Survey of senescent cell markers with age in human tissues
Survey of senescent cell markers with age in human tissues
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DOI：
10.18632/aging.102903
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发表时间：
2020-03-15
期刊：
影响因子：
5.2
通讯作者：
Gorospe, Myriam
中科院分区：
文献类型：
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作者：
Idda, M. Laura;McClusky, Waverly G.;Gorospe, Myriam
由亚致死损伤引发的细胞衰老的特征在于无限期生长停滞、基因表达模式改变和衰老相关的分泌表型。虽然衰老过程中衰老细胞的积累会降低组织功能并促进许多与年龄相关的疾病，但目前还没有通用的标记物来检测组织中的衰老细胞。细胞周期蛋白依赖性激酶抑制剂2A（p16/CDKN 2A）和1A（p21/CDKN 1A）可以识别衰老细胞，但很少有研究检查表达这些标志物的细胞数量在不同器官中作为年龄的函数。在这里，我们系统地研究了组织阵列中的p16和p21阳性细胞，这些组织阵列旨在包括来自不同年龄段的人的正常器官。随着供体年龄的增加，在皮肤（表皮），胰腺和肾脏中发现p21阳性和p16阳性细胞的数量增加，而在大脑皮层，肝脏，脾脏和肠（结肠）中p16表达细胞增加，皮肤（真皮）中p21表达细胞增加。肺组织中表达p16或p21的细胞数量不随年龄变化，肌肉中也没有p21或p16阳性细胞。总之，不同的器官显示不同水平的衰老蛋白p16和p21作为整个人类寿命的年龄的函数。
Cellular senescence, triggered by sublethal damage, is characterized by indefinite growth arrest, altered gene expression patterns, and a senescence-associated secretory phenotype. While the accumulation of senescent cells during aging decreases tissue function and promotes many age-related diseases, at present there is no universal marker to detect senescent cells in tissues. Cyclin-dependent kinase inhibitors 2A (p16/CDKN2A) and 1A (p21/CDKN1A) can identify senescent cells, but few studies have examined the numbers of cells expressing these markers in different organs as a function of age. Here, we investigated systematically p16- and p21-positive cells in tissue arrays designed to include normal organs from persons across a broad spectrum of ages. Increased numbers of p21-positive and p16-positive cells with donor age were found in skin (epidermis), pancreas, and kidney, while p16-expressing cells increased in brain cortex, liver, spleen and intestine (colon), and p21-expressing cells increased in skin (dermis). The numbers of cells expressing p16 or p21 in lung did not change with age, and muscle did not appear to have p21- or p16positive cells. In summary, different organs display different levels of the senescent proteins p16 and p21 as a function of age across the human life span.