Nature和Cell子刊:男性为何比女性寿命短?Y染色体缺失来解答

2016-05-25 佚名 生物探索

女性寿命普遍比男性长,这似乎已被广泛接受,并成为一种常识。然而,导致男女寿命差异的机制和危险因素在很大程度上还是未知。瑞典乌普萨拉大学的研究人员认为Y染色体缺失是男女寿命差异的原因之一,相关结论发表在《美国人类遗传学杂志》和《Nature Genetics》上。


女性寿命普遍比男性长,这似乎已被广泛接受,并成为一种常识。据世界卫生组织,男性平均寿命比女性短5-10年。从第六次全国人口普查来看,2010年我国男性平均寿命为72.38岁,女性为77.37岁,男女的平均寿命差为4.99岁。

然而,导致男女寿命差异的机制和危险因素在很大程度上还是未知。2015年7月6日,南加州大学的研究人员在PNAS杂志上表示,进入21世纪后男性比女性寿命短的主要原因是男性更容易患心脏病。瑞典乌普萨拉大学的研究人员认为Y染色体缺失是男女寿命差异的原因之一,相关结论发表在《美国人类遗传学杂志》和《Nature Genetics》上。

Y染色体缺失与阿尔兹海默症相关

乌普萨拉大学的研究人员通过一项简单的阿尔兹海默症风险检测发现,血细胞中Y染色体缺失的男性患老年痴呆的风险更大,这与癌症一样增加死亡的风险,相关结果于5月23日发表在《美国人类遗传学杂志》上。

已知Y染色体缺失影响20%的80岁以上高龄男性,Y染色体缺失也是男性生命中最常见的基因突变。乌普萨拉大学免疫学、遗传协学和病例学系的两位教授Lars Forsberg 和Jan Dumanski及其同事分析了3200名男性的Y染色体缺失情况,受试者的平均年龄为73岁(37-96岁),结果发现17%的受试者血细胞中出现Y染色体缺失,且这种现象随年龄升高而显著,此外研究人员发现,阿尔兹海默症的发病率与Y染色体缺失有关,与健康人相比,阿尔兹海默症患者的Y染色体缺失程度更大,且Y染色体缺失可作为阿尔兹海默症发展的标志。

Y染色体缺失与癌症发展有关

在此之前,Lars Forsberg 和Jan Dumanski教授曾在《Nature Genetics》上发表研究揭示了血细胞中的Y染色体缺失与寿命短和其他器官的癌症死亡率有关。

细胞中的DNA突变累积与癌症及糖尿病等有关,在该研究中,研究人员分析了1600名老年男性的血液样本,结果发现最常见的遗传变化是白细胞中的Y染色体比例下降。由于这项研究横跨的时间较长,因而研究人员可以检测Y染色体的缺失与寿命之间的关联。

Lars Forsberg表示,“血细胞中Y染色体缺失的男性寿命更短,同时我们还检测了Y染色体缺失和癌症死亡率之间的关系。” Jan Dumanski表示,“也许你曾听别人说Y染色体很小,含有很少的遗传信息,但这并不正确,我们的研究表明Y染色体可能在肿瘤抑制过程中扮演重要的角色,这可能是男性患癌风险比女性高的原因。因而我们认为,将来Y染色体可能是预测男性癌症风险的通用标志物。”

男性寿命短或与Y染色体缺失有关,但需回答很多问题

在回顾这两项研究时,Lars Forsberg教授表示,“我在撰写首篇Y染色体缺失和非血液肿瘤发展的文章时,就滋生了关于Y染色体缺失与阿尔兹海默症的研究思路,在探索免疫监视作用的过程中,我发现该过程被广泛应用于阿尔兹海默症的研究,因此当时我就认为Y染色体缺失可能参与了阿尔兹海默症的发展。”

在这些研究中,研究人员通过标准的分子生物学技术鉴别了血细胞中的Y染色体缺失,这种现象在老年人血细胞中较为常见,在年轻男性中较少发生。研究人员表示,“由于女性没有Y染色体, Y染色体的缺失可能与男性短寿命有关,然而这种机制仍未得到正确理解。”

目前研究人员正在研究Y染色体缺失的功能影响,探讨其在不同人群中的影响差异以及Y染色体缺失还与哪些疾病有关,同时展开研究更好地了解哪些癌症与Y染色体缺失有关,确定Y染色体缺失能否作为阿尔兹海默症的早期发展信号,如是否与轻度认知障碍有关。

