Arterial aging, characterized by stiffening of large elastic arteries and the development of arterial endothelial dysfunction, increases cardiovascular disease (CVD) risk. We tested the hypothesis that spermidine, a nutrient associated with the anti-aging process autophagy, would improve arterial aging. Aortic pulse wave velocity (aPWV), a measure of arterial stiffness, was ~20% greater in old (O, 28 months) compared with young C57BL6 mice (Y, 4 months, P < 0.05). Arterial endothelium-dependent dilation (EDD), a measure of endothelial function, was ~25% lower in O (P < 0.05 vs. Y) due to reduced nitric oxide (NO) bioavailability. These impairments were associated with greater arterial oxidative stress (nitrotyrosine), superoxide production, and protein cross-linking (advanced glycation end-products, AGEs) in O (all P < 0.05). Spermidine supplementation normalized aPWV, restored NO-mediated EDD and reduced nitrotyrosine, superoxide, AGEs and collagen in O. These effects of spermidine were associated with enhanced arterial expression of autophagy markers, and in vitro experiments demonstrated that vascular protection by spermidine was autophagy-dependent. Our results indicate that spermidine exerts a potent anti-aging influence on arteries by increasing NO bioavailability, reducing oxidative stress, modifying structural factors and enhancing autophagy. Spermidine may be a promising nutraceutical treatment for arterial aging and prevention of age-associated CVD.
Spermidine helps protect the cardiovascular system and reduces the risk of high blood pressure and cardiovascular disease. Another study analyzed dietary data from 24,000 United States adults and found that dietary intake of more spermidine was associated with a significant reduction in cardiovascular mortality.
The HFD accentuated weight gain as well as adiposity, while spermidine dramatically offset these changes. Interestingly, spermidine significantly improved glucose tolerance and insulin sensitiivity in young mice under HFD . Therefor, spermidine dramatically attenuates HFD-induced obesity.The autophagy inducer spermidine protects against metabolic dysfunction During overnutrition.
Memory performance was moderately enhanced in the spermidine group compared with placebo at the end of intervention (contrast mean = 0.17, 95% confidence interval [CI]: -0.01, 0.35, Cohen’s d = 0.77, 95% CI: 0, 1.53). Mnemonic discrimination ability improved in the spermidine-treated group with a medium effect size (mean difference = -0.11, 95% CI: -0.19, -0.03, Cohen’s d = 0.79, 95% CI: 0.01, 1.55). A similar effect was not found in the placebo-treated group (mean difference = 0.07, 95% CI: -0.13, 0.27, Cohen’s d = -0.20, 95% CI: -0.94, 0.54).Nutritional spermidine was associated with a positive impact on memory performance in older adults with subject cognitive decline. This beneficial effect might be mediated by stimulation of neuromodulatory actions in the memory system.
Inflammation significantly affects LFA-1 expression (Figure S1 in Supplementary Material) and hs-CRP is a marker of inflammation, with an acute increase in hs-CRP, indicating acute inflammation. In this analysis, the mean value of the relative blood SPM levels at 12 months compared to pre-intervention increased significantly by 1.08 ± 0.18 times (p = 0.019) in the intervention group, while those in the control group did not change (0.98 ± 0.20 times). The mean mono-CD11aMFI in the intervention group tended to decrease with time, and the change at 12 months was significantly lower than that in the control group (−247.83 ± 148.76 vs. −85.04 ± 257.39, p = 0.019)
