Research Paper Volume 12, Issue 1 pp 650—671
Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function
- 1 Department of Pathophysiology, Harbin Medical University, Harbin, China
- 2 Department of Medical Technology, Beijing Health Vocational College, Beijing, China
- 3 Affiliated Hospital of Hebei University, Baoding, China
- 4 Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
- 5 The Second Affiliated Hospital of Harbin Medical University, Harbin, China
- 6 Department of Pathophysiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China
- 7 Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University, Ministry of Education, Harbin, China
received: August 11, 2019 ; accepted: December 23, 2019 ; published: January 6, 2020 ;https://doi.org/10.18632/aging.102647
How to Cite
Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 (H2O2-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.