Author ORCID Identifier

Park - https://orcid.org/0000-0001-8576-7531

Document Type

Article

Publication Date

11-26-2018

Publication Title

American Journal of Physiology Heart and Circulatory Physiology

Volume

315

Issue

6

First Page

H1660

Last Page

H1669

Abstract

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−1·mg−1 and CI+II: 12.4 ± 0.8 pmol·s−1·mg−1, P < 0.05) than middle-aged (CI: 7 ± 0.6 pmol·s−1·mg−1 and CI+II: 8.3 ± 0.5 pmol·s−1·mg−1) and old (CI: 7.2 ± 0.4 pmol·s−1·mg−1 and CI+II: 7.6 ± 0.5 pmol·s−1·mg−1) 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−1·mg−1·U CS−1, P < 0.05) than middle-aged and old (23.4 ± 3.6 and 27.9 ± 3.4 pmol·s−1·mg−1·U CS−1, 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.

Comments

This is the accepted manuscript of an article published in the American Journal of Physiology Heart and Circulatory Physiology on November 26, 2018, the https://doi.org/10.1152/ajpheart.00324.2018

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