另一个需要回答的问题是血细胞中的Y染色体缺失如何与其他器官的疾病发展相关。Jan Dumanski 教授表示,“该研究中的血细胞参与了免疫系统,事实上,这些细胞中的Y染色体缺失与其他器官疾病的关联是很显著的,因此我们推测Y染色体缺失导致血细胞失去了一部分免疫功能。”

该研究团队的早前研究表明,吸烟大大加速Y染色体的缺失。然而,吸烟似乎是一个短暂的影响,并且具有剂量依赖性,因而戒烟可以扭转Y染色体的缺失,因此研究人员强调了戒烟的重要性。

Y染色体缺失或可作为疾病风险的通用标志物

另一个更难解决的问题是对严重疾病如阿尔兹海默症和癌症等的诊断和治疗。目前的诊断手段以临床症状为基础,发展早期诊断技术可能对重大疾病的治疗带来更好的效果。例如,将来Y染色体缺失或许能用来鉴定男性的疾病风险,并用来早期检测肿瘤或神经疾病的发展,此外Y染色体缺失还有望与其他生物标志物一起成为一种重要的诊断工具,用于多种疾病风险的预测。

Lars Forsberg表示,“在普通人群中检测Y染色体的缺失可为高危男性提供预防策略,例如我们可以预测哪些男性的癌症风险较高,并可以密切关注疾病的发展,采取适当的预防措施。总之,Y染色体缺失的广泛检测可从根本上降低男性的死亡率,甚至可能消除男女性寿命的差异。”

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    2016-11-22 liye789132251
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  4. 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createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuK9CDibOwszLoEBg36ZXqzB5NDasNV9GTfFDmBicM1V8hUS4OtTicG3IiaFIKq4wqD23LUxORRJXqjVs/0, createdBy=00e81647535, createdName=I come, createdTime=Thu May 26 09:30:00 CST 2016, time=2016-05-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=87159, encodeId=79e18e15994, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c891611001, createdName=medscc, createdTime=Wed May 25 16:48:00 CST 2016, time=2016-05-25, status=1, ipAttribution=)]
    2016-09-17 ylzr123

    点个赞!好文章有待学习探讨。

    0

  5. 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    2017-05-08 维他命
  6. 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  7. 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  8. 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createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuK9CDibOwszLoEBg36ZXqzB5NDasNV9GTfFDmBicM1V8hUS4OtTicG3IiaFIKq4wqD23LUxORRJXqjVs/0, createdBy=00e81647535, createdName=I come, createdTime=Thu May 26 09:30:00 CST 2016, time=2016-05-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=87159, encodeId=79e18e15994, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c891611001, createdName=medscc, createdTime=Wed May 25 16:48:00 CST 2016, time=2016-05-25, status=1, ipAttribution=)]
    2016-05-27 周虎
  9. 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createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuK9CDibOwszLoEBg36ZXqzB5NDasNV9GTfFDmBicM1V8hUS4OtTicG3IiaFIKq4wqD23LUxORRJXqjVs/0, createdBy=00e81647535, createdName=I come, createdTime=Thu May 26 09:30:00 CST 2016, time=2016-05-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=87159, encodeId=79e18e15994, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c891611001, createdName=medscc, createdTime=Wed May 25 16:48:00 CST 2016, time=2016-05-25, status=1, ipAttribution=)]
    2016-05-26 I come

    好思路,不错

    0

  10. 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createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Sat Sep 17 08:27:00 CST 2016, time=2016-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959649, encodeId=140619596499d, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, 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 May 08 09:50:00 CST 2017, time=2017-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1331616, encodeId=4e0e1331616ac, content=<a href='/topic/show?id=d85a6181e4d' target=_blank style='color:#2F92EE;'>#染色体#</a>, beContent=null, 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May 27 05:50:00 CST 2016, time=2016-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538845, encodeId=3ffd153884576, content=<a href='/topic/show?id=9f5a189918d' target=_blank style='color:#2F92EE;'>#Y染色体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18991, encryptionId=9f5a189918d, topicName=Y染色体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1fc213064778, createdName=周虎, createdTime=Fri May 27 05:50:00 CST 2016, time=2016-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=87248, encodeId=49598e248b1, content=好思路,不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuK9CDibOwszLoEBg36ZXqzB5NDasNV9GTfFDmBicM1V8hUS4OtTicG3IiaFIKq4wqD23LUxORRJXqjVs/0, createdBy=00e81647535, createdName=I come, createdTime=Thu May 26 09:30:00 CST 2016, time=2016-05-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=87159, encodeId=79e18e15994, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c891611001, createdName=medscc, createdTime=Wed May 25 16:48:00 CST 2016, time=2016-05-25, status=1, ipAttribution=)]
    2016-05-25 medscc

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