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Lysosome activity is modulated by multiple longevity pathways and is important for lifespan extension in C. elegans
- Source :
- eLife, eLife, Vol 9 (2020)
- Publication Year :
- 2020
- Publisher :
- eLife Sciences Publications, Ltd, 2020.
-
Abstract
- Lysosomes play important roles in cellular degradation to maintain cell homeostasis. In order to understand whether and how lysosomes alter with age and contribute to lifespan regulation, we characterized multiple properties of lysosomes during the aging process in C. elegans. We uncovered age-dependent alterations in lysosomal morphology, motility, acidity and degradation activity, all of which indicate a decline in lysosome function with age. The age-associated lysosomal changes are suppressed in the long-lived mutants daf-2, eat-2 and isp-1, which extend lifespan by inhibiting insulin/IGF-1 signaling, reducing food intake and impairing mitochondrial function, respectively. We found that 43 lysosome genes exhibit reduced expression with age, including genes encoding subunits of the proton pump V-ATPase and cathepsin proteases. The expression of lysosome genes is upregulated in the long-lived mutants, and this upregulation requires the functions of DAF-16/FOXO and SKN-1/NRF2 transcription factors. Impairing lysosome function affects clearance of aggregate-prone proteins and disrupts lifespan extension in daf-2, eat-2 and isp-1 worms. Our data indicate that lysosome function is modulated by multiple longevity pathways and is important for lifespan extension.
- Subjects :
- 0301 basic medicine
Proteases
insuin/igf-1 signaling
QH301-705.5
Science
Cell
Longevity
Motility
DAF-16/FOXO
SKN-1/NRF2
Biology
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Lysosome
medicine
Animals
Insulin
Biology (General)
Insulin-Like Growth Factor I
longevity pathways
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Transcription factor
Cathepsin
General Immunology and Microbiology
General Neuroscience
aging
General Medicine
Cell Biology
Receptor, Insulin
Cell biology
030104 developmental biology
medicine.anatomical_structure
lysosome
C. elegans
Medicine
Lysosomes
030217 neurology & neurosurgery
Homeostasis
Research Article
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....33b3193a714917c4df73c3bc99c8be20