Unidad de Investigación en Epidemiología Clínica, Unidad Médica de Alta Especialidad (UMAE) No, 1 Bajío, Instituto Mexicano del Seguro Social (IMSS), León, Guanajuato, Mexico.
BMC Geriatr. 2013 Sep 24;13:99. doi: 10.1186/1471-2318-13-99.
Recently, a direct correlation with telomere length, proliferative potential and telomerase activity has been found in the process of aging in peripheral blood cells. The objective of the study was to evaluate telomere length and proliferative potential in peripheral blood mononuclear cells (PBMCs) after stimulation with Concanavalin A (ConA) of young adults compared with older adults.
Blood samples were obtained from 20 healthy young males (20-25 years old) (group Y) and 20 males (60-65 years old) (group O). We compared PBMC proliferation before and after stimulation with ConA. DNA was isolated from cells separated before and after culture with ConA for telomeric measurement by real-time polymerase chain reaction.
In vitro stimulation of PBMCs from young subjects induced an increase of telomere length as well as a higher replicative capacity of cell proliferation. Samples from older adults showed higher loss of telomeric DNA (p = 0.03) and higher levels of senescent (≤6.2 kb) telomeric DNA (p = 0.02) and displayed a marked decrease of proliferation capacity. Viability cell counts and CFSE tracking in 72-h-old cell cultures indicated that group O PBMCs (CD8+ and CD4+ T cells) underwent fewer mitotic cycles and had shorter telomeres than group Y (p = 0.04).
Our findings confirm that telomere length in older-age adults is shorter than in younger subjects. After stimulation with ConA, cells are not restored to the previous telomere length and undergo replicative senescence. This is in sharp contrast to the response observed in young adults after ConA stimulation where cells increase in telomere length and replicative capacity. The mechanisms involved in this phenomenon are not yet clear and merit further investigation.
最近,在衰老过程中,外周血中的端粒长度、增殖潜能和端粒酶活性之间存在直接相关性。本研究旨在评估年轻成年人和老年人外周血单个核细胞(PBMC)经刀豆蛋白 A(ConA)刺激后的端粒长度和增殖潜能。
从 20 名健康的年轻男性(20-25 岁)(Y 组)和 20 名男性(60-65 岁)(O 组)中获得血液样本。我们比较了 ConA 刺激前后 PBMC 的增殖情况。从细胞培养前和培养后的细胞中分离出 DNA,通过实时聚合酶链反应测量端粒长度。
体外刺激年轻受试者的 PBMC 可诱导端粒长度增加以及细胞增殖的复制能力增强。老年组的样本显示出更高的端粒 DNA 丢失(p = 0.03)和更高水平的衰老(≤6.2 kb)端粒 DNA(p = 0.02),并显示出增殖能力的明显下降。72 小时龄细胞培养中的细胞活力计数和 CFSE 追踪表明,O 组的 PBMC(CD8+和 CD4+T 细胞)经历的有丝分裂周期较少,端粒较短,与 Y 组相比(p = 0.04)。
我们的发现证实,老年人群的端粒长度比年轻人群更短。在 ConA 刺激后,细胞不能恢复到之前的端粒长度并经历复制性衰老。这与 ConA 刺激后年轻成年人观察到的细胞端粒长度和复制能力增加的反应形成鲜明对比。涉及这种现象的机制尚不清楚,值得进一步研究。