Endogenous spermidine is crucial for rapamycin’s benefits, enhancing autophagy and extending lifespan. Blocking spermidine synthesis hinders these effects, highlighting its role in cellular health. Combining rapamycin with spermidine may optimise longevity interventions while mitigating side effects.
September 2024 – Autophagy
Key takeaways
- Spermidine is essential for autophagy and longevity: Spermidine, a naturally occurring polyamine, plays a crucial role in activating autophagy, the body’s cellular recycling process that removes damaged components and maintains cellular health. Its presence is vital for longevity benefits triggered by both fasting and rapamycin treatment. Without sufficient spermidine, these effects are significantly reduced, highlighting its importance in ageing interventions
- Fasting increases spermidine production, supporting healthy ageing: Nutrient deprivation, such as during fasting, triggers a natural surge in spermidine levels across multiple species, including humans. This increase initiates a chain reaction that enhances autophagy and promotes cellular renewal, ultimately contributing to improved healthspan and a slower ageing process
- Rapamycin’s anti-ageing effects rely on spermidine synthesis: Rapamycin, known for its ability to extend lifespan by inhibiting mTOR (a key growth regulator), depends on an increase in spermidine to activate autophagy. Blocking spermidine synthesis diminishes rapamycin’s ability to promote longevity, highlighting the interconnected nature of these pathways in supporting healthy ageing
While rapamycin effectively promotes longevity, it may have immunosuppressive side effects. Supplementing with spermidine or using rapamycin intermittently could counterbalance these drawbacks, offering a more refined approach to anti-ageing interventions while enhancing therapeutic outcomes.
Read the article at: Hofer, Sebastian J., et al. “A Surge in Endogenous Spermidine Is Essential for Rapamycin-Induced Autophagy and Longevity.” Autophagy, vol. 20, no. 12, 2024, pp. 2824–2826, https://doi.org/10.1080/15548627.2024.2396793.