Energetics, Disparities, & Lifespan: A unified hypothesis

描述（由申请人提供）：在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有着错综复杂的关系，但这些相互关系的性质却知之甚少。事实上，像为什么我们会变老这样的根本问题仍然没有答案，而一些次要的问题，比如为什么热量限制会导致寿命延长，为什么在发达国家，较低的社会经济地位与肥胖有关，也仍然没有答案。在这里，我们提出了一个统一的模型，由进化思维的生活策略，连接这些现象。在这个模型中，衰老或更准确地说衰老不是由于环境的损害或代谢燃料而被动地发生在我们身上的事情，而是我们做的事情。也就是说，死亡率或衰老率被视为（部分）内部可调节的现象，就像恒温动物对体温的控制一样，其中调节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。我们在此阐述这一理论，并从中得出七个具体的假设，其中每一个都是在不同的实验中使用模式生物进行检验。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，以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.