Adaptive Responses to Stress and Mortality Risk with Emphasis on Aging Rates

我的实验室试图了解为什么动物的衰老速度如此不同，哪些过程与衰老有关，以及我们如何操纵衰老速度。研究衰老需要寿命短的动物。我们把蟋蟀作为衰老的模型，因为年轻的蟋蟀长得像成年人，吃的食物也相似。影响蟋蟀衰老的基因在所有动物中都非常相似。蟋蟀的寿命约为120天，而迄今为止最长寿的人类寿命为122岁。我们已经将板球的寿命延长到257天。我们设计了一种多成分的饮食配方，可以延长寿命，减少癌症，并减缓衰老小鼠大脑和身体的恶化。这种疗法旨在帮助与衰老相关的五种疾病。这些措施包括1)中和在所有动物细胞中产生能量的微小熔炉(称为线粒体)产生的有毒副产品。这些副产品本质上会导致“生物生锈”；2)使炉子工作得更好，这样它们产生的毒素更少，但仍然产生足够的能量，以防止否则伴随衰老而出现的衰退；3)减少可能导致损害的免疫系统的过度活动；4)维持胰岛素的活动(与能量供应和糖尿病有关)；以及5)维持年轻的细胞膜，该细胞膜传递神经元放电，并在所有动物细胞中运输食物、O2、CO2和废物。板球研究将帮助我们获得一种改进的干预措施，作为一种研究工具。有两件事对衰老有很大影响，那就是生长和抗压能力。此外，这些功能是相互对抗的。快速生长降低了抗逆性和寿命，而诱导抗逆性往往会减缓生长并延长寿命。长寿动物通常生长较慢(例如，生长缓慢的大象和乌龟与生长迅速的老鼠和兔子相比)。我们将研究营养、植物化学物质、环境毒素和辐射如何影响蟋蟀的生长、抗逆性和衰老。除了测量身体活动和记忆力等特征外(蟋蟀学到了！)我们将测量身体随年龄的变化(例如，荷尔蒙、能量供应和损伤)与抗应激和健康相关。我们还发现，早睡过程促进生长(和衰老)，而抗压能力(和生命维持)在晚睡得到控制。事实上，不相容的功能，如生长和抗逆性，在不同的时间主要处于活跃状态，这意味着生物时钟与衰老高度相关。因此，延缓衰老的干预措施可能需要考虑到时钟才是最有效的。我们的研究具有潜在的广泛应用，因为所有较高级的动物年龄(例如，野生动物、牲畜、动物园居民、宠物、水产养殖)。因为生长、抗压性和衰老是相互关联的，所以研究结果也对管理辐射、污染、植物毒素和极端环境等应激源的暴露有影响。**

My laboratory seeks to understand why animals age at such different rates, what processes are associated with aging and how we can manipulate aging rates. Studying aging requires animals that have short lives. We developed crickets as a model of aging because young crickets resemble adults and eat similar food. Genes that impact aging in crickets are VERY similar in all animals. Crickets live about 120 days whereas the oldest human so far lived 122 years. We have extended the cricket lifespan to 257 days. We designed a multi-ingredient dietary formulation that extends longevity, reduces cancer and slows deterioration in the brains and bodies of aging mice. This treatment was designed to help five things associated with aging. These include 1) neutralizing the toxic byproducts generated by the tiny furnaces (called mitochondria) that make energy in all animal cells. These byproducts essentially cause "biological rusting;" 2) making the furnaces work better so they produce less toxins but still make enough energy to prevent the declines otherwise accompanying aging; 3) reducing excess activity of the immune system that can cause damage; 4) maintaining the actions of insulin (related to energy supply and diabetes); and 5) maintaining youthful cell membranes that transmit neuronal firing and transport food, O2, CO2 and waste in all animal cells. Cricket studies will help us derive an improved intervention that can serve as a research tool. Two things that strongly vary aging are growth and stress resistance. Moreover, these functions are antagonistic. Rapid growth reduces both stress resistance and life span whereas induction of stress resistance tends to slow growth and extend longevity. Long lived animals generally grow slower (e.g., slow-growing elephants and turtles versus fast growing mice and rabbits). We will examine how nutrition, plant chemicals, environmental toxins and radiation affect growth, stress resistance and aging in crickets. Besides measuring features like physical activity and memory (crickets learn!) we will measure changes in the body with age (e.g., hormones, energy supply, and damage) associated with stress resistance and health. We also found that processes that occur in early sleep promote growth (and aging) whereas stress resistance (and life support) are managed in late sleep. The fact that incompatible functions like growth and stress resistance are mainly active at different times means that the biological clock is highly relevant to aging. Thus, interventions to slow aging likely need to take the clock into account to be most effective. Our studies have potentially broad applications since all higher animals age (e.g., wildlife, livestock, zoo residents, pets, aquaculture). Because growth, stress resistance and aging are linked, results also have implications for managing exposure to stressors like radiation, pollution, plant toxins, and environmental extremes.**