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

• Published in: PloS one Vol. 5; no. 10; p. e13287
• Main Authors: Ding, Lingling, Kuhne, Wendy W, Hinton, David E, Song, Jian, Dynan, William S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.10.2010; Public Library of Science (PLoS)
• Subjects: Adults; Age; Aging; Aging - physiology; Analysis; Animal tissues; Animals; Apoptosis; BASIC BIOLOGICAL SCIENCES; Biochemistry; Biological markers; Biomarkers; Biomarkers - metabolism; Biomedical research; Blood vessels; Brain; Degeneration; Dermis; Embryology; Environmental effects; Environmental stress; Epithelium; Eye - cytology; Eye - metabolism; Fibrosis; Fish; Fishes; Galactosidase; Gastroenterology and Hepatology/Hepatology; Gene expression; Genetics; Genomes; Geriatrics; In Situ Nick-End Labeling; Ionizing radiation; Laboratories; Life span; Liver; Liver - cytology; Liver - metabolism; Low cost; Medicine; Metabolism; Mortality; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Musculoskeletal system; Mutagenesis; Myocardium - cytology; Myocardium - metabolism; Neurodegeneration; Nothobranchius furzeri; Oryzias - physiology; Oryzias latipes; Oxidative stress; Pathogenesis; Pathology/Histopathology; Phagolysosomes; Retina; Science & Technology - Other Topics; Senescence; Skeletal muscle; Skin - cytology; Skin - metabolism; Steatosis; Studies; Survival analysis; Tissue analysis; Toxicology; Vacuoles; Vertebrates; Young adults; Zebrafish; β-Galactosidase; United States > US; Georgia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013287

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. 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. 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.