Pathogens accelerate features of human aging: A review of molecular mechanisms

IF 12.4 1区 医学 Q1 CELL BIOLOGY
Amy D. Proal , Michael B. VanElzakker
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引用次数: 0

Abstract

Many models of aging assume that processes such as cellular senescence or epigenetic alteration occur under sterile conditions. However, humans sustain infection with viral, bacterial, fungal, and parasite pathogens across the course of a lifetime, many of which are capable of long-term persistence in host tissue and nerves. These pathogens—especially members of the human virome like herpesviruses, as well as intracellular bacteria and parasites—express proteins and metabolites capable of interfering with host immune signaling, mitochondrial function, gene expression, and the epigenetic environment. This paper reviews these and other key mechanisms by which infectious agents can accelerate features of human aging. This includes hijacking of host mitochondria to gain replication substrates, or the expression of proteins that distort the signaling of host longevity-regulating pathways. We further delineate mechanisms by which pathogen activity contributes to age-related disease development: for example, Alzheimer’s amyloid-β plaque can act as an antimicrobial peptide that forms in response to infection. Overall, because many pathogens dysregulate mTOR, AMPK, or related immunometabolic signaling, healthspan interventions such as low-dose rapamycin, metformin, glutathione, and NAD+ may exert part of their effect by controlling persistent infection. The lack of diagnostics capable of detecting tissue-resident pathogen activity remains a critical bottleneck. Emerging tools—such as ultrasensitive protein assays, cfRNA metagenomics, and immune repertoire profiling—may enable integration of pathogen detection into biological age tracking. Incorporating infection into aging models is essential to more accurately characterize drivers of senescence and to optimize therapeutic strategies that target both host and microbial contributors to aging.
病原体加速人类衰老的特征:分子机制综述。
许多衰老模型假设细胞衰老或表观遗传改变等过程是在无菌条件下发生的。然而,人类在一生中会持续感染病毒、细菌、真菌和寄生虫病原体,其中许多病原体能够在宿主组织和神经中长期存在。这些病原体——尤其是人类病毒组的成员,如疱疹病毒,以及细胞内细菌和寄生虫——表达能够干扰宿主免疫信号、线粒体功能、基因表达和表观遗传环境的蛋白质和代谢物。本文综述了这些和其他关键机制,传染性病原体可以加速人类衰老的特征。这包括劫持宿主线粒体以获得复制底物,或表达扭曲宿主长寿调节途径信号的蛋白质。我们进一步描述了病原体活性促进年龄相关疾病发展的机制:例如,阿尔茨海默病淀粉样蛋白-β斑块可以作为一种抗菌肽,在感染反应中形成。总的来说,由于许多病原体失调mTOR、AMPK或相关的免疫代谢信号,健康干预如低剂量雷帕霉素、二甲双胍、谷胱甘肽和NAD+可能通过控制持续感染发挥部分作用。缺乏能够检测组织驻留病原体活性的诊断仍然是一个关键的瓶颈。新兴的工具,如超灵敏蛋白检测、cfRNA宏基因组学和免疫库谱分析,可能使病原体检测与生物年龄追踪相结合。将感染纳入衰老模型对于更准确地表征衰老驱动因素和优化针对宿主和微生物衰老贡献者的治疗策略至关重要。
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来源期刊
Ageing Research Reviews
Ageing Research Reviews 医学-老年医学
CiteScore
19.80
自引率
2.30%
发文量
216
审稿时长
55 days
期刊介绍: With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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