Energetics, Disparities, & Lifespan: A unified hypothesis

能量、差异、

• 批准号: 8412364
• 负责人: DAVID B ALLISON
• 金额: $ 198.52万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8412364
• 关键词: Affect; African American; Age; Aging; Aging-Related Process; Animal Feed; Animal Model; Animals; Appetite Depressants; Biological Clocks; Body Temperature; Body Weight decreased; Body fat; Breeding; Buffers; Caloric Restriction; Chronic; Control Animal; Data; Developed Countries; Disadvantaged; Eating; Economics; Energy Intake; Environment; Evolution; Fatty acid glycerol esters; Feeling; Food; Food Energy; Genetic; Growth; Health; Hispanic Americans; Hispanics; Human; Hunger; Individual; Investigation; Knowledge; Lead; Life; Link; Logic; Longevity; Maintenance; Metabolism; Methods; Modeling; Nature; Obesity; Older Population; Organism; Outcome; Output; Pathway interactions; Perception; Persons; Physiological; Policies; Population; Positioning Attribute; Predatory Behavior; Process; Public Health; Quality of life; Randomized; Reaction; Regulation; Relative (related person); Reproduction; Research; Research Personnel; Rosa; Schedule; Security; Self Perception; Social status; Socioeconomic Status; Specific qualifier value; Stimulus; System; Taxation; Temperature; Testing; Thinking; Time; Uncertainty; Work; classical conditioning; exhaust; experience; fitness; follow-up; health disparity; healthy aging; improved; low socioeconomic status; mimetics; mortality; neuronal cell body; novel; reproductive; research study; response; senescence; social; socioeconomics; theories

DESCRIPTION (provided by applicant): The evolution and ontogeny of lifespan at the species and individual level, the energetics of the organism in its environment, the storage of metabolizable energy as body fat, and socioeconomic disparities within populations all seem intricately related and yet the nature of these interrelations is poorly understood. Indeed questions as fundamental as why we age remain open and subsidiary questions such as why caloric restriction leads to increased lifespan and why lower socioeconomic status is related to obesity in developed countries also remain unanswered. Herein, we propose a unified model informed by evolutionary thinking about life strategies which connects these phenomena. In this model, aging or more precisely senescence is not something that passively happens to us as the result of environmental insults or from metabolizing fuel, but is something we do. That is, mortality rate or the rate of aging is seen as (partially) internally regulable phenomenon much like the control of body temperature in homeotherms in which the regulated rate is responsive to perceptions about the energetic state of the environment. From this perspective, it is perceptions of the energetic security of the environment that are a key factor in linking these phenomena. We elaborate this theory herein and from it derive seven specific hypotheses, each of which is testable in a different experiment using model organisms. We have assembled a team of the world's leading researchers to conduct these seven experiments and then to conduct follow-up work to study both a priori specified potential causal mechanisms involving internal clock regulation and also to conduct exploratory work to identify new potential mechanisms. Outcomes from this work will have profound implications for our understanding of the nature of aging, of health disparities, and of obesity. PUBLIC HEALTH RELEVANCE: Maximizing quality of life for citizens from all social strata and at all ages requires an understanding of the factors that lead to disparities in health, to differences in body fat levels, and to healthier aging in our increasingly older population. The proposed research will contribute such knowledge.

描述(申请人提供)：物种和个体层面上寿命的进化和个体发育，有机体在其环境中的能量学，作为体脂的代谢能量的储存，以及种群内的社会经济差异，这些似乎都是错综复杂的关系，但这些相互关系的性质却鲜为人知。事实上，像我们为什么变老这样的根本问题仍然悬而未决，而诸如为什么限制卡路里摄入会延长寿命，以及为什么发达国家较低的社会经济地位与肥胖有关等附属问题也仍然没有得到回答。在这里，我们提出了一个统一的模型，该模型受到生命策略进化思维的启发，将这些现象联系在一起。在这个模型中，衰老，或者更准确地说，衰老不是由于环境侮辱或燃料代谢而被动发生在我们身上的事情，而是我们所做的事情。也就是说，死亡率或衰老速度被视为(部分)内部可调节的现象，很像恒温动物对体温的控制，在恒温动物中，调节的速率对环境能量状态的感知做出反应。从这个角度来看，对环境的能量安全的看法是将这些现象联系起来的一个关键因素。我们在这里详细阐述了这一理论，并由此得出了七个具体的假设，每个假设都可以在使用模型生物的不同实验中得到验证。我们召集了一个由世界领先的研究人员组成的团队来进行这七个实验，然后进行后续工作，研究涉及内部时钟调节的先验指定的潜在因果机制，并进行探索性工作，以确定新的潜在机制。这项工作的结果将对我们理解老龄化、健康差距和肥胖的本质产生深远的影响。 公共卫生相关性：要最大限度地提高所有社会阶层和各个年龄段公民的生活质量，需要了解导致健康差异、体脂水平差异以及我们日益老龄化的人口更健康老龄化的因素。拟议的研究将有助于提供此类知识。