Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes.
Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes.
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发表时间：
1993-04
影响因子：
9.8
通讯作者：
H. Vaziri;Franpois Schachter;I. Uchida;Lan Weit Xiaoming Zhu;R. Effros;Daniel;Cohen;C. Harley
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文献类型：
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作者：
H. Vaziri;Franpois Schachter;I. Uchida;Lan Weit Xiaoming Zhu;R. Effros;Daniel;Cohen;C. Harley
细胞衰老的端粒假说提出，人类染色体端粒DNA （TTAGGG）的丢失可能最终导致复制衰老过程中细胞周期退出。由于淋巴细胞具有有限的复制能力，并且由于血细胞在体内衰老过程中丢失了端粒DNA，我们希望确定：(a)加速的端粒丢失是否与唐氏综合征（DS）患者淋巴细胞的过早免疫衰老有关；(b)在体外淋巴细胞衰老过程中端粒DNA是否也丢失了。为了研究衰老和21三体对体内端粒丢失的影响，我们从140例（0-107岁）患者的外周血淋巴细胞中分离出基因组DNA，其中包括21例（0-45岁）退行性痴呆患者。用限制性内切酶HinfI和RsaI酶切产生末端限制性内切片段（TRFs），用端粒特异性探针（32P-(C3TA2)3）进行Southern分析检测。端粒损失率是根据平均后端区长度的减少作为供体年龄的函数来计算的。与年龄匹配的对照组（41 +/- 7.7 bp/年）相比，随供体年龄变化的DS患者端粒丢失率（133 +/- 15 bp/年）显著高于年龄匹配的对照组（41 +/- 7.7 bp/年）（P < .0005），提示端粒加速丢失是DS患者免疫早衰的生物标志物，并可能在这一过程中发挥作用。计算4个正常个体的淋巴细胞在体外衰老过程中的端粒损失，培养10-30倍群体。端粒丢失的速率约为120 bp/细胞加倍，与其他体细胞相当。（摘要删节250字）
The telomere hypothesis of cellular aging proposes that loss of telomeric DNA (TTAGGG) from human chromosomes may ultimately cause cell-cycle exit during replicative senescence. Since lymphocytes have a limited replicative capacity and since blood cells were previously shown to lose telomeric DNA during aging in vivo, we wished to determine: (a) whether accelerated telomere loss is associated with the premature immunosenescence of lymphocytes in individuals with Down syndrome (DS) and (b) whether telomeric DNA is also lost during aging of lymphocytes in vitro. To investigate the effects of aging and trisomy 21 on telomere loss in vivo, genomic DNA was isolated from peripheral blood lymphocytes of 140 individuals (age 0-107 years), including 21 DS patients (age 0-45 years). Digestion with restriction enzymes HinfI and RsaI generated terminal restriction fragments (TRFs), which were detected by Southern analysis using a telomere-specific probe (32P-(C3TA2)3). The rate of telomere loss was calculated from the decrease in mean TRF length, as a function of donor age. DS patients showed a significantly higher rate of telomere loss with donor age (133 +/- 15 bp/year) compared with age-matched controls (41 +/- 7.7 bp/year) (P < .0005), suggesting that accelerated telomere loss is a biomarker of premature immunosenescence of DS patients and that it may play a role in this process. Telomere loss during aging in vitro was calculated for lymphocytes from four normal individuals, grown in culture for 10-30 population doublings. The rate of telomere loss was approximately 120 bp/cell doubling, comparable to that seen in other somatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)