Role of Telomere In Human Lymphocyte Function and Aging

端粒在人类淋巴细胞功能和衰老中的作用

• 批准号: 8335920
• 负责人: Nan ping Peter Weng
• 金额: $ 12.94万
• 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/8335920
• 关键词: Adult; Age; Aging; Apoptosis; B-Lymphocytes; Baltimore; Blood; Blood Cells; CD28 gene; Cell Aging; Cells; Cross-Sectional Studies; Elderly; Enzymes; Factor Analysis; Goals; Health; Human; Immune response; In Vitro; Length; Life; Longevity; Longitudinal Studies; Lymphocyte; Lymphocyte Activation; Lymphocyte Function; Malignant Neoplasms; Measures; Molecular; Obesity; Participant; Peripheral Blood Lymphocyte; Peripheral Blood Mononuclear Cell; Rest; Role; T-Lymphocyte; Telomerase; Telomere Shortening; Vaccines; cell type; follow-up; in vivo; monocyte; telomere

Telomere and telomerase are a key factors that regulate cell replicative lifespan. Telomere shortening has been observed in many types of cells in vitro and in cross-sectional analyses, and significantly shortened telomeres induce cell senescence and apoptosis. However, it remains to be determined how telomere length change in vivo and whether shortened telomeres contribute to age-associated decline of function. Telomerase is an enzyme that synthesizes telomere and is highly regulated in lymphocyte activation. To understand the in vivo change of telomere length and telomerase activity, we followed 200 participants (age range at the entry from 21 to 91) from the Baltimore Longitudinal Study of Aging (BLSA) over an average of five years and analyzed telomere length, telomerase activity, lymphocyte composition and health conditions in peripheral blood lymphocytes and monocytes at the beginning and five-year follow-up. We found that in PBMC, lymphocytes, and monocytes, telomere length decreased in 37%, did not change in 52%, and increased in 11% of the participants. Telomerase activity declined with age in resting and activated T cells, and resting but not activated B cells. Percentages of nave T cells decreased and CD28- T cells increased with age throughout the adult life and were positively and negatively correlated to telomere length in T cells, respectively. Finally, a significant portion of the observed telomere attrition with aging was explained by declined telomerase activity, decreased nave cells, increased CD28- T cells, and the presence of specific health conditions (cancer and adiposity). Together, our findings suggest that changes of telomere length, telomerase activity, and composition of subsets in blood lymphocytes in vivo with age are highly coordinated and influenced by health conditions.

端粒和端粒酶是调节细胞复制寿命的关键因素。 在体外和横截面分析中，在许多类型的细胞中都观察到了端粒缩短，并且明显缩短了端粒诱导细胞衰老和凋亡。但是，端粒长度在体内的变化以及缩短的端粒是否有助于与年龄相关的功能下降有待确定。 端粒酶是合成端粒的酶，在淋巴细胞激活中受到高度调节。 为了了解端粒长度和端粒酶活性的体内变化，我们在平均五年内从巴尔的摩衰老纵向研究（BLSA）进行了200名参与者（年龄范围为21至91岁），并分析了端粒长度，远距离酶活性的长度，远距离酶活性，淋巴细胞组合和健康状况的围裙及其五年级的次要症状和健康。我们发现，在PBMC，淋巴细胞和单核细胞中，端粒长度降低了37％，没有变化52％，而11％的参与者则增加。端粒酶活性随着静息和活化的T细胞的年龄而下降，静止而不是激活的B细胞。在整个成人生活中，中殿T细胞的百分比降低，CD28-T细胞随着年龄的增长而增加，并且分别与T细胞的端粒长度呈正相关。最后，观察到的端粒损耗的很大一部分是通过端粒酶活性下降，中殿细胞降低，CD28-T细胞增加以及特定健康状况（癌症和肥胖）的存在来解释的。 总之，我们的发现表明，随着年龄的增长，体内血液淋巴细胞中端粒长度，端粒酶活性和子集的组成的变化受到健康状况的高度协调和影响。