Quantifiable Biomarkers of Normal Aging in the Japanese Medaka Fish (Oryzias latipes)
Quantifiable Biomarkers of Normal Aging in the Japanese Medaka Fish (Oryzias latipes)
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DOI：
10.1371/journal.pone.0013287
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发表时间：
2010-10-11
期刊：
影响因子：
3.7
通讯作者：
Dynan, William S.
中科院分区：
文献类型：
--
作者：
Ding, Lingling;Kuhne, Wendy W.;Dynan, William S.
背景资料：小型实验室鱼类与其他脊椎动物有许多解剖学和组织学特征，但可以以低成本大量饲养，用于终身研究。在这里，我们的生物标志物与日本青鳉（青鳉），已被广泛用于毒理学研究的物种，并具有潜在的效用作为一个模式生物实验老化research.Principal结果：青鳉的中位寿命约为22个月的实验室条件下，正常老化的特征。我们对来自年龄分组个体的组织进行了定量组织学分析，这些年龄分组个体代表年轻成人（6个月大）、成熟成人（16个月大）和存活超过中位寿命（24个月）的成人。24个月大个体的肝脏表现出广泛的形态变化，包括海绵状肝脏、脂肪变性、气球样变性、炎症和核固缩。肝实质细胞内有吞噬溶酶体、空泡和残留小体，肝窦血管充血。老年人的肝脏的特点是脂褐素沉积和TUNEL阳性凋亡细胞的数量增加。在16个月大的个体的肝脏中，在较小程度上观察到这些变性特征中的一些，但在6个月大的个体中没有观察到。真皮基底层的分裂细胞数量呈年龄依赖性下降，衰老相关β-半乳糖苷酶增加。老年人的心脏以纤维化和脂褐素沉积为特征。视网膜上皮也有色素细胞丢失。相比之下，年龄相关的变化并不明显，骨骼肌，眼透镜，或brain.Significance：结果提供了一组标记，可用于跟踪过程中的正常组织老化青鳉和评估环境压力的影响。
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 beta-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.