Spermidine, a natural polyamine, binds and stabilizes DNA and RNA, has antioxidative activities, modulates enzyme functions, and is required for the regulation of translation[1-2]. Spermidine, also a natural autophagy inducer, has a variety of health effects, such as antitumor, antiaging, anti-inflammation, cardiovascular protection, and neuromodulation[3]. Spermidine contains three positively charged amino groups, and this structural characteristic is crucial for its functions[3].
In vitro, treatment of human colon carcinoma HCT 116 cells with 100µM Spermidine for 2h induced the dephosphorylation of protein tyrosine kinase 2β (PYK2) and cyclin-dependent kinase inhibitor 1B (p27Kip1)[4]. Exogenous supplementation with 4mM Spermidine on day 1 of aging markedly extended the lifespan of both wild-type BY4741 and DBY746 yeast cells[5].
In vivo, in mice subjected to optic nerve injury (ONI), oral administration of 30mM Spermidine via drinking water prevented the significant loss of retinal ganglion cells (RGCs) and the thinning of the inner retinal layer (IRL) observed in vehicle-treated controls[6]. C57BL/6 WT mice given lifelong access to drinking water containing 0.3mM Spermidine exhibited a significant extension in median lifespan[7]. Continuous administration of 3mM Spermidine in the drinking water of aged mice markedly reduced aortic collagen I expression and restored NO-mediated endothelium-dependent dilation to levels observed in young controls[8].
References:
[1] Hofer SJ, Simon AK, Bergmann M, Eisenberg T, Kroemer G, Madeo F. Mechanisms of spermidine-induced autophagy and geroprotection. Nat Aging. 2022;2(12):1112-1129.
[2] Madeo F, Eisenberg T, Pietrocola F, Kroemer G. Spermidine in health and disease. Science. 2018;359(6374):eaan2788.
[3] Zou D, Zhao Z, Li L, et al. A comprehensive review of spermidine: Safety, health effects, absorption and metabolism, food materials evaluation, physical and chemical processing, and bioprocessing. Compr Rev Food Sci Food Saf. 2022;21(3):2820-2842.
[4] Morselli E, Mariño G, Bennetzen MV, et al. Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. J Cell Biol. 2011;192(4):615-629.
[5] Eisenberg T, Knauer H, Schauer A, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009;11(11):1305-1314.
[6] Noro T, Namekata K, Kimura A, et al. Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury. Cell Death Dis. 2015;6(4):e1720.
[7] Eisenberg T, Abdellatif M, Schroeder S, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016;22(12):1428-1438.
[8] LaRocca TJ, Gioscia-Ryan RA, Hearon CM Jr, Seals DR. The autophagy enhancer spermidine reverses arterial aging. Mech Ageing Dev. 2013;134(7-8):314-320.
Spermidine是一种天然多胺，可通过与DNA/RNA结合并稳定其结构、发挥抗氧化活性、调节酶功能以及参与翻译调控来维持细胞稳态[1-2]。作为一种天然自噬诱导剂，Spermidine具有抗肿瘤、抗衰老、抗炎、心血管保护及神经调节等多重健康效应[3]。Spermidine含三个带正电的氨基，这一结构特征对其功能至关重要[3]。
在体外，用100µM的Spermidine处理人结肠癌HCT 116细胞2小时，可诱导蛋白酪氨酸激酶2β（PYK2）和细胞周期蛋白依赖性激酶抑制剂1B（p27Kip1）去磷酸化[4]。在酵母衰老模型中，衰老第1天添加4mM外源性Spermidine，显著延长野生型BY4741和DBY746菌株的寿命[5]。
在体内，视神经损伤（ONI）小鼠经饮水给予30mM的Spermidine后，显著抑制了视网膜神经节细胞（RGCs）的丢失和内视网膜层（IRL）变薄[6]。C57BL/6野生型小鼠终生饮用含0.3mM的Spermidine的水，中位寿命显著延长[7]。持续给予老年小鼠3mM的Spermidine饮水，可显著降低主动脉Ⅰ型胶原表达，并将NO介导的内皮依赖性舒张恢复至年轻对照水平[8]。