de Jonge Hendrik J M, Woolthuis Carolien M, de Bont Eveline S J M, Huls Gerwin
Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Aging (Albany NY). 2009 Oct 23;1(11):949-53. doi: 10.18632/aging.100096.
Aging is generally considered to be the consequence of stem cell attrition caused by the activity of tumor suppressor pathways that censor potentially malignant clones by eliciting apoptosis or senescence. An important effector of aging is the cyclindependent kinase inhibitor p16(INK4a), which is also a known suppressor of cancer. The expression of p16(INK4a) is very low or absent in young organisms but increases with advancing age. We recently showed that, unlike healthy cells, acute myeloid leukemia (AML) derived blasts show a down-regulation of p16(INK4a) mRNA with increasing age. Based on this observation we hypothesize that suppression of defense mechanisms which protect older cells against cellular and DNA damage might facilitate oncogenesis in older individuals.
衰老通常被认为是肿瘤抑制通路活动导致干细胞损耗的结果，这些通路通过引发凋亡或衰老来审查潜在的恶性克隆。衰老的一个重要效应因子是细胞周期蛋白依赖性激酶抑制剂p16(INK4a)，它也是一种已知的癌症抑制因子。p16(INK4a)在年轻生物体中的表达非常低或不存在，但随着年龄的增长而增加。我们最近发现，与健康细胞不同，急性髓系白血病（AML）来源的原始细胞随着年龄的增长p16(INK4a) mRNA表达下调。基于这一观察结果，我们推测，保护老年细胞免受细胞和DNA损伤的防御机制受到抑制，可能会促进老年个体的肿瘤发生。
