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Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1
- Source :
- Cell Reports, Vol 17, Iss 5, Pp 1227-1237 (2016)
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Summary: Vitamin D has multiple roles, including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases, including Alzheimer’s disease, Parkinson’s disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that vitamin-D3-induced lifespan extension requires the stress response pathway genes skn-1, ire-1, and xbp-1. Vitamin D3 (D3) induced expression of SKN-1 target genes but not canonical targets of XBP-1. D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented toxicity caused by human β-amyloid. Our observation that D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels and may explain why such a wide variety of human age-related diseases are associated with vitamin D deficiency. : Maintenance of protein homeostasis is crucial to cellular health and contributes significantly to the lifespan of organisms. Mark et al. demonstrate that vitamin D supplementation promotes protein homeostasis and slows aging in the nematode, C. elegans. These findings identify a mechanism by which vitamin D influences aging. Keywords: Ceanorhabditis elegans, vitamin D, lifespan. aging, insoluble protein, SKN-1, XBP-1, IRE-1, proteostasis, protein aggregation, Alzheimer’s disease
- Subjects :
- 0301 basic medicine
vitamin D
Disease
Protein aggregation
Endoplasmic Reticulum
chemistry.chemical_compound
0302 clinical medicine
Homeostasis
lcsh:QH301-705.5
Caenorhabditis elegans
Cholecalciferol
2. Zero hunger
biology
3. Good health
DNA-Binding Proteins
Alzheimer’s disease
Vitamin
medicine.medical_specialty
XBP-1
Longevity
lifespan. aging
Protein Serine-Threonine Kinases
General Biochemistry, Genetics and Molecular Biology
vitamin D deficiency
Article
protein aggregation
03 medical and health sciences
Protein Aggregates
SKN-1
Calcitriol
Stress, Physiological
Internal medicine
medicine
Vitamin D and neurology
Animals
Caenorhabditis elegans Proteins
Calcium metabolism
proteostasis
biology.organism_classification
medicine.disease
IRE-1
Ceanorhabditis elegans
030104 developmental biology
Proteostasis
Endocrinology
chemistry
lcsh:Biology (General)
Solubility
insoluble protein
Unfolded Protein Response
Carrier Proteins
030217 neurology & neurosurgery
Transcription Factors
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 17
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....3ca66f986cfc7ddfd5a47ee887eb7250
- Full Text :
- https://doi.org/10.1016/j.celrep.2016.09.086