TY - JOUR
T1 - Effects of age and caloric restriction on mitochondrial protein oxidative damage in mice
AU - Li, Xiao Dong
AU - Rebrin, Igor
AU - Forster, Michael J.
AU - Sohal, Rajindar S.
N1 - Funding Information:
This study was supported by the grant R01 AG 13563 from the National Institutes of Health-National Institute on Aging . We are grateful to Dr. William C. Orr for his comments.
PY - 2012/1
Y1 - 2012/1
N2 - The hypothesis that life-span extension by caloric restriction (CR) is contingent upon the attenuation of macromolecular oxidative damage was tested in two different strains of mice: the C57BL/6, whose life span is extended by CR, and the DBA/2, in which CR has relatively minor or no impact on longevity. Mice were fed ad libitum (AL) or restricted to 40% lesser food, starting at 4 months of age. Protein damage was measured as protein-linked adducts of 4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA) in skeletal muscle mitochondria at 6 and 23 months of age. Protein-HNE and -MDA content increased with age in C57BL/6 mice and CR significantly attenuated these augmentations. Metalloprotease 1, NADP-dependent mitochondrial malic enzyme (isoform 2) and citrate synthase were identified by mass spectroscopy to contain HNE/MDA adducts. DBA/2 mice exhibited little effect of age or CR on protein HNE/MDA content in skeletal muscle mitochondria. In contrast, protein-HNE levels in liver mitochondria showed a significant increase with age in AL-fed mice of both strains, and CR caused significant attenuation of this damage. Overall, results indicated that the age-related increase in protein oxidative damage and its abatement by CR are genotype- and tissue-specific, and not a universal phenomenon.
AB - The hypothesis that life-span extension by caloric restriction (CR) is contingent upon the attenuation of macromolecular oxidative damage was tested in two different strains of mice: the C57BL/6, whose life span is extended by CR, and the DBA/2, in which CR has relatively minor or no impact on longevity. Mice were fed ad libitum (AL) or restricted to 40% lesser food, starting at 4 months of age. Protein damage was measured as protein-linked adducts of 4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA) in skeletal muscle mitochondria at 6 and 23 months of age. Protein-HNE and -MDA content increased with age in C57BL/6 mice and CR significantly attenuated these augmentations. Metalloprotease 1, NADP-dependent mitochondrial malic enzyme (isoform 2) and citrate synthase were identified by mass spectroscopy to contain HNE/MDA adducts. DBA/2 mice exhibited little effect of age or CR on protein HNE/MDA content in skeletal muscle mitochondria. In contrast, protein-HNE levels in liver mitochondria showed a significant increase with age in AL-fed mice of both strains, and CR caused significant attenuation of this damage. Overall, results indicated that the age-related increase in protein oxidative damage and its abatement by CR are genotype- and tissue-specific, and not a universal phenomenon.
KW - Food restriction
KW - HNE-protein conjugates
KW - Mitochondrial proteins
KW - Oxidative stress
KW - Protein oxidative damage
UR - http://www.scopus.com/inward/record.url?scp=84856221107&partnerID=8YFLogxK
U2 - 10.1016/j.mad.2011.12.001
DO - 10.1016/j.mad.2011.12.001
M3 - Article
C2 - 22182424
AN - SCOPUS:84856221107
SN - 0047-6374
VL - 133
SP - 30
EP - 36
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
IS - 1
ER -