Aging is associated with increased lipid peroxidation in human hearts, but not with mitochondrial respiratory chain enzyme defects.
BACKGROUND
Aging is associated with increased oxidative damage at multiple cellular and tissular levels. A decrease in mitochondrial function has repeatedly been advocated as a primary key event, especially on the basis of analysis of skeletal muscle mitochondria. However, some doubts on this issue have arisen when confounding variables (such as physical activity or smoking habit) have been taken into account in the analysis of mitochondrial respiratory chain (MRC) enzyme activities or when additional analytical parameters such as enzyme ratios have been considered.


OBJECTIVE
To determine whether oxidative damage and enzyme activities of the MRC are influenced by the aging process in human hearts.


METHODS
We studied cardiac muscle obtained from 59 organ donors (age: 56+/-12 years, 75% men). Oxidative membrane damage was evaluated through the assessment of lipid peroxidation. Absolute and relative enzyme activities (AEA and REA, respectively) of complex I, II, III and IV of the MRC were spectrophotometrically measured. Stoichiometric relationships among MRC complexes were also assessed through calculating MRC ratios. Linear regression analyses were employed to disclose any potential correlation between mitochondrial dysfunction and aging.


RESULTS
We found a progressive, significant increase of heart membrane lipid peroxidation with aging (P<0.05). Conversely, neither AEA nor REA decreased with age (P=n.s. for all complexes). Similarly to observations in other tissues, we found that stoichiometry of the MRC enzymes is maintained within a narrow range in human hearts. When the effects of aging on MRC ratios were explored, we failed again in demonstrating any subtle disarray.


CONCLUSIONS
MRC enzymes remain preserved in heart with aging, and thus they cannot be considered the main cause of the increased oxidative damage associated with aging.
Miró
O
O
Muscle Research Unit, Department of Internal Medicine, Hospital Clínic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Villarroel 170, 08036 University of Barcelona, Catalonia, Barcelona, Spain. omiro@medicina.ub.es
Casademont
J
J
Casals
E
E
Perea
M
M
Urbano-Márquez
A
A
Rustin
P
P
Cardellach
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D002462:Cell Membrane / Q000378:metabolism; D002648:Child; D004579:Electron Transport; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D000091402:Prohibitins; D013053:Spectrophotometry; D013482:Superoxide Dismutase / Q000032:analysis
D009097:Multienzyme Complexes; C000717331:PHB2 protein, human; D000091402:Prohibitins; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase