Idh2 deficiency accelerates renal dysfunction in aged mice.
The free radical or oxidative stress theory of aging postulates that senescence is due to an accumulation of cellular oxidative damage, caused largely by reactive oxygen species (ROS) that are produced as by-products of normal metabolic processes in mitochondria. The oxidative stress may arise as a result of either increased ROS production or decreased ability to detoxify ROS. The availability of the mitochondrial NADPH pool is critical for the maintenance of the mitochondrial antioxidant system. The major enzyme responsible for generating mitochondrial NADPH is mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2). Depletion of IDH2 in mice (idh2-/-) shortens life span and accelerates the degeneration of multiple age-sensitive traits, such as hair grayness, skin pathology, and eye pathology. Among the various internal organs tested in this study, IDH2 depletion-induced acceleration of senescence was uniquely observed in the kidney. Renal function and structure were greatly deteriorated in 24-month-old idh2-/- mice compared with wild-type. In addition, disruption of redox status, which promotes oxidative damage and apoptosis, was more pronounced in idh2-/- mice. These data support a significant role for increased oxidative stress as a result of compromised mitochondrial antioxidant defenses in modulating life span in mice, and thus support the oxidative stress theory of aging.
['Lee|Su Jeong|SJ|', 'Cha|Hanvit|H|', 'Lee|Seoyoon|S|', 'Kim|Hyunjin|H|', 'Ku|Hyeong Jun|HJ|', 'Kim|Sung Hwan|SH|', 'Park|Jung Hyun|JH|', 'Lee|Jin Hyup|JH|', 'Park|Kwon Moo|KM|', 'Park|Jeen-Woo|JW|']
D000375:Aging D000818:Animals D007521:Isocitrate Dehydrogenase D007674:Kidney Diseases D008017:Life Expectancy D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D018384:Oxidative Stress D017382:Reactive Oxygen Species D015996:Survival Rate
Aging Mitochondria Redox status Antioxidant enzyme Knockout mice