Abstract
BackgroundSmall 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 FindingsThe 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.SignificanceThe 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.
Highlights
A number of invertebrate and vertebrate model organisms have been used to explore the root causes of aging
Overall growth and survival The study design involved the comparison of individuals from three age groups: young adults, mature adults, and adults that had survived beyond the mean or median lifespan
We characterized biomarkers of normal aging in a population of medaka fish that was maintained under laboratory conditions
Summary
A number of invertebrate and vertebrate model organisms have been used to explore the root causes of aging. Many small laboratory fish such as the guppy, the zebrafish, and the medaka, and the annual killifish are characterized by a regular time-dependent aging similar to that of other vertebrates [2,3,4,5]. The rationale for use of these species in experimental gerontology includes their short lifespans, the relatively low cost of maintaining large numbers of individuals for lifetime studies, and in many cases, a well-developed genetics. 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. 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
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