We measured proteasome activities and the levels of proteasome subunits in dermal fibroblasts from individuals aged 20-82 years. Proteasome activities changed with age in a biphasic manner, decreasing significantly up to 50 years of age and showing no significant change between 50 and 78 years of age. Similarly, proteasome activities in replicatively senescent dermal fibroblasts showed a passage-dependent biphasic change. We confirmed that the decreases in proteasome activities were accompanied by the accumulation of oxidized and ubiquitinated proteins. The decline in proteasome activities in aging fibroblasts was associated with a decrease in the expression of proteasome subunits. We found that the restoration of the normal level of proteasome catalytic subunits, using a lentivirus gene-delivery system, decreased the severity of the aging markers in dermal fibroblasts from elderly donors. These findings suggest that proteasome malfunction may contribute to the aging process in human skin and that the maintenance of normal proteasome activities could delay skin aging.

Up-regulation of intercellular adhesion molecule-1 (ICAM-1) in the lung airway epithelium is associated with the epithelium-leukocyte interaction, critical for the pathogenesis of various lung airway inflammatory diseases such as asthma. However, little is known about how ICAM-1 is up-regulated in human airway epithelial cells. In this study, we show that tumor TNF-α induces monocyte adhesion to A549 human lung airway epithelium and also up-regulation of ICAM-1 expression. These effects were significantly diminished by pre-treatment with diphenyliodonium (DPI), an inhibitor of NADPH oxidase-like flavoenzyme. In addition, the level of reactive oxygen species (ROS) was increased in response to TNF-α in A549 cells, suggesting a potential role of ROS in the TNF-α-induced signaling to ICAM-1 expression and monocyte adhesion to airway epithelium. Further, we found out that expression of Rac

No abstract

Background and ObjectivesDespite amplified speech, listeners with hearing loss often report more difficulties understanding speech in background noise compared to normalhearing listeners. Various factors such as deteriorated hearing sensitivity, age, suprathreshold temporal resolution, and reduced capacity of working memory and attention can attribute to their sentence-in-noise problems. The present study aims to determine a primary explanatory factor for sentence-in-noise recognition difficulties in adults with or without hearing loss.Subjects and MethodsForty normal-hearing (NH) listeners (23-73 years) and thirty-four hearing-impaired (HI) listeners (24-80 years) participated for experimental testing. For both NH and HI group, the younger, middle-aged, older listeners were included. The sentence recognition score in noise was measured at 0 dB signal-to-noise ratio. The ability of temporal resolution was evaluated by gap detection performance using the Gaps-In-Noise test. Listeners’ short-term auditory working memory span was measured by forward and backward digit spans.ResultsOverall, the HI listeners’ sentence-in-noise recognition, temporal resolution abilities, and digit forward and backward spans were poorer compared to the NH listeners. Both NH and HI listeners had a substantial variability in performance. For NH listeners, only the digit backward span explained a small proportion of the variance in their sentence-in-noise performance. For the HI listeners, all the performance was influenced by age, and their sentence-in-noise difficulties were associated with various factors such as high-frequency hearing sensitivity, suprathreshold temporal resolution abilities, and working memory span. For the HI listeners, the critical predictors of the sentence-in-noise performance were composite measures of peripheral hearing sensitivity and suprathreshold temporal resolution abilities.ConclusionsThe primary explanatory factors for the sentence-in-noise recognition performance differ between NH and HI listeners. Factors affecting sentence-in-noise recognition performance differed between NH and HI listeners. The working memory was the primary predictor of the sentence-in-noise scores for the NH individuals. In contrast, a combination of factors seemed to contributed to speech-in-noise understanding for the HI listeners. Given this, we must be careful not to generalize findings from the NH listeners to the HI individuals.

No abstract