Young plasma reverses age-dependent alterations in hepatic function through the restoration of autophagy.

Young plasma reverses age-dependent alterations in hepatic function through the restoration of autophagy.
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年轻血浆通过恢复自噬逆转肝功能的年龄依赖性改变

DOI:
10.1111/acel.12708
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发表时间:
2018-03
期刊:
影响因子:
7.8
通讯作者:
Fang H
Fang H
中科院分区:
生物学1区
文献类型:
--
作者:
Liu A;Guo E;Yang J;Yang Y;Liu S;Jiang X;Hu Q;Dirsch O;Dahmen U;Zhang C;Gewirtz DA;Fang H

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最近的研究表明,年轻血液对衰老相关的器官退化有治疗作用,这表明年轻血液可以解决与老年相关的临床问题。鉴于有缺陷的自噬与衰老和衰老相关的器官损伤有关,本研究旨在确定年轻血液对衰老诱导的肝功能改变的影响及其潜在机制,重点关注自噬。老龄大鼠(22个月)每周3次,从幼龄大鼠(3个月)或老龄大鼠身上收集血浆(1 ml,静脉注射),连续4周,并用3 -甲基腺嘌呤或wortmannin抑制幼龄大鼠血液诱导的自噬。衰老与部分肝切除术后丙氨酸转氨酶和天冬氨酸转氨酶水平升高、脂褐素积累、脂肪变性、纤维化和肝脏再生缺陷有关,而年轻血浆注射可显著减轻这些症状。年轻血浆也可以恢复衰老受损的自噬活性。抑制年轻血浆恢复的自噬活性消除了年轻血浆对衰老肝损伤的有益作用。在体外实验中,年轻血清对衰老肝细胞具有保护作用,3 -甲基腺嘌呤、wortmannin或自噬相关蛋白7的小干扰RNA可减弱年轻血清的抗衰老作用。总的来说,我们的数据表明,年轻血浆可以通过恢复自噬来部分改善肝功能的年龄依赖性改变。
Recent studies showing the therapeutic effect of young blood on aging‐associated deterioration of organs point to young blood as the solution for clinical problems related to old age. Given that defective autophagy has been implicated in aging and aging‐associated organ injuries, this study was designed to determine the effect of young blood on aging‐induced alterations in hepatic function and underlying mechanisms, with a focus on autophagy. Aged rats (22 months) were treated with pooled plasma (1 ml, intravenously) collected from young (3 months) or aged rats three times per week for 4 weeks, and 3‐methyladenine or wortmannin was used to inhibit young blood‐induced autophagy. Aging was associated with elevated levels of alanine transaminase and aspartate aminotransferase, lipofuscin accumulation, steatosis, fibrosis, and defective liver regeneration after partial hepatectomy, which were significantly attenuated by young plasma injections. Young plasma could also restore aging‐impaired autophagy activity. Inhibition of the young plasma‐restored autophagic activity abrogated the beneficial effect of young plasma against hepatic injury with aging. In vitro, young serum could protect old hepatocytes from senescence, and the antisenescence effect of young serum was abrogated by 3‐methyladenine, wortmannin, or small interfering RNA to autophagy‐related protein 7. Collectively, our data indicate that young plasma could ameliorate age‐dependent alterations in hepatic function partially via the restoration of autophagy.
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