Avian models for aging: telomeres and oxidative damage

鸟类衰老模型：端粒和氧化损伤

• 批准号: 6615929
• 负责人: CAROL M. VLECK
• 金额: $ 6.72万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-15 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6615929
• 关键词: Aves; DNA damage; DNA repair; age difference; aging; animal old age; biological models; blood tests; cell population study; chemical chain length; developmental genetics; enzyme activity; immature animal; longevity; mature animal; model design /development; oxidation; posttranslational modifications; songbirds; species difference; telomere

The research will determine the potential value of several bird species, which differ in life span, as models for the investigation of the biology of aging. Birds tend to be longer lived than mammals for any given body size, despite features of their biology (high metabolic rate, high body temperature) that should accelerate aging. Because they share a vertebrate genome with mammals, yet have a long independent history, study of their resistance to aging may reveal novel mechanisms that protect against aging, which can nevertheless be applied to prevention of aging damage in humans. Loss of ability for cell replication, caused by progressive shortening of terminal segments of chromosomal DNA called telomeres; and progressive oxidative damage to DNA and proteins are possible mechanisms of aging. This research will examine the mechanisms that permits exceptionally long-lived bird species to avoid telomere shortening as they age by measuring the expression and activity of telomerase, the enzyme complex that repairs telomeres. It will measure levels of oxidative damage in a variety of cell types in species that age at different rates and in individuals of different ages within each species, to determine whether long-lived species also have exceptional protection against oxidative damage. In mammal species including humans, telomerase is repressed in many somatic cell lines, perhaps as a mechanism for reducing the frequency of cancer. If long-lived birds continue to express telomerase in somatic cells throughout life, then how these species avoid telomerase's oncogenic effects will be of considerable interest. The results will indicate whether telomerase activity accounts for the protection of telomere length and life span in birds, provide models for searching for the mechanisms involved, and provide models for determining correlated traits that are necessary for long life.

该研究将确定几种鸟类的潜在价值，这些物种在寿命上有所不同，作为研究衰老生物学的模型。尽管其生物学特征（高代谢率，高体温）应加速衰老，但鸟类的生物量往往比哺乳动物长。由于它们与哺乳动物共享脊椎动物基因组，但具有悠久的独立历史，因此对它们对衰老的抵抗力的研究可能揭示了防止衰老的新型机制，但仍可以用于预防人类的衰老损害。细胞复制能力的丧失，是由称为端粒的染色体DNA的末端段逐渐缩短引起的；对DNA和蛋白质的进行性氧化损伤是衰老的可能机制。这项研究将检查允许异常长的鸟类物质的机制，以避免端粒缩短，它们通过测量端粒酶的表达和活性，端粒酶的表达和活性，端粒酶是维修端粒的酶复合物。它将测量各种细胞类型的氧化损伤水平，这些细胞类型以不同的速率和每个物种内不同年龄的个体年龄，以确定长寿命物种是否也具有针对氧化损害的特殊保护。在包括人类在内的哺乳动物物种中，端粒酶在许多体细胞系中受到抑制，也许是降低癌症频率的机制。如果长寿鸟类一生都继续在体细胞中表达端粒酶，那么这些物种如何避免端粒酶的致癌作用引起人们的关注。结果将表明端粒酶活动是否解释了鸟类长度和鸟类寿命的保护，为搜索所涉及的机制提供了模型，并提供了确定长寿所需的相关性状的模型。