Benefits of conjugated linoleic acid on aging

描述(申请人提供)：最近由于卡路里摄入量增加和体力活动减少而导致的肥胖率上升与年龄相关疾病的更高发病率有关，例如心血管疾病、2型糖尿病和某些恶性肿瘤，这些疾病被认为是导致老年人功能下降和生活质量下降的原因。随着年龄的增长，肥胖会增加脂肪质量，减少瘦体重，这会导致老年人的骨质流失和随后的骨折。事实上，肌肉无力是导致虚弱的主要因素；导致残疾、急性疾病、疼痛和过早死亡。近年来，共轭亚油酸(CLA)作为一种可能的减肥膳食补充剂受到了越来越多的关注。在几种动物模型中，共轭亚油酸被发现可以减少脂肪质量和增加瘦体重。在一些人体研究中也得到了类似的结果。我们推测，特别是在中年或晚年补充低饮食的CLA可以预防骨质疏松症和骨质疏松症，从而减少跌倒和骨折，并防止老年人的发病率和死亡率。为了建立这一临床相关假说，我们建议进行以下研究。具体目的1.测定6-12、12-18和18-24个月龄C57BL/6小鼠(轻度易患2型糖尿病和骨质疏松症)在添加或不添加CLA(0.5%)的情况下脂肪和瘦体质量的增龄性变化，并与血糖、胰岛素、瘦素水平以及肿瘤坏死因子-α和IL-6细胞因子水平的变化进行相关性研究。具体目的2.测定补充和不补充共轭亚油酸对小鼠骨髓细胞中破骨细胞和破骨细胞特异性转录因子的激活和骨密度的影响。基于我们在年轻小鼠中的初步数据，如果我们在老年小鼠中进行的拟议研究发现共轭亚油酸对年龄相关的骨骼减少和骨密度丢失有好处，结果将非常有助于测试在婴儿潮一代人群中使用共轭亚油酸作为饮食补充剂的可行性。

DESCRIPTION (provided by applicant): Recent rise in obesity due to increased calorie intake and decreased physical activity is linked to the higher incidence of age-related diseases e.g. cardiovascular, type 2 diabetes and certain malignancies which are known to contribute to functional decline and impaired quality of life in older population. With age, obesity increases fat mass and decreases lean body mass which is found to cause bone loss and subsequent fractures in the elderly. In fact, muscle weakness is the major contributing factor in causing frailty; resulting in disability, acute illness, pain and early deaths. In recent years, there has been a growing interest in conjugated linoleic acid (CLA) as a possible dietary supplement to reduce obesity. CLA is found to decrease fat mass and increase lean body mass in several animal models. Similar results have also been obtained in some human studies. We hypothesize that supplementing low dietary CLA particularly during midlife or late age will prevent sarcopenia and osteoporosis, thereby decreasing falls and fractures, and preventing both morbidity and mortality in the elderly. To establish this clinically related hypothesis we propose to undertake the following studies. Specific aim 1. To measure age-related changes in fat and lean body mass in 6-12, 12-18 and 18-24 months old C57BL/6 mice (mildly prone to develop type 2 diabetes and osteoporosis), with or without CLA (0.5%), and correlate with plasma glucose, insulin, leptin levels and changes in TNF-alpha and IL-6 cytokine levels. Specific Aim 2. To measure age-related changes in BMD, activation of osteoclasts and osteoclast specific transcription factors in bone marrow cells of mice, with and without CLA supplementation. Based on our preliminary data in young mice, if our proposed studies in older mice find beneficial effect of CLA against age related sarcopenia and BMD loss, the results would be very useful to test the feasibility of using CLA as a dietary supplement in the baby boomer population.