Quantifiable Biomarkers of Normal Aging in the Japanese Medaka Fish (Oryzias latipes)

BACKGROUND: Small laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies. Here we characterize biomarkers associated with normal aging in the Japanese medaka (Oryzias latipes), a species that has been widely used in toxicology studies and has potential utility as a model organism for experimental aging research. PRINCIPAL FINDINGS: The median lifespan of medaka was approximately 22 months under laboratory conditions. We performed quantitative histological analysis of tissues from age-grouped individuals representing young adults (6 months old), mature adults (16 months old), and adults that had survived beyond the median lifespan (24 months). Livers of 24-month old individuals showed extensive morphologic changes, including spongiosis hepatis, steatosis, ballooning degeneration, inflammation, and nuclear pyknosis. There were also phagolysosomes, vacuoles, and residual bodies in parenchymal cells and congestion of sinusoidal vessels. Livers of aged individuals were characterized by increases in lipofuscin deposits and in the number of TUNEL-positive apoptotic cells. Some of these degenerative characteristics were seen, to a lesser extent, in the livers of 16-month old individuals, but not in 6-month old individuals. The basal layer of the dermis showed an age-dependent decline in the number of dividing cells and an increase in senescence-associated β-galactosidase. The hearts of aged individuals were characterized by fibrosis and lipofuscin deposition. There was also a loss of pigmented cells from the retinal epithelium. By contrast, age-associated changes were not apparent in skeletal muscle, the ocular lens, or the brain. SIGNIFICANCE: The results provide a set of markers that can be used to trace the process of normal tissue aging in medaka and to evaluate the effect of environmental stressors

Combined Space and Alertness Related Therapy of Visual Hemineglect: Effect of Therapy Frequency

The combined efficacy of space- and alertness related training in chronic hemineglect was tested behaviorally and in a longitudinal fMRI study. Earlier results had shown that both space as well as alertness related training as single intervention methods lead to short term improvement which, however, is not stable for longer time periods. The neurobiological data obtained in these studies revealed differential cortical reorganization patterns for the two training approaches thereby leading to the hypothesis that a combination of both trainings might result in stronger and longer lasting effects. The results of our current study, however, – at least at first glance – do not clearly corroborate this hypothesis, because neither alertness training alone nor the combination with OKS on the group level led to significant behavioral improvement, although four of the six patients after alertness and even more after combined training showed a higher percentage of behavioral improvement than during baseline. Despite the lack of clearcut behavioral training induced improvement we found right parietal or fronto-parietal increase of activation in the imaging data immediately after combined training and at follow-up 3 weeks later. The study design had called for splitting up training time between the two training approaches in order to match total training time with our earlier single training studies. The results of our current study are discussed as a possible consequence of reduced training time and intensity of both training measures under the combined training situation