Influence of aging on human sound localization

Errors in sound localization, associated with age-related changes in peripheral and central auditory function, can pose threats to self and others in a commonly encountered environment such as a busy traffic intersection. This study aimed to quantify the accuracy and precision (repeatability) of free-field human sound localization as a function of advancing age. Head-fixed young, middle-aged, and elderly listeners localized band-passed targets using visually guided manual laser pointing in a darkened room. Targets were presented in the frontal field by a robotically controlled loudspeaker assembly hidden behind a screen. Broadband targets (0.1–20 kHz) activated all auditory spatial channels, whereas low-pass and high-pass targets selectively isolated interaural time and intensity difference cues (ITDs and IIDs) for azimuth and high-frequency spectral cues for elevation. In addition, to assess the upper frequency limit of ITD utilization across age groups more thoroughly, narrowband targets were presented at 250-Hz intervals from 250 Hz up to ∼2 kHz. Young subjects generally showed horizontal overestimation (overshoot) and vertical underestimation (undershoot) of auditory target location, and this effect varied with frequency band. Accuracy and/or precision worsened in older individuals for broadband, high-pass, and low-pass targets, reflective of peripheral but also central auditory aging. In addition, compared with young adults, middle-aged, and elderly listeners showed pronounced horizontal localization deficiencies (imprecision) for narrowband targets within 1,250–1,575 Hz, congruent with age-related central decline in auditory temporal processing. Findings underscore the distinct neural processing of the auditory spatial cues in sound localization and their selective deterioration with advancing age

Human high-density lipoprotein particles prevent activation of the JNK pathway induced by human oxidised low-density lipoprotein particles in pancreatic beta cells.

AIMS/HYPOTHESIS: We explored the potential adverse effects of pro-atherogenic oxidised LDL-cholesterol particles on beta cell function. MATERIALS AND METHODS: Isolated human and rat islets and different insulin-secreting cell lines were incubated with human oxidised LDL with or without HDL particles. The insulin level was monitored by ELISA, real-time PCR and a rat insulin promoter construct linked to luciferase gene reporter. Cell apoptosis was determined by scoring cells displaying pycnotic nuclei. RESULTS: Prolonged incubation with human oxidised LDL particles led to a reduction in preproinsulin expression levels, whereas the insulin level was preserved in the presence of native LDL-cholesterol. The loss of insulin production occurred at the transcriptional levels and was associated with an increase in activator protein-1 transcriptional activity. The rise in activator protein-1 activity resulted from activation of c-Jun N-terminal kinases (JNK, now known as mitogen-activated protein kinase 8 [MAPK8]) due to a subsequent decrease in islet-brain 1 (IB1; now known as MAPK8 interacting protein 1) levels. Consistent with the pro-apoptotic role of the JNK pathway, oxidised LDL also induced a twofold increase in the rate of beta cell apoptosis. Treatment of the cells with JNK inhibitor peptides or HDL countered the effects mediated by oxidised LDL. CONCLUSIONS/INTERPRETATION: These data provide strong evidence that oxidised LDL particles exert deleterious effects in the progression of beta cell failure in diabetes and that these effects can be countered by HDL particles