Energetics, Disparities, & Lifespan: A unified hypothesis

描述（由申请人提供）：物种和个体水平上的生命进化和个体发生，生物体在其环境中的能量学，代谢能作为体脂的储存，以及种群内的社会经济差异，似乎都是错综复杂的相关，但这些相互关系的本质却知之甚少。事实上，像为什么我们会变老这样的基本问题仍然没有定论，而诸如为什么热量限制会延长寿命、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没有答案。在此，我们提出了一个统一的模型，该模型由有关生命策略的进化思想提供信息，将这些现象联系起来。在这个模型中，衰老或更准确地说，衰老不是由于环境损害或代谢燃料而被动发生在我们身上的事情，而是我们自己做的事情。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，就像恒温动物对体温的控制一样，在恒温动物中，被调节的速度是对环境能量状态的感知做出反应的。从这个角度来看，对环境的能源安全的认识是把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，并从中得出了七个具体的假设，每个假设都可以在使用模式生物的不同实验中进行测试。我们已经组建了一个由世界领先的研究人员组成的团队来进行这七项实验，然后进行后续工作，既研究先天指定的涉及内部时钟调节的潜在因果机制，也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衰老、健康差异和肥胖的本质产生深远的影响。

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.