AimWe examined the changes in oxidative stress, mitochondrial function and muscle atrophy during aging in mice.MethodsWe used 6‐, 12‐ and 24‐month (6 M, 12 M and 24 M)‐old C57BL/6J mice. Skeletal muscles were removed from the lower limb and used for quantitative real‐time polymerase chain reaction, immunoblotting and histological analyses.ResultsThe muscle weight and myocyte cross‐sectional area were significantly decreased in the 12 M and 24 M mice compared with those of the 6 M mice. The levels of the oxidative stress markers, nicotinamide adenine dinucleotide phosphate oxidase 2, nicotinamide adenine dinucleotide phosphate oxidase 4, mitochondrial 4‐hydroxy‐2‐nonenal and 3‐nitrotyrosine, were significantly higher in the 24 M mice compared with those of the 6 M mice. Furthermore, the 24 M mice had lower levels of mitochondrial markers, peroxisome proliferator‐activated receptor gamma coactivator 1 (PGC)‐α, peroxisome proliferator‐activated receptor gamma coactivator‐1β, sirtuin‐1, adenosine triphosphate synthase mitochondria F1 complex α subunit 1 and mitochondrial cytochrome c oxidase 1. The ubiquitin–proteasome pathway genes muscle ring finger‐1 and atrogin‐1 were significantly upregulated in the 12 M and 24 M mice, and protein synthesis markers (phosphorylated‐Akt and ‐p70 ribosomal S6 kinase) were significantly lower in the 24 M mice compared with the 6 M mice (all P < 0.05).ConclusionsThese findings have important implications for the mechanisms that underlie sarcopenia and frailty processes. Geriatr Gerontol Int 2020; 20: 78–84.

Therefore, CR with intensive PA may have beneficial effects on coronary plaque regression in patients with ACS. Recently, advances in coronary plaque imaging, such as serial integrated backscatter intravascular ultrasound (IB-IVUS), have enabled physicians to observe the morphology of the plaque and accurately measure plaque volume (PV). Indeed, recent studies on statins using IB-IVUS have demonstrated significant plaque regression and stabilization. 7,8 Currently, however, there are no studies on the effect of CR involving intensive PA on PV and components using IB-IVUS. The aim of this study was therefore to investigate the effects of CR involving intensive PA on coronary PV and components in patients with ACS. C omprehensive cardiac rehabilitation (CR) is an established multidisciplinary secondary prevention program in patients with acute coronary syndrome (ACS), those receiving coronary artery bypass grafting (CABG), and those with heart failure. 1 CR is effective in modulating risk factors and reducing the incidence of future cardiovascular events. 2 According to the guidelines of the Japanese Circulation Society and the American Association of Cardiovascular and Pulmonary Rehabilitation, it is recommended to perform aerobic exercises, such as walking, running, and cycling, for ≥30 min each time, 3-4 times per week, based on exercise tolerance test. 3 Comprehensive CR and/or multifactorial intervention has been shown to inhibit angiographic minimal lumen stenosis. 4,5 We recently showed that coronary plaque changes in patients with ACS were significantly and negatively correlated with physical activity

Background: Muscle wasting is a debilitating phenotype associated with chronic heart failure (CHF). We have previously demonstrated that angiotensin II (AII) directly induces muscle wasting in mice through the activation of NADPH oxidase (Nox). In this study, we tested the hypothesis that deficiency of NADPH oxidase 4 (Nox4), a major source of oxidative stress, ameliorates AII-induced muscle wasting through the regulation of redox balance.Methods and Results: Nox4 knockout (KO) and wild-type (WT) mice were used. At baseline, there were no differences in physical characteristics between the WT and KO mice. Saline (vehicle, V) or AII was infused via osmotic minipumps for 4 weeks, after which, the WT + AII mice showed significant increases in Nox activity and NOX4 protein compared with the WT + V mice, as well as decreases in body weight, gastrocnemius muscle weight, and myocyte cross-sectional area. These changes were significantly attenuated in the KO + AII mice (27 ± 1 vs. 31 ± 1 g, 385 ± 3 vs. 438 ± 13 mg, and 1,330 ± 30 vs. 2281 ± 150 μm2, respectively, all P < 0.05). The expression levels of phospho-Akt decreased, whereas those of muscle RING Finger-1 (MuRF-1) and MAFbx/atrogin-1 significantly increased in the WT + AII mice compared with the WT + V mice. Furthermore, nuclear factor erythroid-derived 2-like 2 (Nrf2) and the expression levels of Nrf2-regulated genes significantly decreased in the WT + AII mice compared with the WT + V mice. These changes were significantly attenuated in the KO + AII mice (P < 0.05).Conclusion: Nox4 deficiency attenuated AII-induced muscle wasting, partially through the regulation of Nrf2. The Nox4–Nrf2 axis may play an important role in the development of AII-induced muscle wasting.

