促进衰弱的生理系统。

IF 4.2 2区 医学 Q1 PHYSIOLOGY
Laís R Perazza, Holly M Brown-Borg, LaDora V Thompson
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引用次数: 0

摘要

虚弱是一种复杂的综合征,随着医学的发展,全球人类死亡率不断上升,影响着越来越多的全球人口。我们目前对虚弱的认识来自于实验室和临床研究,这些研究产生了大量的表型信息。但临床前和临床评估工具、多组学方法以及生理和生化方法已为推动该领域的发展奠定了基础。在这篇文章中,我们全面介绍了有关虚弱评估、临床前模型、干预措施、挑战以及临床框架和患病率的主题。我们还确定了可能起作用的核心生物机制,包括线粒体功能障碍、表观遗传学改变和氧化应激,这些反过来又会影响新陈代谢、应激反应以及内分泌和神经肌肉系统。我们回顾了代谢综合征、胰岛素抵抗和内脏肥胖的作用,重点关注葡萄糖稳态、单磷酸腺苷激活蛋白激酶(AMPK)、哺乳动物雷帕霉素靶标(mTOR)和烟酰胺腺嘌呤二核苷酸(NAD+),它们是影响与年龄相关的健康损失的关键因素。我们进一步关注免疫代谢功能障碍如何与氧化应激联系在一起,促进肌肉疏松症,这是导致迟钝、虚弱和疲劳的关键因素。我们探讨了干细胞衰竭所涉及的生物机制,干细胞衰竭会影响再生,并可能导致与虚弱相关的恢复力和压力适应能力下降。此外,我们还概述了衰老生物学与导致虚弱的遗传、生活方式和环境因素之间的相互作用,以及降低风险和减缓疾病进展的潜在治疗目标。© 2022 美国生理学会。Compr Physiol 12:1-46, 2022.
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Physiological Systems in Promoting Frailty.

Physiological Systems in Promoting Frailty.

Frailty is a complex syndrome affecting a growing sector of the global population as medical developments have advanced human mortality rates across the world. Our current understanding of frailty is derived from studies conducted in the laboratory as well as the clinic, which have generated largely phenotypic information. Far fewer studies have uncovered biological underpinnings driving the onset and progression of frailty, but the stage is set to advance the field with preclinical and clinical assessment tools, multiomics approaches together with physiological and biochemical methodologies. In this article, we provide comprehensive coverage of topics regarding frailty assessment, preclinical models, interventions, and challenges as well as clinical frameworks and prevalence. We also identify central biological mechanisms that may be at play including mitochondrial dysfunction, epigenetic alterations, and oxidative stress that in turn, affect metabolism, stress responses, and endocrine and neuromuscular systems. We review the role of metabolic syndrome, insulin resistance and visceral obesity, focusing on glucose homeostasis, adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and nicotinamide adenine dinucleotide (NAD+ ) as critical players influencing the age-related loss of health. We further focus on how immunometabolic dysfunction associates with oxidative stress in promoting sarcopenia, a key contributor to slowness, weakness, and fatigue. We explore the biological mechanisms involved in stem cell exhaustion that affect regeneration and may contribute to the frailty-associated decline in resilience and adaptation to stress. Together, an overview of the interplay of aging biology with genetic, lifestyle, and environmental factors that contribute to frailty, as well as potential therapeutic targets to lower risk and slow the progression of ongoing disease is covered. © 2022 American Physiological Society. Compr Physiol 12:1-46, 2022.

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来源期刊
CiteScore
10.50
自引率
0.00%
发文量
38
审稿时长
6-12 weeks
期刊介绍: Comprehensive Physiology is the most authoritative and comprehensive collection of physiology information ever assembled, and uses the most powerful features of review journals and electronic reference works to cover the latest key developments in the field, through the most authoritative articles on the subjects covered. This makes Comprehensive Physiology a valued reference work on the evolving science of physiology for both researchers and clinicians. It also provides a useful teaching tool for instructors and an informative resource for medical students and other students in the life and health sciences.
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