期刊
FRONTIERS IN PHYSIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2018.00242
关键词
PGC-1 alpha; aging; myocardium; remodeling; transcriptional regulation; heart
类别
资金
- Swiss National Science Foundation
- European Research Council (ERC) [616830-MUSCLE_NET]
- Swiss Cancer Research grant [KFS-3733-08-2015]
- Swiss Society for Research on Muscle Diseases (SSEM)
- SystemsX.ch
- Novartis Stiftung fur Medizinisch-Biologische Forschung
- University of Basel
- Fellowship for Excellence of the Biozentrum Basel International PhD Program
Aging is associated with a decline in cardiac function due to a decreased myocardial reserve. This adverse cardiac remodeling comprises of a variety of changes, including a reduction in mitochondrial function and a decline in the expression of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha), a central regulator of mitochondrial biogenesis and metabolic adaptation in the myocardium. To study the etiological involvement of PGC-1 alpha in cardiac aging, we used mouse models mimicking the modest down-and upregulation of this coactivator in the old and the exercised heart, respectively. Youngmice with reduced cardiac expression of PGC-1 alpha recapitulated part of the age-related impairment in mitochondrial gene expression, but otherwise did not aggravate the aging process. Inversely however, moderate overexpression of PGC-1 alpha counteracts numerous key age-related remodeling changes, e.g., by improving blood pressure, age-associated apoptosis, and collagen accumulation, as well as in the expression of many, but not all cardiac genes involved in mitochondrial biogenesis, dynamics, metabolism, calcium handling and contractility. Thus, while the reduction of PGC-1 alpha in the heart is insufficient to cause an aging phenotype, moderate overexpression reduces pathological remodeling of older hearts and could thereby contribute to the beneficial effects of exercise on cardiac function in aging.
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