Evolutionary Considerations on Aging and Alzheimer's Disease

A. Gunten, Marie-Thérèse Clerc, R. Tomar, P. John-Smith
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引用次数: 3

Abstract

Increasingly people are surviving into old age both in high and middle/low income countries. The increase in longevity is associated with increased levels of morbidity of both somatic and mental disorders during those added years. These pathologies prompt developing strategies for effective prediction, prevention and treatment of such disorders, among them the dementias such as Alzheimer’s disease (AD). Aging lies on a temporal continuum that starts at conception and ends at death. It refers to the aging processes occurring during an individual’s lifetime. However, our understanding of aging remains limited. In the early stages of dementia, distinguishing normal from pathological aging remains complex. Medical research customarily investigates the immediate mechanisms or pathogenesis of “how” diseases come about and affect patients. Evolutionary perspectives consider the reasons “why” people may have become particularly vulnerable to different conditions. Examining why people age is illuminating. Around the question whether aging is adaptive, we consider some evolutionary concepts useful around aging theories, among others antagonistic pleiotropy and life history theory and more recent concepts including evolvability and evolutionary developmental biology. As AD seems to be specific to homo sapiens, its existence may in part be anchored in the adaptive changes that have occurred after the hominidae separated from the pongidae. Around the question why apparently non-adaptive conditions such as AD are so frequent, we consider, among other aspects, brain development including the related phenomena of altriciality and grandmothering, the evolution of ApoE and the genome lag hypothesis. We consider the idea that the neuropathological hallmarks of AD help mitigate neurodegeneration and cognitive decline rather than being its cause. Thus, an evolutionary look into AD may shed new light on the currently still sombre perspectives regarding disease-modifying treatments of AD and prove useful as a root cause analysis.
衰老和阿尔茨海默病的进化考虑
在高收入国家和中/低收入国家,越来越多的人活到老年。寿命的延长与身体和精神疾病发病率的增加有关。这些病理促使制定有效预测、预防和治疗这些疾病的策略,其中包括阿尔茨海默病(AD)等痴呆症。衰老是一个时间连续体,从受孕开始,到死亡结束。它指的是一个人一生中发生的衰老过程。然而,我们对衰老的理解仍然有限。在痴呆症的早期阶段,区分正常衰老和病理性衰老仍然很复杂。医学研究通常是调查疾病发生和影响病人的直接机制或发病机制。进化论的观点考虑了人们在不同条件下变得特别脆弱的原因。研究人们变老的原因很有启发性。围绕衰老是否具有适应性的问题,我们考虑了一些与衰老理论有关的有用的进化概念,其中包括拮抗多效性和生活史理论,以及最近的概念,包括可进化性和进化发育生物学。由于阿尔茨海默氏症似乎是智人特有的,它的存在可能部分归因于人科从猿类分离出来后发生的适应性变化。围绕为什么像AD这样明显的非适应性疾病如此频繁的问题,我们考虑了大脑发育的其他方面,包括肥胖和祖母化的相关现象,ApoE的进化和基因组滞后假说。我们认为阿尔茨海默病的神经病理学特征有助于减轻神经变性和认知能力下降,而不是其原因。因此,对阿尔茨海默病的进化研究可能会为目前关于阿尔茨海默病的疾病改善治疗的悲观观点提供新的视角,并被证明是有效的根本原因分析。
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