| First Author | Lee SJ | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 493 |
| Issue | 1 | Pages | 34-39 |
| PubMed ID | 28928092 | Mgi Jnum | J:250795 |
| Mgi Id | MGI:6103511 | Doi | 10.1016/j.bbrc.2017.09.082 |
| Citation | Lee SJ, et al. (2017) Idh2 deficiency accelerates renal dysfunction in aged mice. Biochem Biophys Res Commun 493(1):34-39 |
| abstractText | 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. |
