[论文解读] Traditional aging theories: which ones are useful?

Jicun Wang-Michelitsch, Thomas M. Michelitsch|arXiv (Cornell University)|Mar 24, 2015

Genetics, Aging, and Longevity in Model Organisms参考文献 53被引用 6

一句话总结

本文批判性地评估了传统的衰老理论，认为大多数理论因忽视了损伤累积和发育过程而存在不完整性。它指出发育理论和损伤（故障）累积理论最为有用，同时强调熵增和复杂性丧失等物理原理在衰老中具有广泛适用性，呼吁建立一个整合这些洞见的统一理论。

ABSTRACT

Many theories have been proposed to answer two questions on aging: "Why do we age?" and "How do we age?" Among them, evolutionary theories are proposed to interpret the evolutionary advantage of aging, and "saving resources for group benefit" is thought to be the purpose of aging. However for saving resources, a more economic strategy should be to make a rapid death to the individuals who are over the reproduction age rather than to make them aging. Biological theories are proposed to identify the causes and the biological processes of aging. However, some theories including cell senescence/telomere theory, gene-controlling theory, and developmental theory, have unfortunately ignored the influence of damage on aging. Free-radical theory suggests that free radicals by causing intrinsic damage are the main cause of aging. However, even if intracellular free radicals cause injuries, they could be only associated with some but not all of the aging changes. Damage (fault)-accumulation theory predicts that faults as intrinsic damage can accumulate and lead to aging. However, in fact an unrepaired fault could not possibly remain in a living organism, since it can destroy the integrity of tissue structure and cause rapid failure of the organism. These traditional theories are all incomplete on interpreting aging phenomena. Nevertheless, developmental theory and damage (fault)-accumulation theory are more useful, because they have recognized the importance of damage and development process in aging. Some physical theories are useful, because they point out the common characteristics of aging changes, including loss of complexity, consequence of increase of entropy, and failure of information-transmission. An advanced theory, which can include all of these useful ideas in traditional theories, is needed.

研究动机与目标

• 评估既有的衰老理论在解释衰老机制和进化基础方面的有用性。
• 识别主流理论（如自由基理论、端粒理论和基因调控理论）的局限性。
• 主张损伤累积和发育过程是理解衰老的核心。
• 强调熵增和复杂性丧失等物理原理在衰老现象中具有普遍相关性。
• 倡导建立一个整合现有模型中最优要素的新统一理论。

提出的方法

• 系统性回顾和批判性分析主要传统衰老理论，包括进化、生物学和物理理论。
• 基于生物学合理性和实证支持，评估每种理论解释“为何我们衰老”和“我们如何衰老”的能力。
• 评估内在损伤（故障）在衰老中的作用，强调未修复的故障无法持续存在，否则将导致生物体功能衰竭。
• 运用熵、复杂性丧失和信息传递失效等物理原理作为贯穿衰老现象的跨领域框架。
• 基于理论对发育过程和损伤累积的承认程度，对不同理论进行比较。
• 将现有理论中最优的组成部分整合，形成新综合性衰老理论的概念基础。

实验结果

研究问题

• RQ1 哪些传统衰老理论能为理解衰老过程提供科学上有用的框架？
• RQ2 为何进化衰老理论无法将衰老解释为一种节约资源的机制？
• RQ3 为何关键生物学理论中忽视损伤累积会限制其解释力？
• RQ4 熵增和复杂性丧失等物理原理在多大程度上普遍适用于各类生物系统中的衰老现象？
• RQ5 应从现有理论中整合哪些核心要素，以构建一个更全面的衰老新理论？

主要发现

• 自由基理论不足，因为自由基仅能解释部分衰老变化，而非全部。
• 细胞衰老和端粒理论忽视了内在损伤累积在衰老中的关键作用。
• 基因调控理论和发育理论因未能充分解释与损伤相关的机制而存在局限。
• 损伤（故障）累积理论具有实用性，因为它认识到故障无法在不引发生物体功能衰竭的情况下长期存在。
• 发育理论具有价值，因为它纳入了发育过程在衰老中的作用。
• 强调熵增、复杂性丧失和信息传递失效的物理理论，为衰老现象提供了广泛而普遍的洞察。