Xiao, F.H., Chen, X.Q., Yu, Q., Ye, Y., Liu, Y.W., Yan, D., Yang, L.Q., Chen, G., Lin, R., Yang, L., Liao, X., Zhang, W., Zhang, W., Tang, N.L., Wang, X.F., Zhou, J., Cai, W.W., He, Y.H., Kong, Q.P. (2018). Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians.  Genome Res. 28(11): 1601--1610.

FBrf0240487

Research paper

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.

PMC6211641 (PMC) (EuropePMC)