Aging Cell:小分子保护转录应激稳态,延长寿命

2021-01-21 haibei MedSci原创

在这项工作的基础上,研究人员最近进一步表明,Maf-S的过度表达可以防止染色质可及性的丧失,并保持基因的反应性。

生物体的稳态依赖于一个复杂的细胞传感和反应机制网络,它维持着支持生命体的动态生化平衡。随着年龄的增长,这一系统的稳健性下降,导致对疾病的敏感性增加,对各种压力的耐受力下降,最终导致发病率和死亡率上升。衰老的生物体失去了感知相关变化或扰动,并动态调整生物功能的能力。

对环境和内部变化的适应依赖于能够动态调节生理功能的分子或细胞传感器、信号转导途径和效应器。虽然许多维持生物稳健性的动态平衡信号转导和反应途径已被很好地描述,但我们还不太清楚它们为什么以及如何随着生物体的衰老而降低其有效性。

已有的研究显示,对氧化应激或病原体等挑战的转录反应会随着年龄的增长而减弱。这种效应表现在应激反应转录因子Nrf2的功能下降。由果蝇Nrf2同源物CncC控制的保护性基因表达程序支持稳态和长寿。年龄相关的染色质变化使这些基因无法与CncC结合,并使它们在老年动物中对信号依赖性转录激活产生惰性。

已有的研究显示,CncC二聚体伴侣蛋白Maf-S的过度表达抵消了这种退化效应,并保护了生物体的健康。在这项工作的基础上,研究人员最近进一步表明,Maf-S的过度表达可以防止染色质可及性的丧失,并保持基因的反应性

此外,在整个成年期,通过药物诱导CncC靶基因的表达可以实现同样的结果,以及寿命的延长

因此,能够保持应激反应基因表达的药理或饮食干预可能是可行的抗衰老策略

 

原始出处:

Yang Cheng et al. Preserving transcriptional stress responses as an anti‐aging strategy. Aging Cell (2021). 

 

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    2021-04-28 宋威
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    2021-03-30 mjldent
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    2021-11-29 维他命
  5. [GetPortalCommentsPageByObjectIdResponse(id=1914714, encodeId=620d1914e1419, content=<a href='/topic/show?id=84d7469559b' target=_blank style='color:#2F92EE;'>#小分子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46955, encryptionId=84d7469559b, topicName=小分子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6105386, createdName=宋威, createdTime=Wed Apr 28 06:25:52 CST 2021, time=2021-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872132, encodeId=b2ec18e213268, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Jun 05 06:25:52 CST 2021, time=2021-06-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1747422, encodeId=e4a61e474224f, content=<a href='/topic/show?id=832e93345c3' target=_blank style='color:#2F92EE;'>#转录#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93345, encryptionId=832e93345c3, topicName=转录)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=58df35929710, createdName=mjldent, createdTime=Tue Mar 30 21:25:52 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962436, encodeId=df4d1962436e5, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Mon Nov 29 03:25:52 CST 2021, time=2021-11-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1646767, encodeId=605e1646e67f3, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Mon Apr 05 15:25:52 CST 2021, time=2021-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1445335, encodeId=24591445335c8, content=<a href='/topic/show?id=61e74928629' target=_blank style='color:#2F92EE;'>#应激#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49286, encryptionId=61e74928629, topicName=应激)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=79df5138909, createdName=ms1260584454294838, createdTime=Sat Jan 23 05:25:52 CST 2021, time=2021-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1479889, encodeId=f5a214e98898e, content=<a href='/topic/show?id=456b4954350' target=_blank style='color:#2F92EE;'>#延长寿命#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49543, encryptionId=456b4954350, topicName=延长寿命)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d9587588723, createdName=hittouch, createdTime=Sat Jan 23 05:25:52 CST 2021, time=2021-01-23, status=1, ipAttribution=)]
    2021-04-05 changfy
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