Carrasco-Garcia Estefania, Moreno Manuel, Moreno-Cugnon Leire, Matheu Ander
Cellular Oncology Group, Biodonostia Institute, San Sebastian, Spain.
Ikerbasque, Basque Foundation, Bilbao, Spain.
Aging Cell. 2017 Apr;16(2):219-225. doi: 10.1111/acel.12574. Epub 2017 Jan 19.
Arf/p53 pathway protects the cells against DNA damage induced by acute stress. This characteristic is the responsible for its tumor suppressor activity. Moreover, it regulates the chronic type of stress associated with aging. This is the basis of its anti-aging activity. Indeed, increased gene dosage of Arf/p53 displays elongated longevity and delayed aging. At a cellular level, it has been recently shown that increased dosage of Arf/p53 delays age-associated stem cell exhaustion and the subsequent decline in tissue homeostasis and regeneration. However, p53 can also promote aging if constitutively activated. In this context, p53 reduces tissue regeneration, which correlates with premature exhaustion of stem cells. We discuss here the current evidence linking the Arf/p53 pathway to the processes of aging and cancer through stem cell regulation.
Arf/p53通路保护细胞免受急性应激诱导的DNA损伤。这一特性是其肿瘤抑制活性的原因。此外，它调节与衰老相关的慢性应激类型。这是其抗衰老活性的基础。确实，Arf/p53基因剂量增加显示出寿命延长和衰老延迟。在细胞水平上，最近已表明Arf/p53剂量增加可延缓与年龄相关的干细胞耗竭以及随后组织稳态和再生能力的下降。然而，如果p53持续激活，它也可促进衰老。在这种情况下，p53会减少组织再生，这与干细胞过早耗竭相关。我们在此讨论目前将Arf/p53通路通过干细胞调节与衰老和癌症过程联系起来的证据。
