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

项目摘要 我们的长期目标是确定人类和犬类的维生素D摄入水平和维生素D充足率 生活在北极圈我们的总体目标是（i）确定实际年龄如何影响维生素D 状态和形态学变化的雪橇狗模型，和（ii）确定鲑鱼对维生素D的影响 老年和青年雪橇犬代谢综合征和胰岛素信号的状态和标志物。与他们的短 狗的寿命和平行的生化途径，狗已成为一个重要的生物医学研究模型， 痴呆相关的损伤和胰岛素信号。特别是雪橇犬， 环北极地区的健康模式，因为他们是传统的生存生活方式的一部分。来 在过去的100年里，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。这一营养转型 被认为在远北地区人民当前的公共卫生问题中发挥着核心作用。历史上，阿拉斯加 原住民（AN）能够从传统食物中摄取足够的维生素D，特别是鲑鱼， 尽管生活在高纬度地区，一年中的大部分时间里，阳光都阻止皮肤合成维生素D。 对于乡村雪橇犬来说也是如此。随着人们对传统食物的抛弃， 北方正在经历维生素D缺乏症的流行率增加。Yup'ik的孩子们正在患上佝偻病， 较高的发病率，而老年人始终表现出较高的血清维生素D水平;这与国家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。维生素D缺乏症 与多种疾病有关，包括代谢紊乱、衰老和认知障碍。 尽管如此，在推荐摄入量方面几乎没有达成共识，以达到人类的足够水平， 对狗来说更是如此。因此，迫切需要更好地了解维生素D的摄入量， 北极圈，那里是缺乏的风险最高的地方，了解饮食，年龄， 维生素D状况和代谢健康。这项研究将开始填补有关维生素的知识空白 维生素D缺乏症有以下具体目标：1）将脑老化的标志物与维生素D状态相关联， 北极圈的动物模型和2）确定从野生动物中增加维生素D的影响 阿拉斯加鲑鱼对胰岛素信号和代谢健康的生物标志物。体积和形态 将通过磁共振成像评估老年人和年轻人脑灰质和白色物质的变化 狗和相关的血清维生素D状态。除了代谢综合征的其他标志物外， 外周血单核细胞上的胰岛素响应性葡萄糖转运蛋白（GLUT 4）将在 不同年龄雪橇犬在补充野生阿拉斯加雪橇犬之前和之后对胰岛素的反应 三文鱼该项目的预期成果将有助于补充有关维生素D的数据不足 需求，状态和健康结果的人口，完全依赖于膳食摄入量，以获得足够的。

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.