期刊
NATURE MEDICINE
卷 22, 期 12, 页码 1428-+出版社
NATURE PORTFOLIO
DOI: 10.1038/nm.4222
关键词
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资金
- Austrian Science Fund FWF (Austria) [P23490-B12, P24381, P 27893, I1000]
- BMWFW
- Karl-Franzens University
- Austrian Science Fund FWF [P27637-B28, P27183-B24]
- Austrian Heart Foundation (Osterreichischer Herzfonds)
- Austrian Academy of Sciences
- FWF [P27637-B28]
- Swedish Research Council [2015-05468]
- DFG [CRC1140]
- Swiss National Science Foundation [31003A-166482/1]
- Austrian Science Fund (FWF) [J3742-B28]
- NAWI Graz
- EU (FP7) program MEDIA
- German Research Foundation [SFB1002, TPA8]
- LeDucq Foundation
- Canceropole Ile-de-France
- Institut National du Cancer (INCa)
- European Research Council (ERC)
- LabEx Immuno-Oncology
- Paris Alliance of Cancer Research Institutes (PACRI)
- Helmholtz Portfolio Theme 'Metabolic Dysfunction and Common Disease (ICEMED)'
- Helmholtz Alliance ('Imaging and Curing Environmental Metabolic Diseases (ICEMED)')
- German Federal Ministry of Education and Research [01KX1012]
- Bundesministerium fur Bildung und Forschung [01GQ1420A]
- Forschungszentrum fur neurodegenerative Erkrankungen
- Deutsche Forschungsgemeinschaft [Exc 257]
- Austrian Research Promotion Agency FFG: ' Research Center of Excellence in Vascular Ageing-Tyrol, VASCage' - BMVIT [843536]
- Wirtschaftsagentur Wien
- Standortagentur Tirol
- National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas's NHS Foundation Trust
- King's College London
- King's College Hospital
- Austrian Science Fund (FWF) [P27637, P27183, P27893, J3742, P29262] Funding Source: Austrian Science Fund (FWF)
- Swedish Research Council [2015-05468] Funding Source: Swedish Research Council
- British Heart Foundation [FS/13/2/29892, FS/11/29/28759] Funding Source: researchfish
Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease.
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