By HealthWires.net Staff
In a pioneering study that could reshape our understanding of how diet influences aging, researchers have uncovered the crucial role of polyamines, especially spermidine (SPD), in extending lifespan through intermittent fasting (IF) and nutrient deprivation. Conducted across multiple species, including yeast, fruit flies, worms, and mice, the study reveals intricate molecular mechanisms that drive the health benefits associated with fasting.
The Vital Role of Polyamines in Longevity
Polyamines are small organic compounds found in all living cells and are known to be involved in various cellular processes, including cell growth, gene expression, and the stabilization of DNA. This new research emphasizes their indispensable role in the longevity benefits of fasting.
- Yeast Experiments Highlight Polyamine Dependency: The study’s initial phase focused on yeast, a simple model organism often used in aging research. When yeast cells were subjected to a low-glucose environment—a condition mimicking nutrient deprivation—their lifespan extended significantly. However, when the gene SPE1, responsible for polyamine synthesis, was knocked out, this longevity benefit was lost. This suggests that polyamines, produced by SPE1, are crucial for the lifespan extension seen under nutrient-deprived conditions. Interestingly, when glucose levels were maintained at a standard concentration, the absence of SPE1 did not affect yeast lifespan, underscoring the specific role of polyamines in response to nutrient stress.
- Impact of Intermittent Fasting on Fruit Flies and Worms: Expanding the research to more complex organisms, the team examined the effects of intermittent fasting on fruit flies and worms. In fruit flies, especially females, an IF12:12 regimen—where the flies fast for 12 hours and feed for the next 12—significantly improved survival rates. However, when the flies were treated with DFMO, a chemical inhibitor of polyamine synthesis, these benefits were markedly reduced. Similar results were seen in worms, where the genetic inhibition of the odc-1 gene, a critical player in polyamine synthesis, led to diminished lifespan extension and reduced heat stress resistance. These findings strongly suggest that polyamine synthesis is a vital mechanism through which intermittent fasting exerts its health benefits.
Mice Models Unveil Cardioprotective and Anti-Inflammatory Effects
The study also delved into the effects of polyamines in mammals, using mice as models to explore more complex physiological processes like heart health and inflammation—both of which are significantly impacted by aging.
- Cardioprotection and Muscle Strength: In aged male mice, researchers applied an IF16:8 regimen, where mice fast for 16 hours and eat for 8 hours. Normally, this fasting protocol is known to protect heart health and improve muscle strength in aging mice. However, when DFMO was administered, effectively blocking the synthesis of polyamines, these benefits were completely negated. The DFMO-treated mice showed no improvements in heart function, muscle strength, or overall frailty, highlighting the indispensable role of polyamine synthesis in mediating the positive effects of intermittent fasting.
- Suppression of Inflammation: In a related experiment, a 24-hour fasting cycle (IF24:24) was shown to reduce systemic inflammation, a common issue in aging. However, when polyamine synthesis was inhibited by DFMO, this anti-inflammatory effect was lost. This suggests that polyamines are key players in the fasting-induced suppression of inflammation, a critical factor in aging and age-related diseases.
eIF5A Hypusination: The Universal Mechanism Behind Fasting’s Benefits
A particularly groundbreaking aspect of the study is the identification of eIF5A hypusination—a biochemical modification of the eIF5A protein—as a critical mechanism that links polyamines to the health benefits of fasting. eIF5A is a translation factor involved in protein synthesis, and its hypusination is driven by spermidine. The researchers discovered that fasting triggers this modification across all species studied, from yeast to humans, and that it is essential for the activation of autophagy—a cellular cleanup process that removes damaged components and is closely associated with longevity.
This hypusination process is vital not just for autophagy but also for the overall pro-longevity effects of fasting. Inhibition of eIF5A hypusination led to a significant reduction in these benefits, confirming its central role in fasting responses.
Potential Applications and Cautions in Human Health
The findings from this study open up exciting possibilities for enhancing human health through dietary interventions and targeted therapies. For example, spermidine supplementation could potentially amplify the benefits of fasting protocols, offering a non-invasive way to promote longevity and reduce the risk of age-related diseases.
However, the researchers also caution against a blanket approach to increasing polyamine levels. Polyamines are involved in cell growth, and elevated levels have been associated with the proliferation of cancer cells. Therefore, the implications of boosting polyamine synthesis, especially in individuals at risk of cancer, must be carefully evaluated. Future research will need to explore the delicate balance between promoting longevity and managing the risks associated with increased polyamine levels.
Conclusion: A New Frontier in Aging Research
This study marks a significant advance in our understanding of the molecular mechanisms behind fasting and its effects on aging. By highlighting the central role of polyamines, particularly through the process of eIF5A hypusination, researchers have paved the way for new therapeutic strategies that could one day be used to extend human healthspan and lifespan.
As the scientific community continues to explore the complex interactions between diet, fasting, and cellular health, studies like this one provide a foundation for developing novel interventions that could transform how we age.
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Source:
Hofer, S.J., Daskalaki, I., Bergmann, M. et al. Spermidine is essential for fasting-mediated autophagy and longevity. Nat Cell Biol (2024). https://doi.org/10.1038/s41556-024-01468-x
