Developing and testing the evolutionary reliability theory of senescence

衰老，以及随之而来的身体退化，是人类经历的一个普遍部分，似乎是不可避免的。然而，为什么我们的身体会恶化，为什么我们的死亡风险会随着年龄的增长而增加？为什么衰老是生命之树中普遍存在的现象，从细菌到最复杂的多细胞生物？而且，最相关的是，既然衰老对生物体的生存和繁殖能力有害，为什么自然选择没有将它从种群中清除出去，以至于死亡的唯一原因是“外在的”原因，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，并形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年龄特异性有害影响的基因上。然而，由于专注于具有负面影响的功能基因，这些理论忽视了老年学家所认为的衰老的主要近因：自由基和紫外线辐射等危害造成的损伤积累。因此，我建议开发和测试一个新兴的新理论，以损害为中心的方法来老化的演变。我的学生和我将结合联合收割机可靠性理论（一个分支的应用概率，处理损害，生存和寿命）与进化动力学（一个正式的数学方法来进化），以产生数学和计算机模型，以帮助推进“进化可靠性老化理论”。这些模型将产生假设，我们将使用在不同环境条件下进化的物种的广泛比较，并使用一套旨在检查昆虫衰老的对照实验来进行测试。这项工作将帮助我们理解老龄化的奥秘，这是一个具有根本学术意义的问题，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急剧变化过程中的国家。

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.