{"title":"病原体加速人类衰老的特征:分子机制综述。","authors":"Amy D. Proal , Michael B. VanElzakker","doi":"10.1016/j.arr.2025.102865","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102865"},"PeriodicalIF":12.4000,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pathogens accelerate features of human aging: A review of molecular mechanisms\",\"authors\":\"Amy D. Proal , Michael B. VanElzakker\",\"doi\":\"10.1016/j.arr.2025.102865\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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.</div></div>\",\"PeriodicalId\":55545,\"journal\":{\"name\":\"Ageing Research Reviews\",\"volume\":\"112 \",\"pages\":\"Article 102865\"},\"PeriodicalIF\":12.4000,\"publicationDate\":\"2025-08-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ageing Research Reviews\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1568163725002119\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ageing Research Reviews","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1568163725002119","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Pathogens accelerate features of human aging: A review of molecular mechanisms
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.
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.