Spermine and spermidine reversed age-related cardiac deterioration in rats. Zhang Hao,Wang Junying,Li Lingxu,Chai Nannan,Chen Yuhan,Wu Feixiang,Zhang Weihua,Wang Lina,Shi Sa,Zhang Li,Bian Shuling,Xu Changqing,Tian Ye,Zhao Yajun Oncotarget Aging is the most important risk factor for cardiovascular disease (CVD). Slowing or reversing the physiological impact of heart aging may reduce morbidity and mortality associated with age-related CVD. The polyamines, spermine (SP) and spermidine (SPD) are essential for cell growth, differentiation and apoptosis, and levels of both decline with age. To explore the effects of these polyamines on heart aging, we administered SP or SPD intraperitoneally to 22- to 24-month-old rats for 6 weeks. Both treatments reversed and inhibited age-related myocardial morphology alterations, myocardial fibrosis, and cell apoptosis. Using combined proteomics and metabolomics analyses, we identified proteins and metabolites up- or downregulated by SP and SPD in aging rat hearts. SP upregulated 51 proteins and 28 metabolites while downregulating 80 proteins and 29 metabolites. SPD upregulated 44 proteins and 24 metabolites and downregulated 84 proteins and 176 metabolites. These molecules were mainly associated with immune responses, blood coagulation, lipid metabolism, and glutathione metabolism pathways. Our study provides novel molecular information on the cardioprotective effects of polyamines in the aging heart, and supports the notion that SP and SPD are potential clinical therapeutics targeting heart disease. 10.18632/oncotarget.18334

Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function. Wang Junying,Li Shaoqi,Wang Ju,Wu Feixiang,Chen Yuhan,Zhang Hao,Guo Yubo,Lin Yan,Li Lingxu,Yu Xue,Liu Ting,Zhao Yajun Aging Polyamines have been shown to delay cellular and organismal aging and to provide cardiovascular protection in humans. Because age-related cardiovascular dysfunction is often accompanied by impaired mitochondrial biogenesis and function, we explored the ability of spermidine (SPD), a major mammalian polyamine, to attenuate cardiac aging through activation of mitochondrial biogenesis. Cardiac polyamine levels were reduced in aged (24-month-old) rats. Six-week SPD supplementation restored cardiac polyamine content, preserved myocardial ultrastructure, and inhibited mitochondrial dysfunction. Immunoblotting showed that ornithine decarboxylase (ODC) and SPD/spermine N1-acetyltransferase (SSAT) were downregulated and upregulated, respectively, in the myocardium of older rats. These changes were paralleled by age-dependent downregulation of components of the sirtuin-1/peroxisome proliferator-activated receptor gamma coactivator alpha (SIRT1/PGC-1α) signaling pathway, an important regulator of mitochondrial biogenesis. SPD administration increased SIRT1, PGC-1α, nuclear respiratory factors 1 and 2 (NRF1, NRF2), and mitochondrial transcription factor A (TFAM) expression; decreased ROS production; and improved OXPHOS performance in senescent (HO-treated) cardiomyocytes. Inhibition of polyamine biosynthesis or SIRT1 activity abolished these effects. PGC-1α knockdown experiments confirmed that SPD activated mitochondrial biogenesis through SIRT1-mediated deacetylation of PGC-1α. These data provide new insight into the antiaging effects of SPD, and suggest potential applicability to protect against deterioration of cardiac function with aging. 10.18632/aging.102647