Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians
Publication in refereed journal


摘要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.
著者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 NLS, Wang XF, Zhou J, Cai WW, He YH, Kong QP
期刊名稱Genome Research
頁次1601 - 1610

上次更新時間 2021-27-02 於 02:04