Scientists discover why intermittent fasting has anti-aging effects

Recent research from the Institute of Molecular Biology and Biotechnology (IMBB) of the Foundation for Research and Technology-Hellas (FORTH), Paris Cité University, and the University of Graz has revealed how spermidine, a natural polyamine, plays a vital role in the anti-aging effects of intermittent fasting.

Published in Nature Cell Biology, the study highlights the mechanism by which spermidine regulates autophagy, a process essential for recycling cellular components, ultimately promoting healthier aging.

The research, led by Dr. Ioanna Daskalaki and Dr. Ilias Gkikas from IMBB, and directed by Dr. Nektarios Tavernarakis (Chairman of the Board of Directors at FORTH and Professor at the Medical School of the University of Crete), worked in collaboration with Dr. Guido Kroemer’s team from Paris Cité University and Dr. Frank Madeo’s group at the University of Graz.

Their findings demonstrate that intermittent fasting boosts levels of spermidine, which enhances the survival and resilience of cells by triggering autophagy.

Autophagy, the process of cellular recycling, helps eliminate non-functional components and damaged organelles. Defects in autophagy have been linked to aging and the development of age-related disorders such as diabetes, cardiovascular diseases, cancer, and neurodegenerative conditions.

The increase in chronic diseases due to poor dietary habits—such as high-fat diets, overnutrition, or even poor fasting practices—underscores the importance of understanding how autophagy can be controlled to mitigate aging.

The researchers show that caloric restriction and intermittent fasting, which both stimulate autophagy, are effective ways to delay aging and improve longevity. A key factor in this relationship is maintaining cellular homeostasis—keeping cells functioning properly by clearing out damaged components.

The direct administration of spermidine has been explored as another way to induce autophagy and slow down the aging process. However, the precise role of spermidine during intermittent fasting had remained unclear until now.

The team used a variety of experimental models, including nematodes (Caenorhabditis elegans), yeast (Saccharomyces cerevisiae), fruit flies (Drosophila melanogaster), mice (Mus musculus), and human cell lines, to investigate the effects of intermittent fasting on spermidine levels. They found that intermittent fasting raised the levels of spermidine, which, in turn, stimulated autophagy.

This process resulted in longer lifespans in the organisms studied. However, when spermidine synthesis was inhibited, the benefits of autophagy on lifespan were reduced, showing just how critical spermidine is to this cellular process.

The study reveals the universal, evolutionarily conserved role of spermidine in managing autophagy across different species, from yeast to humans. This conservation suggests spermidine’s central role in maintaining cellular homeostasis. By supporting autophagy, spermidine enables cells to function more efficiently, which contributes to longer life expectancy across a wide variety of organisms.

For humans, these findings offer new insights into how dietary habits can affect aging. Caloric restriction and intermittent fasting, when properly managed, could provide new strategies for combating age-related diseases. Enhancing autophagy through these interventions, or even through the direct administration of spermidine, may not only increase life expectancy but also improve the quality of life, particularly for the elderly.

According to Dr. Tavernarakis and his team, this research paves the way for innovative therapies targeting age-related diseases. “Our work demonstrates that spermidine is a powerful mediator of autophagy under intermittent fasting, and understanding this could lead to new approaches to improving longevity and health in old age,” he said.

The research also suggests that combining intermittent fasting with other autophagy-inducing strategies, such as spermidine supplementation, could offer a promising avenue for addressing the growing burden of chronic diseases associated with aging. As the global population continues to age, the need for such strategies becomes more pressing. In fact, the prevalence of chronic diseases is projected to increase significantly in the coming decades.

By shedding light on the biological processes underlying aging and disease, this research opens up possibilities for future studies exploring the potential of dietary interventions in human health. It also highlights the importance of autophagy as a central process in regulating longevity, offering hope for new, non-invasive treatments to combat aging and improve life quality as we grow older.

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