Abstract
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.
Highlights
Age-related diseases are major contributors to high morbidity and mortality rates in aging populations
Age-related phenotype changes were observed in rat hearts, including myocardial morphology changes, myocardial fibrosis, and cell apoptosis
Age-induced cardiomyopathy in the mammalian heart is characterized by myocardial hypertrophy, fibrosis, and a predisposition towards cardiomyocyte apoptosis
Summary
Age-related diseases are major contributors to high morbidity and mortality rates in aging populations. Polyamines (PAs) are small, linear or occasionally branched polycations derived from amino acids, and are found in almost all eukaryotic cells. They are essential for cell proliferation, differentiation, and apoptosis [1, 2], and function as anti-inflammatories, anti-oxidants, and free radical scavengers [3,4,5]. Accumulating evidence indicates that polyamine levels are higher in the immature heart and decrease with age in male rats [12]. Our previous study suggested that exogenous polyamine protects against reperfusion injury by inhibiting mitochondrial permeability transition pore (mPTP) opening in isolated rat hearts [14]. To the best of our knowledge, no definitive information is available regarding the effect of exogenous polyamines on rat heart aging
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