Quantifiable biomarkers of normal aging in the Japanese medaka fish (Oryzias latipes).

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2010-10-11

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Abstract

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.

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10.1371/journal.pone.0013287

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Hinton, DE (2010). Quantifiable biomarkers of normal aging in the Japanese medaka fish (Oryzias latipes). PLoS One, 5(10). p. e13287. 10.1371/journal.pone.0013287 Retrieved from https://hdl.handle.net/10161/4576.

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Hinton

David E. Hinton

Nicholas Distinguished Professor Emeritus of Environmental Quality

The Hinton laboratory focuses on mechanistic toxicity in all life stages of small, aquarium model fish and in selected species with particular environmental relevance (freshwater and marine). With the latter, investigations focus on stressor responses and include follow up studies after oil spills. Studies with the laboratory model fish take advantage of the compressed life cycle to improve understanding of organellar, cellular and tissues responses that arise after exposure and follow either a temporal and/or a concentration gradient. At the end of these serial examinations, we have pioneered the use of high resolution light and fluorescent microscopy and electron microscopy in these small fish species to better understand resultant phenotypes and to correlate structural alteration with molecular biological studies. In this way we are anchoring phenotypes with gene expression. In individual fish where specific genes have been mutated (Collaboration with Dr. Keith Cheng, Hershey Medical Center, Hershey, PA) or in individuals exposed to organic substances of known or expected toxicity, structural analysis at various levels of biological organization enables integration across all levels of biological organization enabling whole body phenomics. Special projects include The Duke Superfund Research Center, 2P42-ESO10356-10A2, supported by NIH/NIEHS. Studies investigate responses of fish to polycyclic aromatic hydrocarbons and include early life stages and multigenerational effects. Contaminated and reference sites are included in these investigations of feral fish. Also, we receive funding as part of theme 2 of the Center for Environmental Implications of Nano Technology (CEINT). Our studies seek to determine whether there are specific toxic consequences upon exposure to nano silver (Ag NPs) versus exposure to conventional silver. We hosted Na Zheng (Angie), Visiting Investigator, Associate Professor, Northeast Institute of Geography and Agricultural Ecology, Chinese Academy of Sciences. She was the recipient of a K.C. Wong award supporting her role as visiting investigator. Together, we investigated metals mixtures and embryo toxicity. We collaborate with Stella Marinakos, Pratt School and CEINT on the synthesis and refinement of nanoselenium. This complements work done over the past year with seleno-methionine and sodium selenite in parental and embryo exposures. We continue to investigate ways to assess whole body responses of aquarium model fish and to link phenotype to genotype. Collaboration with the Stapleton laboratory has investigated alterations in embryo and larval zebrafish exposed to flame retardant compounds and selected metabolites. Here our morphologic investigations have helped to differentiate between delayed development and toxicity in the developing eye.


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