is a major contributor to age-associated pathologies. Here, we explored the molecular consequences of sugar overload during chronological aging in the yeast Saccharomyces cerevisiae. High levels of glucose and fructose resulted in a decrease of chronological lifespan as well as an increase of cell death, ROS and neutral lipids. Interestingly, these changes were accompanied by significantly altered ceramide profiles. Deletion of either the kinase Tor1, a master regulator of growth and autophagy in response to nutrients, or the vacuole-anchored receptor Vac8, an important player in various autophagy pathways, improved survival and normalized ceramide profiles. This suggests that ceramides might play a role in sugar stress-induced cell death. In line, pharmacological inhibition of sphingolipid synthesis normalized ceramide profiles and improved chronological lifespan, whereas pharmacologically induced ceramide accumulation decreased chronological lifespan. In sum, our findings causally link nutrient signaling and an altered ceramide profile to sugar cytotoxicity in aging yeast, providing a basis for further search of feasible interventions against sugar-induced cell death.
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Sugar accelerates chronological aging in yeast via ceramides by Schmiedhofer et al. is licensed under a Creative Commons Attribution 4.0 International License.
