Aging increases mitochondrial DNA damage and oxidative stress in liver of rhesus monkeys.
While the mechanisms of cellular aging remain controversial, a leading hypothesis is that mitochondrial oxidative stress and mitochondrial dysfunction play a critical role in this process. Here, we provide data in aging rhesus macaques supporting the hypothesis that increased oxidative stress is a major characteristic of aging and may be responsible for the age-associated increase in mitochondrial dysfunction. We measured mitochondrial DNA (mtDNA) damage by quantitative PCR in liver and peripheral blood mononuclear cells of young, middle age, and old monkeys and show that older monkeys have increases in the number of mtDNA lesions. There was a direct correlation between the amount of mtDNA lesions and age, supporting the role of mtDNA damage in the process of aging. Liver from older monkeys showed significant increases in lipid peroxidation, protein carbonylations and reduced antioxidant enzyme activity. Similarly, peripheral blood mononuclear cells from the middle age group showed increased levels in carbonylated proteins, indicative of high levels of oxidative stress. Together, these results suggest that the aging process is associated with defective mitochondria, where increased production of reactive oxygen species results in extensive damage at the mtDNA and protein levels. This study provides valuable data based on the rhesus macaque model further validating age-related mitochondrial functional decline with increasing age and suggesting that mtDNA damage might be a good biomarker of aging.
Department of Pharmacology and Toxicology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
María del R
Mdel R
Castro
Edu
E
Suarez
Edmundo
E
Kraiselburd
Angel
A
Isidro
José
J
Paz
León
L
Ferder
Sylvette
S
Ayala-Torres
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D008930:Mitochondria, Liver / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D050050:Protein Carbonylation / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; D017382:Reactive Oxygen Species; D002374:Catalase; D005979:Glutathione Peroxidase