Spermidine

Based on the provided literature, the scientific consensus indicates that the natural polyamine spermidine plays a vital role in cell growth, survival, and stress protection by inducing autophagy(definition) [1, 4, 5]. Across model organisms including yeast, flies, worms, and mice, spermidine supplementation or high-polyamine diets consistently extend lifespan and provide cardioprotective benefits [1, 2, 4, 8]. Mechanistically, spermidine acts as an acetylase inhibitor that stimulates autophagy independently of SIRT1—specifically by inhibiting the acetyltransferase EP300—and influences processes such as eIF5A hypusination and translation regulation [3, 5, 6, 7]. Because endogenous polyamine levels decline continuously with age in somatic tissues, supplementation has emerged as a promising strategy to combat age-related functional decline, including B cell senescence(definition) and overall somatic and neural senescence [4, 7, 8].

Despite robust preclinical evidence in model organisms, open questions remain regarding the translation of these findings into clinical practice [9]. While geroscience frameworks highlight polyamines as targets for healthy longevity and age-related conditions like sarcopenia, the maturity of clinical evidence and optimal therapeutic delivery strategies in humans require further validation [9, 10].

Overall, the strength of evidence is exceptionally strong and convergent regarding spermidine's mechanisms of action and lifespan extension in model organisms [1–8], but remains emergent regarding its efficacy and translational application in human clinical populations [9, 10].