"Exercise Mediated Systemic Cellular Protection - ""Exerkines"""

众所周知，定期耐力运动对运动骨骼肌以外的组织和器官具有保护作用，并可能延缓衰老的影响。一些证据表明，肌肉释放内分泌因子(荷尔蒙)进入血液循环，通过血液流向远处的组织，并激活细胞过程，为这些组织提供保护。常见的例子包括经常锻炼可以降低患某些癌症的风险，以及锻炼可以增加大脑中神经的形成。我们已经证明，在经过基因改造以适应年龄增长的小鼠中，锻炼(每周三次，持续五个月)可以迅速为各种器官和组织(眼睛、性腺、骨髓、皮肤)提供保护，并防止线粒体损伤(线粒体是细胞的动力库)。然后，我们从锻炼的人身上提取血清，发现这些血清激活了培养中的细胞(培养皿)，并对线粒体有很强的有益影响。后一项观察从背景到目前的建议，我们将进一步探索运动相关系统因子(“运动素”)的概念，以确定它们的身份，特别是它们如何作用于未运动的组织，以增强细胞活力和线粒体能力。这项研究将涉及使用尖端技术，包括蛋白质组学(一次识别许多蛋白质)和基因组学(确定基因表达“特征”)，以表征运动后发生变化的蛋白质，以及它们如何改变活体组织(肌肉、神经、结缔组织和上皮)中的细胞通路。从这些实验中获得的数据可能会识别出最终可以用于治疗与衰老相关的常见疾病(肌肉萎缩/骨质疏松症、阿尔茨海默病、癌症等)的蛋白质。

It is well known that regular endurance exercise provides protective benefit to tissues and organs outside of the exercising skeletal muscle and may delay the effects of aging. Several lines of evidence suggest that muscle releases endocrine factors (hormones) into the circulation that travel by the blood stream to distant tissues and activate cellular process that confer protection on those tissues. Common examples would include the lower risk of certain cancers with regular exercise and the fact that exercise can increase nerve formation in the brain. We have shown that exercise (three times per week for five months) in mice that were genetically altered to age rapidly provided protection to a variety of organs and tissues (eyes, gonads, bone marrow, skin) and prevented mitochondrial damage (the mitochondria is the powerhouse of the cell). We then took serum from exercising humans and found that the serum activated cells in culture (Petri dish) and had a strong beneficial influence on the mitochondria. The latter observations from the background to the current proposal where we will further explore the concept of exercise related systemic factors ("exerkines") to determine their identity and specifically how they act on non-exercised tissue to enhance cell vitality and mitochondrial capacity. The study will involve the use of cutting edge technology including proteomics (identifying many proteins at once) and genomics (identifying the gene expression "signature") to characterize the proteins that change following exercise and how they alter cellular pathways in every tissue in living organisms (muscle, nerve, connective and epithelial). The data obtained from these experiments may identify proteins that can be eventually used as a therapy for patients with diseases that are common with aging (muscle atrophy/sarcopenia, Alzheimer's disease, cancer, etc.).