Azithromycin and Roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts

Here, we employed a “senolytic” assay system as a screening tool, with the goal of identifying and repurposing FDA-approved antibiotics, for the targeting of the senescent cell population. Briefly, we used two established human fibroblast cell lines (MRC-5 and/or BJ) as model systems to induce senescence, via chronic treatment with a DNA-damaging agent, namely BrdU (at a concentration of 100 μM for 8 days). Cell viability was then monitored by using the SRB assay, to measure protein content. As a consequence of this streamlined screening strategy, we identified Azithromycin and Roxithromycin as two novel clinically-approved senolytic drugs. However, Erythromycin – the very closely-related parent compound – did not show any senolytic activity, highlighting the dramatic specificity of these interactions. Interestingly, we also show that Azithromycin treatment of human fibroblasts was indeed sufficient to strongly induce both aerobic glycolysis and autophagy. However, the effects of Azithromycin on mitochondrial oxygen consumption rates (OCR) were bi-phasic, showing inhibitory activity at 50 μM and stimulatory activity at 100 μM. These autophagic/metabolic changes induced by Azithromycin could mechanistically explain its senolytic activity. We also independently validated our findings using the xCELLigence real-time assay system, which measures electrical impedance. Using this approach, we see that Azithromycin preferentially targets senescent cells, removing approximately 97% of them with great efficiency. This represents a near 25-fold reduction in senescent cells. Finally, we also discuss our current results in the context of previous clinical findings that specifically document the anti-inflammatory activity of Azithromycin in patients with cystic fibrosis – a genetic lung disorder that results in protein mis-folding mutations that cause protein aggregation

Real-time musculoskeletal visualization of muscle tension and joint reaction forces

International audienceThis paper presents a novel software that visualizes the physical burden of human body during movements. Its main objective is to support factory workers by monitoring the risk of physical health problems like low back pains. To achieve the goal, the software utilizes wearable sensors like IMUs to realize the measurement at a work-site. Several physical information like joint angles, joint torques, muscle tensions, joint reaction forces can be obtained by real-time musculoskeletal computation. The musculoskeletal information can be plotted and recorded by the visualization interface which is integrated to an ergonomic assessment software DhaibaWorks

Musculoskeletal Estimation Using Inertial Measurement Units and Single Video Image

International audienceWe address the problem of estimating the physical burden of a human body. This translates to monitor and estimate muscle tension and joint reaction forces of a mus-culoskeletal model in real-time. The system should minimize the discomfort generating by any sensors that needs to be fixed on the user. Our system combines a 3D pose estimation from vision and IMU sensors. We aim to minimize the number of IMU fixed to the subject while compensating the remaining lack of information with vision

Identification of Flying Humanoids and Humans

Abstract-The mass properties are important to control robot dynamics or study human dynamics. In our previous works, we proposed a method to identify inertial parameters of legged mechanisms from base-link dynamics, using generalized coordinates and external forces information. In this paper, we propose an identification method based on floating-base dynamics, when the system has no external force. Inertial parameters can be identified without force measurement, only from motion data. The method has been tested on two examples; a simple chain consisted of two links and the human body dynamics

AN EVALUATION OF PERFORMANCE OF A DOUBLE-LEG CIRCLE ON A POMMEL HORSE, AND A DESIRABLE PERFOMANCE PROPOSAL

For the evaluation of the performance of a double-leg circle on a pommel horse, we focused on the relation between the horizontal rotation of a body about the vertical axis in the center of a pommel horse and the hip rotation about the longitudinal axis of a body. Several gymnasts having different levels of skill were examined by using a motion capture system. The analysis shows that the horizontal rotation and the hip rotation are in good synchronization for the performance of a well-trained gymnast

Affects of "Age at Diagnosis" on Coronary Artery Lesions in Patients With Incomplete Kawasaki Disease

BACKGROUND AND OBJECTIVES : Diagnosis of Kawasaki disease (KD) is based on 5 clinical features. Incomplete KD (IKD), which has fewer features, is more common in infants and older children, in whom the rate of coronary artery aneurysms is paradoxically higher. We conducted this study to evaluate risk factors associated with age-at-diagnosis on coronary arterial lesions (CAL) in patients with IKD. SUBJECTS AND METHODS : Retrospective data from 396 patients with KD in a single center were collected from January 2003 to July 2007. Patients were grouped according to their age at diagnosis; Group A (/=5 years of age). RESULTS : Among a total of 396 patients with KD, 87 (22.0%) were in Group A, 246 (62.1%) in Group B, and 63 (15.9%) in Group C. In groups A and C, lag times for starting intravenous immunoglobulin (IVIG) were longer than in Group B. There were no differences in the incidence of IKD, late CAL, or rates of IVIG retreatment among the three groups. Among 174 patients with IKD, there were no age-related differences in late CAL incidence or IVIG retreatment. Compared with typical KD, duration of fever and lag times to start IVIG were longer, and the rate of IVIG retreatment was higher in IKD, but there was no difference in the risk of CAL between typical KD and IKD. CONCLUSION : In the management of KD, especially the incomplete type, age-associated factors appear not to be significant for predicting the development of CAL.ope