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

对压力和死亡风险的适应性反应，重点关注老龄化率

• 批准号: RGPIN-2015-05693
• 负责人: Rollo, Christopher
• 金额: $ 1.75万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613694
• 关键词: Adaptive; Responses; Stress; Mortality; Risk

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.

我的实验室试图理解为什么动物的衰老速度如此不同，与衰老相关的过程是什么，以及我们如何操纵衰老速度。研究衰老需要寿命较短的动物。我们把蟋蟀作为衰老的模型，因为小蟋蟀和成年蟋蟀很像，吃的食物也很相似。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年。我们把蟋蟀的寿命延长到了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，减缓衰老小鼠大脑和身体的恶化。这种治疗旨在帮助与衰老有关的五个方面。这包括1)中和所有动物细胞中产生能量的微小熔炉（称为线粒体）产生的有毒副产物。这些副产品基本上会导致“生物生锈”；2)使熔炉更好地工作，使它们产生更少的毒素，但仍能产生足够的能量，以防止因老化而导致的衰退；3)减少可能造成损害的免疫系统的过度活动；4)维持胰岛素的作用（与能量供应和糖尿病有关）；5)维持年轻的细胞膜，在所有动物细胞中传递神经元放电和运输食物、氧气、二氧化碳和废物。对蟋蟀的研究将帮助我们得出一种改进的干预方法，可以作为一种研究工具。有两件事强烈地改变了衰老：生长和抗逆性。此外，这些功能是拮抗的。快速生长会降低抗逆性和寿命，而诱导抗逆性则会减缓生长并延长寿命。长寿的动物通常长得较慢（例如，长得慢的大象和乌龟与长得快的老鼠和兔子）。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（蟋蟀会学习！）等特征外，我们还将测量身体随年龄的变化（例如，激素、能量供应和损伤），这些变化与抗压力和健康有关。我们还发现，在早期睡眠中发生的过程促进了生长（和衰老），而抗压力（和生命支持）在后期睡眠中得到管理。事实上，生长和抗逆性等不相容的功能主要在不同的时间活跃，这意味着生物钟与衰老高度相关。因此，减缓衰老的干预措施可能需要将生物钟考虑在内才能最有效。我们的研究具有潜在的广泛应用，因为所有的高等动物年龄（例如，野生动物，牲畜，动物园居民，宠物，水产养殖）。由于生长、抗逆性和衰老是相互关联的，研究结果也对管理辐射、污染、植物毒素和极端环境等压力源的暴露有影响。