title: Mitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle.
abstract: Mitochondrial health is critical to physiological function, particularly in tissues with high ATP turnover, such as striated muscle. It has been postulated that derangements in skeletal muscle mitochondrial function contribute to impaired physical function in older adults. Here, we determined mitochondrial respiratory capacity and coupling control in skeletal muscle biopsies obtained from young and older adults. Twenty-four young (28 ± 7 yr) and thirty-one older (62 ± 8 yr) adults were studied. Mitochondrial respiration was determined in permeabilized myofibers from the vastus lateralis after the addition of substrates oligomycin and CCCP. Thereafter, mitochondrial coupling control was calculated. Maximal coupled respiration (respiration linked to ATP production) was lower in muscle from older vs. young subjects (P < 0.01), as was maximal uncoupled respiration (P = 0.06). Coupling control in response to the ATP synthase inhibitor oligomycin was lower in older adults (P < 0.05), as was the mitochondria flux control ratio, coupled respiration normalized to maximal uncoupled respiration (P < 0.05). Calculation of respiratory function revealed lower respiration linked to ATP production (P < 0.001) and greater reserve respiration (P < 0.01); i.e., respiratory capacity not used for phosphorylation in muscle from older adults. We conclude that skeletal muscle mitochondrial respiratory capacity and coupling control decline with age. Lower respiratory capacity and coupling efficiency result in a reduced capacity for ATP production in skeletal muscle of older adults.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, Texas; Shriners Hospitals for Children, Galveston, Texas; cr2porte@utmb.edu.
authors.forename: Craig
authors.initials: C
authors.lastname: Porter
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, Texas; Shriners Hospitals for Children, Galveston, Texas; Departments of Pediatrics and Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas; Arkansas Children's Hospital Research Institute, and Arkansas Children's Nutrition Center, Little Rock, Arkansas;
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Hurren
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, Texas; Departments of Pediatrics and Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas; Arkansas Children's Hospital Research Institute, and Arkansas Children's Nutrition Center, Little Rock, Arkansas;
authors.forename: Matthew V
authors.initials: MV
authors.lastname: Cotter
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, Texas; Shriners Hospitals for Children, Galveston, Texas;
authors.forename: Nisha
authors.initials: N
authors.lastname: Bhattarai
authors.affiliation: Department of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas; and.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Reidy
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Edgar L
authors.initials: EL
authors.lastname: Dillon
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.
authors.forename: William J
authors.initials: WJ
authors.lastname: Durham
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Demidmaa
authors.initials: D
authors.lastname: Tuvdendorj
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Melinda
authors.initials: M
authors.lastname: Sheffield-Moore
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Elena
authors.initials: E
authors.lastname: Volpi
authors.affiliation: Shriners Hospitals for Children, Galveston, Texas; Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Labros S
authors.initials: LS
authors.lastname: Sidossis
authors.affiliation: Department of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas; and.
authors.forename: Blake B
authors.initials: BB
authors.lastname: Rasmussen
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, Texas; Shriners Hospitals for Children, Galveston, Texas; Departments of Pediatrics and Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas; Arkansas Children's Hospital Research Institute, and Arkansas Children's Nutrition Center, Little Rock, Arkansas;
authors.forename: Elisabet
authors.initials: E
authors.lastname: Børsheim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D015331:Cohort Studies; D015536:Down-Regulation / Q000187:drug effects; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D042963:Electron Transport Complex II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D009210:Myofibrils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D061209:Proton Ionophores / Q000494:pharmacology; D052097:Quadriceps Muscle / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology; D055815:Young Adult
chemical_list: D009840:Oligomycins; D061209:Proton Ionophores; D014475:Uncoupling Agents; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I