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Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function.

ABSTRACT: 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-1?) signaling pathway, an important regulator of mitochondrial biogenesis. SPD administration increased SIRT1, PGC-1?, 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-1? knockdown experiments confirmed that SPD activated mitochondrial biogenesis through SIRT1-mediated deacetylation of PGC-1?. These data provide new insight into the antiaging effects of SPD, and suggest potential applicability to protect against deterioration of cardiac function with aging.

SUBMITTER: Wang J

PROVIDER: S-EPMC6977682 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function.

Wang Junying J Li Shaoqi S Wang Ju J Wu Feixiang F Chen Yuhan Y Zhang Hao H Guo Yubo Y Lin Yan Y Li Lingxu L Yu Xue X Liu Ting T Zhao Yajun Y

Aging 20200106 1

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 p ...[more]

PMID: 31907336

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Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function.

Publications

Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function.

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