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衰老是一种生理完整性丧失,功能受损,疾病和死亡风险增加的过程。早老症(HGPS)是一种加速化的衰老疾病,是研究人类正常衰老理想的疾病模型。由LMNA基因突变产生prelamin AΔ50在细胞内累积是造成早老症的主要原因,早老症病人表现出寿命急剧缩短,老化特征明显的现象,例如脱发、皮下脂肪减少、骨质疏松以及早逝。锌金属蛋白酶Zmpste24是prelamin A加工成为成熟lamin A蛋白的关键酶。敲除Zmpste24基因的小鼠表现出与早老症高度一致的衰老表型,同时也存在非常相似的发病机制,如染色质异常、DNA损伤和干细胞功能缺失等。Zmpste24缺失小鼠作为典型的早老模型小鼠因其衰老周期短,衰老特征明显而获得广泛应用。本文总结了以Zmpste24缺失早老小鼠为模型取得的早老相关分子机制的研究进展,以及抗衰老策略的最新发现。
Aging is a process of loss of physical integrity, impaired function, increased risk of disease and death. Premature Hypertension (HGPS) is an accelerated aging disease and a model of disease that is ideal for studying normal human aging. Production of prelamin by ΔNANA mutations AΔ50 accumulation in the cells is the major cause of premature aging. Patients with premature aging show a sharp reduction in life expectancy with significant signs of aging such as hair loss, subcutaneous fat loss, osteoporosis, and premature death. Zinc metalloproteinase Zmpste24 is the key enzyme that prelamin A processes into the mature lamin A protein. Mice knocked out of the Zmpste24 gene exhibit an aging phenotype that is highly consistent with premature aging, with very similar pathogenesis such as aberrant chromatin, DNA damage, and loss of stem cell function. Zmpste24-deficient mice have been widely used as typical early-aged mice because of their short aging cycle and obvious aging characteristics. This article summarizes the advances in the molecular mechanisms of premature aging acquired by Zmpste24-deficient premature and old mice as well as the recent findings of anti-aging strategies.