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Genome Res. 2018 Nov;28(11):1601-1610. doi: 10.1101/gr.220780.117. Epub 2018 Oct 23.

Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians.

Xiao FH#1,2,3,4, Chen XQ#1,2,3,4, Yu Q#1,2,3,5,4, Ye Y#5,6, Liu YW1,2,3,5,4, Yan D7, Yang LQ1,2,3,4, Chen G6, Lin R8, Yang L6, Liao X9, Zhang W7, Zhang W5,6, Tang NL3,10, Wang XF11, Zhou J6, Cai WW7, He YH1,2,3,4, Kong QP1,2,3,4.

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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.
KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.
Kunming Key Laboratory of Healthy Aging Study, Kunming 650223, China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China.
Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou 571199, China.
Department of Biology, Hainan Medical College, Haikou 571199, China.
Department of Neurology, the First Affiliated Hospital of Hainan Medical College, Haikou 571199, China.
Department of Chemical Pathology and Laboratory for Genetics of Disease Susceptibility, Li Ka Shing Institute of Health Sciences, and School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China.
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Contributed equally


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.

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