Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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, NL-S; Wang, X-F; Zhou, J; Cai, W-W; He, Y-H; Kong, Q-P

Published Date

  • November 2018

Published In

Volume / Issue

  • 28 / 11

Start / End Page

  • 1601 - 1610

PubMed ID

  • 30352807

Pubmed Central ID

  • PMC6211641

Electronic International Standard Serial Number (EISSN)

  • 1549-5469

Digital Object Identifier (DOI)

  • 10.1101/gr.220780.117


  • eng

Conference Location

  • United States