Developing and testing the evolutionary reliability theory of senescence

衰老，以及随之而来的身体退化，是人类经历中如此普遍的一部分，似乎是不可避免的。然而，为什么我们的身体要退化，为什么我们的死亡风险会随着年龄的增长而增加？从细菌到最复杂的多细胞生物体，为什么衰老是生命之树中普遍存在的现象？而且，最恰当的是，鉴于衰老对生物体的生存和繁殖能力是有害的，为什么自然选择没有将其从种群中清除出去，这样唯一的死亡原因就是外在的，比如捕食和传染病？这些关于衰老进化的问题长期以来一直困扰着生物学家，并构成了这项研究计划的支柱。直到最近，大多数关于衰老进化的主流理论都集中在具有特定年龄有害影响的基因上。然而，由于专注于具有负面影响的功能基因，这些理论忽略了老年学家认为的导致衰老的主要直接原因：自由基和紫外线辐射等危险因素造成的损害的积累。因此，我建议开发和测试一种新兴的新理论，以损伤为中心的方法来研究衰老的进化。我和我的学生们将把可靠性理论(应用概率的一个分支，涉及损伤、存活和寿命)与进化动力学(进化的一种正式数学方法)结合起来，产生数学和计算机模型，以帮助推进“衰老的进化可靠性理论”。这些模型将产生假说，我们将通过对在不同环境条件下进化的物种进行广泛比较，并使用一系列旨在检查昆虫衰老的对照实验来检验这些假说。这项工作将帮助我们理解老龄化之谜，这是一个具有基本学术意义的问题，也具有重要的医学和经济意义，特别是在加拿大这样一个目前正处于人口结构戏剧性变化过程中的国家。

Aging, and the bodily deterioration that comes with it, is such a universal part of human experience that it seems inevitable. Yet, why should our bodies deteriorate, and why does our risk of death increase, as we get older? Why is aging a ubiquitous phenomenon in the tree of life, from the bacteria to the most complex multicellular organisms? And, most pertinently, given that aging is detrimental to organisms' ability to survive and reproduce, why hasn't natural selection purged it from populations, so that the only causes of death are 'extrinsic' ones, such as predation and infectious disease? These questions regarding the evolution of aging have long vexed biologists, and form the backbone of this research program. Until recently, most mainstream theories of the evolution of aging centered on genes with age-specific detrimental effects. Yet, by concentrating on functioning genes with negative effects, such theories neglect what gerontologists see as the main proximate cause of aging: the accumulation of damage due to hazards like free-radicals and UV radiation. Thus, I propose to develop and test an emerging new theory that takes a damage-centric approach to the evolution of aging. My students and I will combine Reliability Theory (a branch of applied probability that deals with damage, survival, and longevity) with Evolutionary Dynamics (a formal mathematical approach to evolution) to produce mathematical and computer models to help advance an 'Evolutionary Reliability Theory of Aging'. These models will generate hypotheses which we will put to the test using broad comparisons of species that evolved under different environmental conditions, and using a suite of controlled experiments designed to examine aging in insects. This work will help us understand the enigma of aging, a question of fundamental academic importance which also has important medical and economic implications, especially in a country such as Canada that is currently in the process of a dramatic demographic shift.