HISTOCOMPATIBILITY SYSTEMS AND AGING

组织相容性系统和老化

• 批准号: 3090887
• 负责人: ROY L. WALFORD
• 金额: $ 16.55万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1990-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3090887
• 关键词: aging; immunogenetics; major histocompatibility complex

The project will investigate the hypothesis that the major histocompatibility complex is one of the key gene systems regulating biologic aging, and that it does so by integrating antibiosenescent properties of the immune system, a number of chemical pathways, particularly the p-450 mixed function oxidases, some DNA-repair mechanisms, and the neuroendocrine system. Existing evidence that all these systems are linked to or influenced by the MHC will be extended in studies of congenic mice and their F1 and F2 hybrids. A program will be developed to investigate the interrelation of MHC genetics and age-related alterations in a variety of functions. These so-called "biomarkers" of aging will include immunological, biochemical and complex physiological function tests applied in both cross-sectional and longitudinal studies, and will require development of micro-methods for the latter. The immunogenetics and other pertinent parameters of the deer mouse (which has a 7-year life span) will be investigated preparatory to comparative and interactive work with the common laboratory mouse (the first task being to establish Peromyscus as a "gerontologic" animal). The project is health related in that it seeks to locate what may be the single genetic basis for aging, and hence for the increasing vulnerability and disease susceptibility that comes with the passage of time in human and animal populations.

该项目将调查主要的假设 组织相容性复合物是调节的关键基因系统之一 生物衰老，并通过整合抗蛋白质来做到这一点 免疫系统的特性，许多化学途径， 特别是P-450混合功能氧化酶，某些DNA修复机制， 和神经内分泌系统。 现有的证据表明所有这些系统 与MHC相关或受到MHC的影响将扩大 先天小鼠及其F1和F2杂种。 将开发一个程序 研究MHC遗传学和与年龄相关的变化的相互关系 在各种功能中。 这些所谓的衰老的“生物标志物”将 包括免疫学，生化和复杂的生理功能测试 应用于横截面和纵向研究，将需要 后者的微方法的开发。 免疫遗传学和其他 鹿鼠的相关参数（具有7年寿命）将 可以调查与比较和互动工作的准备 普通实验室鼠标（第一个任务是将peromyscus建立为 “老年学”动物）。 该项目与健康有关，因为它试图找到可能是什么 衰老的单个遗传基础，因此增加了脆弱性 和疾病的敏感性随着人类和 动物种群。

项目成果

Age-related down regulation of hepatic cytochrome P1-450, P3-450, catalase and CuZn-superoxide dismutase RNA.

肝细胞色素 P1-450、P3-450、过氧化氢酶和 CuZn 超氧化物歧化酶 RNA 与年龄相关的下调。

• DOI: 10.1016/0047-6374(90)90038-h
• 发表时间: 1990
• 期刊: Mechanisms of ageing and development
• 影响因子: 5.3
• 作者: Mote,PL;Grizzle,JM;Walford,RL;Spindler,SR
• 通讯作者: Spindler,SR

DNA damage and repair in female C57BL/10 mice of different ages injected with the carcinogen benzo[a]pyrene-trans-7,8-diol.

注射致癌物质苯并[a]芘-反式-7,8-二醇的不同年龄雌性C57BL/10小鼠的DNA损伤和修复。

• DOI: 10.1016/0921-8734(89)90006-4
• 发表时间: 1989
• 期刊: Mutation research
• 作者: Ball,SS;Neshat,MS;Mickey,MR;Walford,RL
• 通讯作者: Walford,RL

Supernumerary ovarian grafts in aging C57BL/6J mice reveal complexities in the neuroendocrine impairments of acyclic mice.

衰老 C57BL/6J 小鼠的多余卵巢移植揭示了无周期小鼠神经内分泌损伤的复杂性。

• DOI: 10.1095/biolreprod36.4.961
• 发表时间: 1987
• 期刊: Biology of reproduction
• 影响因子: 3.6
• 作者: Flurkey,K;Anderson,CP;May,PC;Finch,CE
• 通讯作者: Finch,CE

Suppressive effect of O,O-dimethyl, S-ethyl phosphorothioate on immune response.

O,O-二甲基,S-乙基硫代磷酸酯对免疫反应的抑制作用。

• DOI: 10.1080/15287398609530945
• 发表时间: 1986
• 期刊: Journal of toxicology and environmental health
• 作者: Thomas,IK;Koizumi,A;Imamura,T
• 通讯作者: Imamura,T

Effects exerted by prostaglandins and indomethacin on the immune response during aging.

前列腺素和吲哚美辛对衰老过程中免疫反应的影响。

• DOI: 10.1159/000212759
• 发表时间: 1986
• 期刊: Gerontology
• 影响因子: 3.5
• 作者: Licastro,F;Walford,RL
• 通讯作者: Walford,RL