Background:The frailty state consists of not only physical but also psycho-emotional problems, such as cognitive dysfunction and depression as well as social problems. However, few reports have examined the relationship between frailty and anxiety levels in elderly patients undergoing cardiac rehabilitation (CR). Methods:We analyzed 255 patients (mean age: 74.9 ± 5.8 years, 67% male) who participated in early phase II CR at Juntendo University Hospital. At the beginning of CR, patients carried out selfassessments based on the Kihon Checklist (KCL) and the State Trait Anxiety Inventory Form (STAI). Patients were divided into three groups: frailty group (n = 99, 39%), pre-frailty group (n = 81, 32%), and non-frailty group (n = 75, 29%) according to the KCL. We assessed results from the KCL scores and its relationship with anxiety levels.Results: Among the three groups, there were no significant differences in age, underlying illnesses, or the prevalence of coronary risk factors. Depressive mood domains of the KCL were significantly higher in the frailty and pre-frailty groups than in the non-frailty groups (3.0 ± 1.5 vs. 1.4 ± 1.2 vs. 0.4 ± 0.6; P < 0.01). The state anxiety level was significantly higher in the frailty group than in the non-frailty group (41.6 ± 0.9 vs. 34.9 ± 1.0; P < 0.01). The trait anxiety levels were significantly higher in the frailty group and pre-frailty group than in the non-frailty group (45.5 ± 0.9 vs. 39.2 ± 1.0 vs. 35.1 ± 1.1; P < 0.01). State anxiety and trait anxiety also showed a significantly positive correlations with the KCL scores (r = 0.32 vs. 0.41, P < 0.01). Conclusions:Frailty scores were positively correlated not only with physical function but also with depression mood and anxiety levels in elderly patients undergoing early phase II CR. These results suggest that assessment of depressive mood and anxiety is also important in elderly patients undergoing early phase II CR.

Background: Delirium is a common occurrence in patients admitted to the intensive care unit and is related to mortality and morbidity. Malnutrition is a predisposing factor for the development of delirium. Nevertheless, whether the nutritional status on admission anticipates the development of delirium in patients with acute cardiovascular diseases remains unknown. Objective: This study aims to assess the correlation between the nutritional status on admission using the nutritional index and the development of delirium in the coronary intensive care unit. Design: We examined 653 consecutive patients (mean age: 70 ± 14 years) admitted to the coronary intensive care unit of Juntendo University Hospital between January 2015 and December 2016. We evaluated three nutritional indices frequently used to assess the nutritional status, i.e., Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT). We defined delirium as patients with a delirium score >4 using the Intensive Care Delirium Screening Checklist. Results: Delirium was present in 58 patients. All nutritional indices exhibited a tendency for malnutrition in the delirium group compared with the non-delirium group (GNRI, 86.5 ± 9.38 versus 91.6 ± 9.89; PNI, 36.4 ± 6.95 versus 41.6 ± 7.62; CONUT, 5.88 ± 3.00 versus 3.61 ± 2.56; for all, p < 0.001). Furthermore, the maximum delirium score increased progressively from the low- to the high-risk group, as evaluated by each nutritional index (GNRI, PNI, CONUT; for all, p < 0.001). A multivariate analysis revealed that the PNI and CONUT were independent risk factors for the occurrence of delirium. Conclusions: A marked correlation exists between the nutritional index on admission, especially PNI and CONUT, and the development of delirium in patients with acute cardiovascular diseases, suggesting that malnutrition assessment upon admission could help identify patients at high risk of developing delirium.