Anti-aging treatments slow propagation of synucleinopathy by restoring lysosomal function

Dong Kyu Kim, Hee Sun Lim, Ichiro Kawasaki, Yhong Hee Shim, Nishant Vaikath, Omar Ali El-Agnaf, He Jin Lee, Seung Jae Lee

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Aging is the major risk factor for neurodegenerative diseases that are also associated with impaired proteostasis, resulting in abnormal accumulation of protein aggregates. However, the role of aging in development and progression of disease remains elusive. Here, we used Caenorhabditis elegans models to show that aging-promoting genetic variations accelerated the rate of cell-to-cell transmission of SNCA/α-synuclein aggregates, hallmarks of Parkinson disease, and the progression of disease phenotypes, such as nerve degeneration, behavioral deficits, and reduced life span. Genetic and pharmacological anti-aging manipulations slowed the spread of aggregates and the associated phenotypes. Lysosomal degradation was significantly impaired in aging models, while anti-aging treatments reduced the impairment. Transgenic expression of hlh-30p::hlh-30, the master controller of lysosomal biogenesis, alleviated intercellular transmission of aggregates in the aging model. Our results demonstrate that the rate of aging closely correlates with the rate of aggregate propagation and that general anti-aging treatments can slow aggregate propagation and associated disease progression by restoring lysosomal function.

Original languageEnglish
Pages (from-to)1849-1863
Number of pages15
JournalAutophagy
Volume12
Issue number10
DOIs
Publication statusPublished - 2 Oct 2016

Fingerprint

Disease Progression
Synucleins
Phenotype
Nerve Degeneration
Caenorhabditis elegans
Neurodegenerative Diseases
Parkinson Disease
Pharmacology
Protein Aggregates

Keywords

  • aggregate propagation
  • aging
  • bimolecular fluorescence complementation
  • C. elegans
  • lysosome
  • Parkinson disease
  • SNCA/α-synuclein

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Anti-aging treatments slow propagation of synucleinopathy by restoring lysosomal function. / Kim, Dong Kyu; Lim, Hee Sun; Kawasaki, Ichiro; Shim, Yhong Hee; Vaikath, Nishant; Ali El-Agnaf, Omar; Lee, He Jin; Lee, Seung Jae.

In: Autophagy, Vol. 12, No. 10, 02.10.2016, p. 1849-1863.

Research output: Contribution to journalArticle

Kim, Dong Kyu ; Lim, Hee Sun ; Kawasaki, Ichiro ; Shim, Yhong Hee ; Vaikath, Nishant ; Ali El-Agnaf, Omar ; Lee, He Jin ; Lee, Seung Jae. / Anti-aging treatments slow propagation of synucleinopathy by restoring lysosomal function. In: Autophagy. 2016 ; Vol. 12, No. 10. pp. 1849-1863.
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