Benefits of conjugated linoleic acid on aging

描述（由申请方提供）：由于热量摄入增加和体力活动减少导致的肥胖症近期增加与年龄相关疾病（如心血管、2型糖尿病和某些恶性肿瘤）的发病率较高有关，已知这些疾病会导致老年人群的功能下降和生活质量受损。随着年龄的增长，肥胖会增加脂肪量并减少瘦体重，这被发现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，人们越来越关注共轭亚油酸（CLA）作为一种可能的膳食补充剂，以减少肥胖。在几种动物模型中发现CLA可以减少脂肪量并增加瘦体重。在一些人体研究中也获得了类似的结果。我们假设，特别是在中年或晚年，补充低膳食CLA将预防肌肉减少症和骨质疏松症，从而减少福尔斯和骨折，并防止老年人的发病率和死亡率。为了建立这一临床相关的假设，我们建议进行以下研究。具体目标1.测量6-12、12-18和18-24月龄C57 BL/6小鼠（轻度倾向于发展2型糖尿病和骨质疏松症）中脂肪和瘦体重的年龄相关变化，有或没有CLA（0.5%），并与血糖、胰岛素、瘦素水平以及TNF-α和IL-6细胞因子水平的变化相关。具体目标2。测量有和没有CLA补充的小鼠的BMD、破骨细胞和破骨细胞特异性转录因子的活化的年龄相关变化。根据我们在年轻小鼠中的初步数据，如果我们在老年小鼠中的研究发现CLA对年龄相关的肌肉减少症和BMD损失的有益作用，那么结果将非常有用，以测试使用CLA作为婴儿潮人群膳食补充剂的可行性。

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.