An evolutionary medicine and life history perspective on aging and disease: Trade-offs, hyperfunction, and mismatch.

IF 3.3 3区 医学 Q2 EVOLUTIONARY BIOLOGY
Evolution, Medicine, and Public Health Pub Date : 2025-05-15 eCollection Date: 2025-01-01 DOI:10.1093/emph/eoaf010
Jacob E Aronoff, Benjamin C Trumble
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引用次数: 0

Abstract

The rise in chronic diseases over the last century presents a significant health and economic burden globally. Here, we apply evolutionary medicine and life history theory to better understand their development. We highlight an imbalanced metabolic axis of growth and proliferation (anabolic) versus maintenance and dormancy (catabolic), focusing on major mechanisms including IGF-1, mTOR, AMPK, and Klotho. We also relate this axis to the hyperfunction theory of aging, which similarly implicates anabolic mechanisms such as mTOR in aging and disease. Next, we highlight the Brain-Body Energy Conservation model, which connects the hyperfunction theory with energetic trade-offs that induce hypofunction and catabolic health risks such as impaired immunity. Finally, we discuss how modern environmental mismatches exacerbate this process. Following our review, we discuss future research directions to better understand health risk. This includes studying IGF-1, mTOR, AMPK, and Klotho and how they relate to health and aging in human subsistence populations, including with lifestyle shifts. It also includes understanding their role in the developmental origins of health and disease as well as the social determinants of health disparities. Furthermore, we discuss the need for future studies on exceptionally long-lived species to understand potentially underappreciated trade-offs and costs that come with their longevity. We close with considering possible implications for therapeutics, including (i) compensatory pathways counteracting treatments, (ii) a "Goldilocks zone," in which suppressing anabolic metabolism too far introduces catabolic health risks, and (iii) species constraints, in which therapeutics tested in shorter lived species with greater anabolic imbalance will be less effective in humans.

衰老和疾病的进化医学和生活史视角:权衡、功能亢进和不匹配。
上个世纪慢性病的增加给全球带来了重大的健康和经济负担。在这里,我们运用进化医学和生活史理论来更好地理解它们的发展。我们强调了生长和增殖(合成代谢)与维持和休眠(分解代谢)之间不平衡的代谢轴,重点讨论了包括IGF-1、mTOR、AMPK和Klotho在内的主要机制。我们还将这条轴与衰老的功能亢进理论联系起来,该理论同样暗示了衰老和疾病中的合成代谢机制,如mTOR。接下来,我们强调脑-体能量守恒模型,该模型将功能亢进理论与能量权衡联系起来,从而导致功能减退和分解代谢健康风险,如免疫力受损。最后,我们讨论了现代环境错配是如何加剧这一过程的。根据我们的综述,我们讨论了未来的研究方向,以更好地了解健康风险。这包括研究IGF-1、mTOR、AMPK和Klotho,以及它们如何与人类生存人口的健康和老龄化相关,包括生活方式的转变。它还包括了解它们在健康和疾病的发展起源中的作用以及健康差异的社会决定因素。此外,我们还讨论了未来对超长寿命物种进行研究的必要性,以了解它们长寿带来的潜在被低估的权衡和成本。最后,我们考虑了治疗方法的可能影响,包括(i)补偿途径抵消治疗,(ii)“金发女孩区”,过度抑制合成代谢会引入分解代谢健康风险,以及(iii)物种限制,在合成代谢失衡程度较高的短寿命物种中测试的治疗方法对人类的效果较差。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Evolution, Medicine, and Public Health
Evolution, Medicine, and Public Health Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
5.40
自引率
2.70%
发文量
37
审稿时长
8 weeks
期刊介绍: About the Journal Founded by Stephen Stearns in 2013, Evolution, Medicine, and Public Health is an open access journal that publishes original, rigorous applications of evolutionary science to issues in medicine and public health. It aims to connect evolutionary biology with the health sciences to produce insights that may reduce suffering and save lives. Because evolutionary biology is a basic science that reaches across many disciplines, this journal is open to contributions on a broad range of topics.
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