Telomere shortening is an in vivo marker of myocyte replication and aging

Telomere shortening is an in vivo marker of myocyte replication and aging
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DOI:
10.1016/s0002-9440(10)64949-8
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发表时间:
2000-03-01
影响因子:
6
通讯作者:
Anversa, P
Anversa, P
中科院分区:
医学2区
文献类型:
--
作者:
Kajstura, J;Pertoldi, B;Anversa, P

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为了确定成年心肌细胞是否能够多次分裂,以及这种生长形式是否仅限于随着年龄增长而保持这种能力的细胞亚群,我们测量了从胎儿和新生儿Fischer 344大鼠以及出生后4、12和27个月的大鼠左心室分离的心肌细胞核的端粒长度。两种独立的方法用于该分析:激光扫描细胞仪和共聚焦显微镜。在每种情况下,对端粒序列特异性肽核酸探针的荧光强度进行了评估。这两种技术产生了相似的结果。在占整个细胞群16%的肌细胞亚群中,端粒缩短随着年龄的增长而增加。在剩余的非分裂细胞中,衰老相关核蛋白p16(INK4)的逐渐积累得到了证实。总之,从出生到衰老,很大一部分心肌细胞反复分裂,抵消了衰老的哺乳动物大鼠心脏中细胞的持续死亡。
To determine whether adult cardiac myocytes are capable of multiple divisions and whether this form of growth is restricted to a subpopulation of cells that retain this capacity with age, telomere lengths were measured in myocyte nuclei isolated from the left ventricle of fetal and neonatal Fischer 344 rats and rats at 4, 12, and 27 months after birth. Two independent methodologies were used for this analysis: laser scanning cytometer and confocal microscopy. In each case, fluorescence intensity of a peptide nucleic acid probe specific for telomeric sequence was evaluated. The two techniques yielded comparable results. Telomeric shortening increased with age in a subgroup of myocytes that constituted 16% of the entire cell population. In the remaining nondividing cells, progressive accumulation of a senescent associated nuclear protein, p16(INK4), was evidenced. In conclusion, a significant fraction of myocytes divides repeatedly from birth to senescence, counteracting the continuous death of cells in the aging mammalian rat heart.