State Key Laboratory of Genetic Resources and Evolution/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China.
Genome Res. 2018 Nov;28(11):1601-1610. doi: 10.1101/gr.220780.117. Epub 2018 Oct 23.
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, , , , and , could promote autophagy and delay senescence in cultured IMR-90 cells, while overexpression of the homolog of , , 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 to humans.
百岁老人（CENs）是研究人类长寿和健康衰老机制的理想对象。在这里，我们通过 RNA 测序分析了 76 名百岁老人、54 名百岁老人的子女和 41 名百岁老人子女的配偶的转录组，发现 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。该途径的几个基因的过表达， ， ， ，和 ，可促进 IMR-90 细胞中的自噬并延缓衰老，而 的同源物 ， ，则可延长转基因果蝇的寿命。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，表现为自噬编码基因和血清 beclin 1（BECN1）水平升高。鉴于自噬溶酶体功能随年龄正常下降，这些发现为我们的样本存在性别偏倚的情况下，至少在女性 CENs 中实现长寿提供了一个有说服力的解释，并表明通过自噬增强废物清除活性可能是一种保守机制，可以延长从 到人类的寿命。
