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Volume 27
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10.3390/ijms27010464
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Calorie Restriction Suppresses Premature Ageing in Pro-Apoptotic Yeast Mutants Through an Autophagy-Independent Mechanism

by
Benedetta Caraba
1,
Mariarita Stirpe
1,
Vanessa Palermo
1,
Alessia Ayala Alban
1,
Arianna Montanari
1,
Michele Maria Bianchi
1,
Claudio Falcone
1 and
Cristina Mazzoni
1,2,*
1
Department of Biology and Biotechnologies “C. Darwin”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy
2
Water Research Institute, National Research Council (IRSA-CNR), 00010 Rome, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(1), 464; https://doi.org/10.3390/ijms27010464 (registering DOI)
Submission received: 3 November 2025 / Revised: 28 December 2025 / Accepted: 30 December 2025 / Published: 1 January 2026
(This article belongs to the Special Issue Stress Response Research: Yeast as Models: 2nd Edition)
Review Reports Versions Notes

Abstract

The budding yeast Saccharomyces cerevisiae has long served as a valuable model for investigating the molecular mechanisms underlying aging. Calorie restriction (CR) is a well-established intervention that extends lifespan across species, yet the underlying molecular mechanisms remain incompletely understood. In this study, we examined the effects of CR on the chronological lifespan, oxidative stress response, and autophagic activity of the Saccharomyces cerevisiae mutant Sclsm4Δ1, which exhibits premature aging and elevated reactive oxygen species (ROS) levels due to defects in mRNA decapping and processing-bodies (PB) dynamics. We found that both moderate (0.1% glucose) and extreme (water incubation) CR significantly extended the lifespan of Sclsm4Δ1 mutants and markedly reduced intracellular ROS accumulation without activating autophagy. These findings indicate that the beneficial effects of CR stem from improved redox homeostasis and metabolic adaptation, rather than from canonical autophagic pathways. Similar protective effects were observed in a chromosomal lsm4Δ1 mutant generated via CRISPR–Cas9, confirming that CR rescues aging-related phenotypes in different genetic backgrounds. These insights reinforce the roles of nutrient signaling, RNA metabolism, and redox balance in lifespan regulation, offering new perspectives on the conserved anti-aging effects of calorie restriction.
Keywords: autophagy; aging; calorie restriction; LSM4 autophagy; aging; calorie restriction; LSM4

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MDPI and ACS Style

Caraba, B.; Stirpe, M.; Palermo, V.; Ayala Alban, A.; Montanari, A.; Bianchi, M.M.; Falcone, C.; Mazzoni, C. Calorie Restriction Suppresses Premature Ageing in Pro-Apoptotic Yeast Mutants Through an Autophagy-Independent Mechanism. Int. J. Mol. Sci. 2026, 27, 464. https://doi.org/10.3390/ijms27010464

AMA Style

Caraba B, Stirpe M, Palermo V, Ayala Alban A, Montanari A, Bianchi MM, Falcone C, Mazzoni C. Calorie Restriction Suppresses Premature Ageing in Pro-Apoptotic Yeast Mutants Through an Autophagy-Independent Mechanism. International Journal of Molecular Sciences. 2026; 27(1):464. https://doi.org/10.3390/ijms27010464

Chicago/Turabian Style

Caraba, Benedetta, Mariarita Stirpe, Vanessa Palermo, Alessia Ayala Alban, Arianna Montanari, Michele Maria Bianchi, Claudio Falcone, and Cristina Mazzoni. 2026. "Calorie Restriction Suppresses Premature Ageing in Pro-Apoptotic Yeast Mutants Through an Autophagy-Independent Mechanism" International Journal of Molecular Sciences 27, no. 1: 464. https://doi.org/10.3390/ijms27010464

APA Style

Caraba, B., Stirpe, M., Palermo, V., Ayala Alban, A., Montanari, A., Bianchi, M. M., Falcone, C., & Mazzoni, C. (2026). Calorie Restriction Suppresses Premature Ageing in Pro-Apoptotic Yeast Mutants Through an Autophagy-Independent Mechanism. International Journal of Molecular Sciences, 27(1), 464. https://doi.org/10.3390/ijms27010464

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