Aging is characterized by increased oxidative stress, chronic inflammation, and organ dysfunction, which occur in a progressive and irreversible manner. Superoxide dismutase (SOD) serves as a major antioxidant and neutralizes superoxide radicals throughout the body.In vivostudies have demonstrated that copper/zinc superoxide dismutase-deficient (Sod1^−/−) mice show various aging-like pathologies, accompanied by augmentation of oxidative damage in organs. We found that antioxidant treatment significantly attenuated the age-related tissue changes and oxidative damage-associated p53 upregulation inSod1^−/−mice. This review will focus on various age-related pathologies caused by the loss ofSod1and will discuss the molecular mechanisms underlying the pathogenesis inSod1^−/−mice.

In recent years, various quantitative and functional magnetic resonance imaging (MRI) sequences have been developed and used in clinical practice for the diagnosis of patients with low back pain (LBP). Until now, T2-weighted imaging (T2WI), a visual qualitative evaluation method, has been used to diagnose intervertebral disc (IVD) degeneration. However, this method has limitations in terms of reproducibility and inter-observer agreement. Moreover, T2WI observations do not directly relate with LBP. Therefore, new sequences such as T2 mapping, T1ρ mapping, and MR spectroscopy have been developed as alternative quantitative evaluation methods. These new quantitative MRIs can evaluate the anatomical and physiological changes of IVD degeneration in more detail than conventional T2WI. However, the values obtained from these quantitative MRIs still do not directly correlate with LBP, and there is a need for more widespread use of techniques that are more specific to clinical symptoms such as pain. In this paper, we review the state-of-the-art methodologies and future challenges of quantitative MRI as an imaging diagnostic tool for IVD degeneration and painful discs.

Redox imbalance elevates the reactive oxygen species (ROS) level in cells and promotes age-related diseases. Superoxide dismutases (SODs) are antioxidative enzymes that catalyze the degradation of ROS. There are three SOD isoforms: SOD1/CuZn-SOD, SOD2/Mn-SOD, and SOD3/EC-SOD. SOD2, which is localized in the mitochondria, is an essential enzyme required for mouse survival, and systemic knockout causes neonatal lethality in mice. To investigate the physiological function of SOD2 in adult mice, we generated a conditional Sod2 knockout mouse using a Cre-loxP system. When Sod2 was specifically deleted in the heart and muscle, all mice exhibited dilated cardiomyopathy (DCM) and died by six months of age. On the other hand, when Sod2 was specifically deleted in the skeletal muscle, mice showed severe exercise disturbance without morphological abnormalities. These provide useful model of DCM and muscle fatigue. In this review, we summarize the impact of antioxidants, which were able to regulate mitochondrial superoxide generation and improve the phenotypes of the DCM and the muscle fatigue in mice.

Oxidative stress is believed to greatly contribute to the pathogenesis of various diseases, including neurodegeneration. Impairment of mitochondrial energy production and increased mitochondrial oxidative damage are considered early pathological events that lead to neurodegeneration. Manganese superoxide dismutase (Mn-SOD, SOD2) is a mitochondrial antioxidant enzyme that converts toxic superoxide to hydrogen peroxide. To investigate the pathological role of mitochondrial oxidative stress in the central nervous system, we generated brain-specific SOD2-deficient mice (B-Sod2^−/−) usingnestin-Cre-loxpsystem. B-Sod2^−/−showed perinatal death, along with severe growth retardation. Interestingly, these mice exhibited spongiform neurodegeneration in motor cortex, hippocampus, and brainstem, accompanied by gliosis. In addition, the mutant mice had markedly decreased mitochondrial complex II activity, but not complex I or IV, in the brain based on enzyme histochemistry. Furthermore, brain lipid peroxidation was significantly increased in the B-Sod2^−/−, without any compensatory alterations of the activities of other antioxidative enzymes, such as catalase or glutathione peroxidase. These results suggest that SOD2 protects the neural system from oxidative stress in the perinatal stage and is essential for infant survival and central neural function in mice.

Rotator cuff degeneration is 1 of several factors that lead to rotator cuff tears; however, the mechanism of this degeneration remains unclear. We previously reported that deficiency of an antioxidant enzyme, superoxide dismutase 1 (Sod1), in mice induced degeneration in supraspinatus tendon entheses, a model that replicates human rotator cuff degeneration. In this study, we analyzed possible effects of vitamin C (VC), a major antioxidant, on the degenerative changes of supraspinatus entheses in Sod1 -/- mice. We administered VC or vehicle, distilled water, for 8 weeks to Sod1 -/- and wild-type male mice beginning at 12 weeks of age (n = 5-8 per group). When mice were 20 weeks of age, we sectioned rotator cuff tissue samples and performed hematoxylin-eosin and toluidine blue staining for quantitative histologic evaluation. VC administration, compared with vehicle administration, attenuated the histologic changes, including a misaligned 4-layered structure, fragmented tidemark, and toluidine blue staining, in the supraspinatus entheses of Sod1 -/- mice. In the quantitative histologic evaluation, all parameters were significantly decreased in Sod1 -/- mice compared with wild-type mice, except for the number of nonchondrocytes. We demonstrated that an antioxidant treatment, VC administration, attenuated the rotator cuff degeneration, similar to that observed in humans, that is caused by oxidative stress in Sod1 -/- mice. VC effects included improvements in quantitative histologic parameters and other histologic changes. These results suggest that VC treatment can prevent oxidative stress-induced degeneration of the rotator cuff.

Recent studies have shown that superoxide dismutase 1 (SOD1), SOD2, and SOD3 are significantly decreased in human osteoarthritic cartilage. SOD activity is a marker that can be used to comprehensively evaluate the enzymatic capacities of SOD1, SOD2, and SOD3; however, the trend of SOD activity in end-stage osteoarthritic tissues remains unknown. In the present study, we found that SOD activity in end-stage osteoarthritic synovium of the knee was significantly lower than that in control synovium without the influence of age. The SOD activity was significantly lower in the end-stage knee osteoarthritic cartilage than in the control, but a weak negative correlation was observed between aging and SOD activity. However, SOD activity in end-stage hip osteoarthritic cartilage was significantly lower than that in control cartilage without the influence of aging. The relationship between osteoarthritis and SOD activity was stronger than the relationship between aging and SOD activity. These results indicate that direct regulation of SOD activity in joint tissues may lead to suppression of osteoarthritis progression.