Vitamin D and Healthy Aging: Establishing the Sled Dog Sentinel for the Circumpolar North

维生素 D 与健康老龄化：为北极圈建立雪橇犬哨兵

• 批准号: 10649356
• 负责人: Kriya L Dunlap
• 金额: $ 7.75万
• 依托单位: UNIVERSITY OF ALASKA FAIRBANKS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649356
• 关键词: Adoption; Affect; Age; Aging; Alaska; Alaska Native; Alaskan; Animal Model; Arctic Regions; Biochemical Pathway; Biological Markers; Biomedical Research; Brain; Canis familiaris; Child; Chronology; Coin; Consensus; Consumption; Custom; Data; Dementia; Diabetes Mellitus; Diet; Dietary Intervention; Dietary Supplementation; Dietary intake; Disease; Diurnal Rhythm; Eating; Economics; Elderly; Exercise; Exhibits; Fishes; Food; GLUT 4 protein; Glucose Transporter; Goals; Health; Hormones; Human; Impaired cognition; Impairment; Indigenous; Insulin; Insulin Resistance; Intake; Intervention Studies; Inuits; Knowledge; Laboratory Animals; Life Style; Ligands; Link; Longevity; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Metabolic; Metabolic Diseases; Metabolic Marker; Metabolic syndrome; Modeling; Morphology; Neurodegenerative Disorders; North America; Nutrient; Nutritional; Outcome; Oxidative Stress; Peripheral Blood Mononuclear Cell; Persons; Play; Polyunsaturated Fatty Acids; Population; Prevalence; Process; Production; Public Health; Recommendation; Reporting; Research; Rickets; Risk; Risk Factors; Role; Rural; Salmon; Sample Size; Seasonal Variations; Sentinel; Serum; Skin; Sledding; Societies; Source; Sun Exposure; Sunlight; Tissues; UV Radiation Exposure; Vitamin D; Vitamin D Deficiency; Vitamin D3 Receptor; Yup' ik; age effect; aging brain; brain health; canine model; experience; gray matter; gut health; healthy aging; high risk; immune function; improved; inflammatory marker; insulin signaling; metabolic rate; prevent; prohormone; response; transcription factor; trend; western diet; white matter

PROJECT SUMMARY Our long-term goal is to establish levels of vitamin D intake and vitamin D sufficiency for humans and canines living in the circumpolar north. Our overall objectives are to (i) define how chronological age impacts vitamin D status and morphological changes in the sled dog model, and (ii) determine the effects of salmon on vitamin D status and markers of metabolic syndrome and insulin signaling in old and young sled dogs. With their shorter lifespan and parallel biochemical pathways, dogs have become an important biomedical research model for both dementia related impairments and insulin signaling. Sled dogs, in particular, are an important human health model in the circumpolar north because they are part of the traditional subsistence lifestyle. Over the past 100 years, societies in North America and elsewhere in the world have transitioned towards the so-called “Western diet,” composed primarily of highly processed “factory foods”. This nutritional transition has been identified as playing a central role in current public health issues in peoples of the far north. Historically, Alaska Natives (AN) were able to consume adequate vitamin D from traditional foods, most notably from salmon, despite living at latitudes that prevent the synthesis of vitamin D in the skin from sunlight for much of the year. This is also true for village sled dogs. With the shift away from traditional foods, peoples of the circumpolar north are experiencing increased prevalence of vitamin D deficiency. Yup’ik children are developing rickets at higher rates while elders consistently exhibit higher serum vitamin D levels; this is a stark contrast to national trends. It is estimated that over 1 billion people worldwide are deficient in vitamin D. Vitamin D deficiency has been implicated in a multitude of diseases, including metabolic disorders, aging, and cognitive impairments. Still, little consensus has been reached on recommended intake to achieve adequate levels in humans and even less so in dogs. Therefore, there is a critical need to develop better understanding of vitamin D intake in the circumpolar north, where there is the highest risk of deficiency, to understand the links between diet, age, vitamin D status, and metabolic health. This study will begin to fill the gaps in knowledge pertaining to vitamin D deficiency with the following specific aims: 1) Correlate markers of brain aging with vitamin D status in an animal model of the circumpolar north and 2) Determine the effects of increased vitamin D from wild Alaska salmon on biomarkers of insulin signaling and metabolic health. Volume and morphology changes in brain gray and white matter will be assessed with magnetic resonance imaging in old and young dogs and correlated with serum vitamin D status. In addition to other markers of metabolic syndrome, the insulin responsive glucose transporter (GLUT4) on peripheral blood mononuclear cells will be measured in response to insulin in sled dogs of varying ages before and after a dietary supplementation with wild Alaskan Salmon. The expected outcomes of this project will lend to the insufficient data pertaining to vitamin D requirements, status, and health outcomes in populations that rely solely on dietary intake to obtain sufficiency.

项目摘要 我们的长期目标是为人类和犬类建立维生素D摄入量和维生素D的水平 生活在北极北方。我们的总体目标是（i）定义年代年龄如何影响维生素D 雪橇犬模型的状态和形态变化，（ii）确定鲑鱼对维生素D的影响 老年和雪橇犬的代谢综合征和胰岛素信号传导的状态和标记。他们短 寿命和平行生化途径，狗已成为重要的生物医学研究模型 痴呆症相关的损伤和胰岛素信号传导。尤其是雪橇犬是重要的人 北极北部的健康模型是因为它们是传统生存生活方式的一部分。在 过去100年，北美和世界其他地方的社会已经过渡到所谓的 “西方饮食”，主要由高度加工的“工厂食品”组成。这种营养过渡已经 被确定为在遥远北部人民的当前公共卫生问题中发挥核心作用。从历史上看，阿拉斯加 当地人（an）能够从传统食品中食用足够的维生素D，尤其是来自鲑鱼， 尽管生活在纬度上，这些纬度可以防止一年中大部分时间从阳光下从阳光下合成维生素D。 乡村雪橇犬也是如此。随着传统食品的转变，电路的人们 北部正在经历维生素D缺乏症的患病率增加。 Yup’ik的孩子正在开发风险集 较高的速度，而长者始终暴露出更高的血清维生素D水平；这与国家形成鲜明对比 趋势。据估计，全世界有超过10亿人缺乏维生素D。维生素D缺乏症已有 与多种疾病有关，包括代谢性疾病，衰老和认知障碍。 尽管如此，在推荐摄入方面几乎没有达成共识，以达到人类的足够水平和 在狗中甚至少了。因此，迫切需要更好地了解维生素D的摄入 北极极北，那里有最高的缺乏风险，以了解饮食，年龄，年龄， 维生素D状态和代谢健康。这项研究将开始填补与维生素有关的知识的空白 D缺乏以下特定目的：1）将脑衰老的标记与维生素D状态相关联 北极极向北的动物模型和2）确定野生维生素D增加的影响 阿拉斯加鲑鱼对胰岛素信号传导和代谢健康的生物标志物。体积和形态 脑灰色和白质的变化将通过老年和年轻的磁共振成像进行评估 狗并与血清维生素D状态相关。除了代谢综合征的其他标记外， 胰岛素反应型葡萄糖转运蛋白（GLUT4）在外周血单核细胞上将测量 在饮食中补充野生阿拉斯加之前和之后，对各种年龄段不同年龄段胰岛素的胰岛素反应 三文鱼。该项目的预期结果将使与维生素D有关的数据不足 人群中仅依靠饮食摄入以获得足够的人群的要求，状态和健康结果。