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Exp Gerontol. 2014 Oct;58:78-82. doi: 10.1016/j.exger.2014.07.008. Epub 2014 Jul 14.

Mitochondrial quality control and age-associated arterial stiffening.

Author information

1
Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: thomas.larocca@colorado.edu.
2
Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
3
Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: seals@colorado.edu.

Abstract

Stiffening of large elastic arteries with age increases the risk of cardiovascular diseases (CVD), but the underlying mechanisms are incompletely understood. We investigated the role of mitochondrial quality control (QC, i.e., mitophagy and biogenesis) in arterial stiffening with aging. In C57BL6 mice, aging was associated with impaired aortic expression of mitochondrial QC mediators, greater activation of the mitochondrial redox/stress sensor p66shc, elevated superoxide production and increased arterial stiffness-as indicated by ~25% higher aortic pulse wave velocity (aPWV). In old mice, supplementation with trehalose, a nutraceutical reported to enhance mitophagy, normalized mitochondrial QC markers, p66shc activation and superoxide production, and reduced aPWV and aortic collagen I (a structural protein that confers stiffness). In vitro experiments suggested that mitochondrial QC processes were enhanced in the aortas from old trehalose-treated mice, and in aortic rings studied ex vivo, both aging and treatment with the mitochondrial stressor rotenone were associated with increases in p66shc activation and intrinsic mechanical stiffness, whereas co-incubation with trehalose prevented these effects. Taken together, these findings suggest that mitochondrial stress/dysfunction as a result of impaired mitochondrial QC contributes to large elastic artery stiffening with age. Enhancing mitochondrial QC with agents such as trehalose may be a novel strategy for reducing age-associated arterial stiffness and CVD.

KEYWORDS:

Collagen; Mitochondrial biogenesis; Mitophagy

PMID:
25034910
PMCID:
PMC4252265
DOI:
10.1016/j.exger.2014.07.008
[Indexed for MEDLINE]
Free PMC Article

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