Aging of gonads, germ cells, and stem cells

性腺、生殖细胞和干细胞的老化

• 批准号: 7732292
• 负责人: Minoru Ko
• 金额: $ 30.33万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7732292
• 关键词: Address; Age; Age-Months; Aging; C57BL/6 Mouse; Caloric Restriction; Cell Aging; Cells; Chromatin Structure; Classification; Competence; DNA Methylation; DNA Microarray Chip; DNA Microarray format; Gene Expression; Gene Expression Profiling; Genes; Genome Stability; Genomics; Germ Cells; Germ Lines; Global Change; Goals; Gonadal structure; Human; Infertility; Longevity; Maternal Age; Mediating; Metaphase; Mitochondria; Modification; Molecular Profiling; Mus; Numbers; Oocytes; Organ; Ovary; Ovulation; Ovulation Inhibition; Oxidative Stress; Pattern; RNA Helicase; Reporting; Research Project Grants; Statistically Significant; Stem cells; Testis; Tissues; Transcript; Week; Work; age related; cell age; feeding; interest; neuronal cell body; reproductive; social; trend

In previous work, we compared the expression profiles of metaphase II oocytes collected from 5- to 6-week-old mice with those collected from 42- to 45-week-old mice. Among approximately 11,000 genes whose transcripts were detected in oocytes, about 5% (530) showed statistically significant expression changes, excluding a global decline in transcript abundance. Consistent with the generally accepted view of aging, the differentially expressed genes included many involved in mitochondrial function and oxidative stress. However, the expression of other genes involved in chromatin structure, DNA methylation, genome stability and RNA helicases was also altered, suggesting the existence of additional mechanisms for aging. During the last year, we examined global changes in gene expression patterns by DNA microarrays in ovaries and testes of C57BL/6 mice at 1, 6, 16, and 24 months of age. In addition, we compared a group of mice on ad libitum (AL) feeding with a group on lifespan-extending 40% calorie restriction (CR). We found that gene expression changes occurred in aging gonads, but were generally different from those in somatic organs during aging. The bulk of the changes in gonads were mostly related to gonad-specific functions. Ovaries showed extensive gene expression changes with age, especially in the period when ovulation ceases (from 6 to 16 months), whereas testes showed only limited age-related changes. The same trend was seen for the effects of CR: CR-mediated reversal of age-associated gene expression changes, reported previously in somatic organs, was limited to a small number of genes in gonads. Instead, in both ovary and testis, CR caused small and mostly gonad-specific effects: suppression of ovulation in ovary and activation of testis-specific genes in testis. Overall, the results are consistent with unique modes of aging and its modification by CR in testis and ovary.

在之前的研究中，我们比较了从5- 6周龄小鼠和42- 45周龄小鼠收集的中期II卵母细胞的表达谱。在卵母细胞中检测到约11,000个转录本的基因中，除转录本丰度的全球下降外，约5%（530个）的表达变化具有统计学意义。与普遍接受的衰老观点一致，差异表达的基因包括许多涉及线粒体功能和氧化应激的基因。然而，参与染色质结构、DNA甲基化、基因组稳定性和RNA解旋酶的其他基因的表达也发生了改变，这表明存在其他的衰老机制。