title: Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1.
abstract: 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.
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors: Karla A
authors: KA
authors: Mark
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA. Electronic address: kdumas@buckinstitute.org.
authors: Kathleen J
authors: KJ
authors: Dumas
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors: Dipa
authors: D
authors: Bhaumik
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors: Birgit
authors: B
authors: Schilling
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors: Sonnet
authors: S
authors: Davis
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors: Tal Ronnen
authors: TR
authors: Oron
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors: Dylan J
authors: DJ
authors: Sorensen
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors: Mark
authors: M
authors: Lucanic
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors: Rachel B
authors: RB
authors: Brem
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors: Simon
authors: S
authors: Melov
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors: Arvind
authors: A
authors: Ramanathan
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors: Bradford W
authors: BW
authors: Gibson
authors: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA. Electronic address: glithgow@buckinstitute.org.
authors: Gordon J
authors: GJ
authors: Lithgow
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002762:Cholecalciferol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D008136:Longevity / Q000502:physiology*; D066329:Protein Aggregates; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012995:Solubility; D013312:Stress, Physiological / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D056811:Unfolded Protein Response / Q000187:drug effects; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D066329:Protein Aggregates; D014157:Transcription Factors; C548541:XBP-1 protein, C elegans; D014807:Vitamin D; C073702:skn-1 protein, C elegans; D002762:Cholecalciferol; D017346:Protein Serine-Threonine Kinases; C541905:IRE-1 protein, C elegans; D002117:Calcitriol
keywords: Alzheimer’s disease; Ceanorhabditis elegans; IRE-1; SKN-1; XBP-1; insoluble protein; lifespan. aging; protein aggregation; proteostasis; vitamin D