Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians

  1. Qing-Peng Kong1,2,4,7
  1. 1State 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;
  2. 2Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China;
  3. 3Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou 571199, China;
  4. 4KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China;
  5. 5Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China;
  6. 6Key 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;
  7. 7Kunming Key Laboratory of Healthy Aging Study, Kunming 650223, China;
  8. 8Department of Biology, Hainan Medical College, Haikou 571199, China;
  9. 9Department of Neurology, the First Affiliated Hospital of Hainan Medical College, Haikou 571199, China;
  10. 10Department 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;
  11. 11Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
  1. 12 These authors contributed equally to this work.

  • Corresponding authors: kongqp{at}mail.kiz.ac.cn, heyonghan{at}mail.kiz.ac.cn, caiww591020{at}163.com, zhoujm{at}mail.kiz.ac.cn
  • Abstract

    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.

    Footnotes

    • Received January 18, 2017.
    • Accepted October 3, 2018.

    This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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