Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians.
Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians.
复制标题
转录组证据显示百岁老人的自噬溶酶体功能增强
DOI：
10.1101/gr.220780.117
复制
发表时间：
2018-11
期刊：
影响因子：
7
通讯作者：
Kong QP
中科院分区：
文献类型：
--
作者：
Xiao FH;Chen XQ;Yu Q;Ye Y;Liu YW;Yan D;Yang LQ;Chen G;Lin R;Yang L;Liao X;Zhang W;Zhang W;Tang NL;Wang XF;Zhou J;Cai WW;He YH;Kong QP
百岁老人是研究人类长寿和健康衰老机制的优秀对象。在这里，我们通过RNA测序分析了76名百岁老人，54名百岁儿童和41名百岁儿童配偶的转录组，发现在CENs表现出的显著差异表达基因（SDEGs）中，自噬-溶酶体途径显著上调。来自该途径的几个基因CTSB，ATP 6V 0 C，ATG 4D和WIPI 1的过表达可以促进自噬并延迟培养的IMR-90细胞的衰老，而WIPI 1的果蝇同源物Atg 18 a的过表达延长了转基因果蝇的寿命。有趣的是，增强的自噬-溶酶体活性可以部分传递给它们的后代，正如它们更高水平的自噬编码基因和血清beclin 1（BECN 1）所证明的那样。鉴于自噬-溶酶体功能的正常年龄相关性下降，这些发现为至少在女性CEN中实现长寿提供了令人信服的解释，因为我们收集的样本中存在性别偏见，并表明通过自噬增强的废物清洁活性可能作为一种保守的机制来延长从果蝇到人类的寿命。
Centenarians (CENs) are excellent subjects to study the mechanisms of human longevity and healthy aging. Here, we analyzed the transcriptomes of 76 centenarians, 54 centenarian-children, and 41 spouses of centenarian-children by RNA sequencing and found that, among the significantly differentially expressed genes (SDEGs) exhibited by CENs, the autophagy-lysosomal pathway is significantly up-regulated. Overexpression of several genes from this pathway, CTSB, ATP6V0C, ATG4D, and WIPI1, could promote autophagy and delay senescence in cultured IMR-90 cells, while overexpression of the Drosophila homolog of WIPI1, Atg18a, extended the life span in transgenic flies. Interestingly, the enhanced autophagy-lysosomal activity could be partially passed on to their offspring, as manifested by their higher levels of both autophagy-encoding genes and serum beclin 1 (BECN1). In light of the normal age-related decline of autophagy-lysosomal functions, these findings provide a compelling explanation for achieving longevity in, at least, female CENs, given the gender bias in our collected samples, and suggest that the enhanced waste-cleaning activity via autophagy may serve as a conserved mechanism to prolong the life span from Drosophila to humans.
登录
查看更多内容
DOI：
10.4161/15384101.2014.950151
发表时间：
2014
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
de Magalhães JP
通讯作者：
de Magalhães JP
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
7.8
作者：
Engberg H;Oksuzyan A;Jeune B;Vaupel JW;Christensen K
通讯作者：
Christensen K
影响因子：
5.4
作者：
Gershoni M;Pietrokovski S
通讯作者：
Pietrokovski S
影响因子：
64.5
作者：
Hofmann JW;Zhao X;De Cecco M;Peterson AL;Pagliaroli L;Manivannan J;Hubbard GB;Ikeno Y;Zhang Y;Feng B;Li X;Serre T;Qi W;Van Remmen H;Miller RA;Bath KG;de Cabo R;Xu H;Neretti N;Sedivy JM
通讯作者：
Sedivy JM