Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians

• Published in: Genome research Vol. 28; no. 11; pp. 1601 - 1610
• Main Authors: Xiao, Fu-Hui, Chen, Xiao-Qiong, Yu, Qin, Ye, Yunshuang, Liu, Yao-Wen, Yan, Dongjing, Yang, Li-Qin, Chen, Guijun, Lin, Rong, Yang, Liping, Liao, Xiaoping, Zhang, Wen, Zhang, Wei, Tang, Nelson Leung-Sang, Wang, Xiao-Fan, Zhou, Jumin, Cai, Wang-Wei, He, Yong-Han, Kong, Qing-Peng
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.11.2018
• Subjects: Aged; Aged, 80 and over; Aging; Autophagy; Autophagy - genetics; Autophagy-Related Proteins - genetics; Autophagy-Related Proteins - metabolism; Beclin-1 - genetics; Beclin-1 - metabolism; Cathepsin B - genetics; Cathepsin B - metabolism; Centenarians; Children; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; Drosophila; Female; Gene expression; Geriatrics; Humans; Insects; Life span; Longevity; Longevity - genetics; Lysosomes - metabolism; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Middle Aged; Oldest old people; Phagocytosis; Ribonucleic acid; RNA; Senescence; Transcriptome; Vacuolar Proton-Translocating ATPases - genetics; Vacuolar Proton-Translocating ATPases - metabolism
• ISSN: 1088-9051; 1549-5469; 1549-5469
• DOI: 10.1101/gr.220780.117

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.