Recent research from the Institute of Molecular Biology and Biotechnology (IMBB) at the Foundation for Research and Technology-Hellas (FORTH), in collaboration with Paris Cité University and the University of Graz, has provided new insights into how spermidine, a natural polyamine, regulates autophagy—a cellular process crucial for recycling internal components—thereby promoting the anti-aging benefits of intermittent fasting. The findings were published last week in Nature Cell Biology.
The study, led by Dr. Ioanna Daskalaki and Dr. Ilias Gkikas under the guidance of Dr. Nektarios Tavernarakis (a professor at the University of Crete and Chairman of the Board of Directors at FORTH), in collaboration with teams headed by Dr. Guido Kroemer of Paris Cité University and Dr. Frank Madeo from the University of Graz, revealed that intermittent fasting elevates spermidine levels. This increase in spermidine enhances cellular resilience and survival by triggering autophagy.
Autophagy is a crucial mechanism that involves the breakdown and recycling of damaged or unnecessary cellular components.
Deficiencies in autophagy are associated with aging and various age-related conditions such as diabetes, cardiovascular disease, cancer, and neurodegenerative disorders.
The study also highlighted the significant impact of dietary habits—including caloric intake, fat consumption, and fasting—on the progression of chronic diseases, which are anticipated to become more prevalent in the coming years.
Dietary interventions like caloric restriction and intermittent fasting have been shown to decelerate aging and extend lifespan.
A core component of these interventions is maintaining cellular homeostasis by inducing autophagy.
Direct supplementation with spermidine presents an alternative approach for promoting autophagy and extending lifespan. However, the exact role of spermidine in the regulation of autophagy and aging during intermittent fasting was previously unclear.
By utilizing a variety of experimental models—ranging from nematodes (Caenorhabditis elegans) and yeast (Saccharomyces cerevisiae) to fruit flies (Drosophila melanogaster), mice (Mus musculus), and human cell lines—the research teams demonstrated that intermittent fasting increases spermidine levels within cells, which in turn activates autophagy and extends the lifespan of these organisms.
On the other hand, inhibiting spermidine synthesis using specific inhibitors negated the autophagy-induced lifespan benefits associated with intermittent fasting.
The study underscores the essential role of spermidine in managing autophagy during intermittent fasting, thereby enhancing longevity across multiple species. The findings suggest that the regulation of autophagy via spermidine and intermittent fasting is a process conserved across evolution, highlighting its importance in maintaining cellular balance across different organisms.
This research offers valuable insights into how dietary practices can impact human aging and proposes new strategies for combating age-related diseases, with the goal of improving both lifespan and quality of life in older adults.
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