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- Soung Hun Park
- Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah
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- Oh Sung Kwon
- Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah
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- Song-Young Park
- School of Health and Kinesiology, University of Nebraska, Omaha, Nebraska
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- Joshua C. Weavil
- Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah
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- Robert H. I. Andtbacka
- Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah
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- John R. Hyngstrom
- Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah
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- Van Reese
- Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah
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- Russell S. Richardson
- Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah
説明
<jats:p> Little is known about vascular mitochondrial respiratory function and the impact of age. Therefore, skeletal muscle feed arteries were harvested from young (33 ± 7 yr, n = 10), middle-aged (54 ± 5 yr, n = 10), and old (70 ± 7 yr, n = 10) subjects, and mitochondrial respiration as well as citrate synthase (CS) activity were assessed. Complex I (CI) and complex I + II (CI+II) state 3 respiration were greater in young (CI: 10.4 ± 0.8 pmol·s<jats:sup>−1</jats:sup>·mg<jats:sup>−1</jats:sup> and CI+II: 12.4 ± 0.8 pmol·s<jats:sup>−1</jats:sup>·mg<jats:sup>−1</jats:sup>, P < 0.05) than middle-aged (CI: 7 ± 0.6 pmol·s<jats:sup>−1</jats:sup>·mg<jats:sup>−1</jats:sup> and CI+II: 8.3 ± 0.5 pmol·s<jats:sup>−1</jats:sup>·mg<jats:sup>−1</jats:sup>) and old (CI: 7.2 ± 0.4 pmol·s<jats:sup>−1</jats:sup>·mg<jats:sup>−1</jats:sup> and CI+II: 7.6 ± 0.5 pmol·s<jats:sup>−1</jats:sup>·mg<jats:sup>−1</jats:sup>) subjects and, as in the case of complex II (CII) state 3 respiration, were inversely correlated with age [ r = −0.56 (CI), r = −0.7 (CI+II), and r = 0.4 (CII), P < 0.05]. In contrast, state 4 respiration and mitochondria-specific superoxide levels were not different across groups. The respiratory control ratio was greater in young (2.2 ± 0.2, P < 0.05) than middle-aged and old (1.4 ± 0.1 and 1.1 ± 0.1, respectively) subjects and inversely correlated with age ( r = −0.71, P < 0.05). As CS activity was inversely correlated with age ( r = −0.54, P < 0.05), when normalized for mitochondrial content, the age-related differences and relationships with state 3 respiration were ablated. In contrast, mitochondrion-specific state 4 respiration was now lower in young (15 ± 1.4 pmol·s<jats:sup>−1</jats:sup>·mg<jats:sup>−1</jats:sup>·U CS<jats:sup>−1</jats:sup>, P < 0.05) than middle-aged and old (23.4 ± 3.6 and 27.9 ± 3.4 pmol·s<jats:sup>−1</jats:sup>·mg<jats:sup>−1</jats:sup>·U CS<jats:sup>−1</jats:sup>, respectively) subjects and correlated with age ( r = 0.46, P < 0.05). Similarly, superoxide/CS levels were lower in young (0.07 ± 0.01) than old (0.19 ± 0.41) subjects and correlated with age ( r = 0.44, P < 0.05). Therefore, with aging, vascular mitochondrial respiratory function declines, predominantly as a consequence of falling mitochondrial content. However, per mitochondrion, aging likely results in greater mitochondrion-derived oxidative stress, which may contribute to age-related vascular dysfunction. </jats:p><jats:p> NEW & NOTEWORTHY This study determined, for the first time, that vascular mitochondrial oxidative respiratory capacity, oxidative coupling efficiency, and mitochondrial content fell progressively with advancing age. In terms of single mitochondrion-specific respiration, the age-related differences were completely ablated and the likelihood of free radical production increased progressively with advancing age. This study reveals that vascular mitochondrial respiratory capacity declines with advancing age, as a consequence of falling mitochondrial content, as does oxidative coupling efficiency. </jats:p>
収録刊行物
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- American Journal of Physiology-Heart and Circulatory Physiology
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American Journal of Physiology-Heart and Circulatory Physiology 315 (6), H1660-H1669, 2018-12-01
American Physiological Society