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.

项目总结 我们的长期目标是为人类和狗建立维生素D摄入量和维生素D充足水平 生活在环极地的北方。我们的总体目标是：(I)确定实际年龄对维生素D的影响 雪橇犬模型的状态和形态变化，以及(Ii)确定三文鱼对维生素D的影响 老年和年轻雪橇犬代谢综合征和胰岛素信号的状态和标志物。带着他们更短的 寿命和平行的生化途径，狗已经成为一个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。尤其是雪橇狗，是一种重要的人类 北极圈的健康模式，因为他们是传统的生存生活方式的一部分。超过了 在过去的100年里，北美和世界其他地方的社会已经向所谓的 “西式饮食”，主要由经过深度加工的“工厂食品”组成。这一营养转变一直是 被确定为在遥远北方人民当前的公共卫生问题中发挥核心作用的国家。从历史上看，阿拉斯加 当地人(AN)能够从传统食物中摄取足够的维生素D，最明显的是来自三文鱼， 尽管生活在纬度地区，一年中的大部分时间都会阻止皮肤中维生素D的合成。 乡村雪橇狗也是如此。随着对传统食物的转变，环极地的人们 北方的维生素D缺乏症患病率正在上升。是的，孩子们正在患软骨病。 更高的发病率，而老年人一直表现出更高的血清维生素D水平；这与全国范围内的情况形成鲜明对比 趋势。据估计，全世界有超过10亿人缺乏维生素D。 与多种疾病有关，包括新陈代谢障碍、衰老和认知障碍。 尽管如此，对于达到人体和人体足够水平的推荐摄入量，几乎没有达成共识。 狗的情况就更糟了。因此，迫切需要更好地了解维生素D的摄入量。 在北极圈，那里有最高的缺乏风险，以了解饮食、年龄、 维生素D状态和新陈代谢健康。这项研究将开始填补有关维生素的知识空白。 D缺乏症的具体目的如下：1)大脑老化的标志与维生素D状态有关 北极圈的动物模型和2)确定从野生的维生素D增加的影响 阿拉斯加鲑鱼对胰岛素信号和代谢健康生物标志物的影响。体积和形态 老年人和年轻人的大脑灰质和白质的变化将通过磁共振成像进行评估 并与血清维生素D水平相关。除了代谢综合征的其他标志物外， 外周血单个核细胞上的胰岛素反应性葡萄糖转运体(GLUT4)将在 不同年龄雪橇犬补充野生阿拉斯加前后对胰岛素的反应 三文鱼。这一项目的预期结果将有助于维生素D相关数据的不足 仅依靠膳食摄入量获得足够食物的人群的需求、状况和健康结果。