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1. Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1

Author

Karla A. Mark, Kathleen J. Dumas, Dipa Bhaumik, Birgit Schilling, Sonnet Davis, Tal Ronnen Oron, Dylan J. Sorensen, Mark Lucanic, Rachel B. Brem, Simon Melov, Arvind Ramanathan, Bradford W. Gibson, and Gordon J. Lithgow

Subjects
Biology (General), QH301-705.5
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

Published
2016
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2. Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1

Author

Sonnet S. Davis, Dylan J. Sorensen, Gordon J. Lithgow, Karla A. Mark, Birgit Schilling, Tal Ronnen Oron, Mark Lucanic, Kathleen J. Dumas, Arvind Ramanathan, Rachel B. Brem, Simon Melov, Dipa Bhaumik, and Bradford W. Gibson

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
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

Published
2016
Full Text
View/download PDF

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