Mechanisms of Ageing and Development最新文献_第4页

HRasV12 induces apoptosis, not cellular senescence in mouse skeletal myoblasts HRasV12诱导小鼠骨骼肌母细胞凋亡，而非细胞衰老

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-04-28 DOI: 10.1016/j.mad.2025.112066

Shinichiro Suzuki , Takuya Fukunaga , Tatsuya Hayashi , Tatsuro Egawa

引用次数: 0

Differential effects of lifespan-extending genetic manipulations in an animal model of MJD/SCA3 延长寿命的基因操作在MJD/SCA3动物模型中的差异效应

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-04-24 DOI: 10.1016/j.mad.2025.112064

Marta Daniela Costa , Jorge Diogo Da Silva , Dulce Almeida , Joana Pereira-Sousa , Daniela Vilasboas-Campos , Jorge Humberto Fernandes , Andreia Teixeira-Castro , Patrícia Maciel

{"title":"Differential effects of lifespan-extending genetic manipulations in an animal model of MJD/SCA3","authors":"Marta Daniela Costa , Jorge Diogo Da Silva , Dulce Almeida , Joana Pereira-Sousa , Daniela Vilasboas-Campos , Jorge Humberto Fernandes , Andreia Teixeira-Castro , Patrícia Maciel","doi":"10.1016/j.mad.2025.112064","DOIUrl":"10.1016/j.mad.2025.112064","url":null,"abstract":"<div><div>Aging is a natural biological process, but evidence suggests that some aspects of aging can be delayed and reduce the prevalence of neurodegenerative diseases, for which aging is a key risk factor. In a neuronal <em>Caenorhabditis elegans</em> model of a Polyglutamine disease-Spinocerebellar Ataxia Type 3 (SCA3), or Machado-Joseph disease (MJD)- we assessed the hypothesis that delaying aging is neuroprotective, investigating the effect of genetically manipulating multiple lifespan-determinant mechanisms. Lifespan-increasing mutations causing insulin/IGF-1 signaling downregulation, mitochondrial dysfunction, germline ablation and dietary restriction/innate immune activation had distinct impacts on MJD/SCA3 phenotypes, suggesting that not all genetic strategies of stalling aging are equally neuroprotective and challenging the idea that delaying aging is a guaranteed therapy for these diseases. Lifespan-extension improved the SCA3/MJD motor phenotype only when induced by altered nutrient-sensing pathways such as those mediated by insulin/IGF-1 and <em>eat-2</em> signaling, but their effects on neuronal aggregation differed. These pathways exhibited differential proteostasis profiles, but both activated the heat shock response suggesting that they operate through partially independent mechanisms to confer neuroprotection. The therapeutic value of the insulin/IGF-1 downregulation was demonstrated through the chronic treatment of the SCA3/MJD model with an insulin/IGF-1 signaling inhibitor, underscoring the relevance of aging manipulations in guiding therapeutic strategies for these diseases.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"225 ","pages":"Article 112064"},"PeriodicalIF":5.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kaempferol, a widely ingested dietary flavonoid and supplement, enhances biological performance via hormesis, especially for ageing-related processes 山奈酚是一种广泛摄入的膳食类黄酮和补充剂，通过刺激效应提高生物性能，特别是与衰老相关的过程

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-04-24 DOI: 10.1016/j.mad.2025.112065

Edward J. Calabrese , Peter Pressman , A. Wallace Hayes , Linda Baldwin , Evgenios Agathokleous , Harshita Kapoor , Gaurav Dhawan , Rachna Kapoor , Vittorio Calabrese

{"title":"Kaempferol, a widely ingested dietary flavonoid and supplement, enhances biological performance via hormesis, especially for ageing-related processes","authors":"Edward J. Calabrese , Peter Pressman , A. Wallace Hayes , Linda Baldwin , Evgenios Agathokleous , Harshita Kapoor , Gaurav Dhawan , Rachna Kapoor , Vittorio Calabrese","doi":"10.1016/j.mad.2025.112065","DOIUrl":"10.1016/j.mad.2025.112065","url":null,"abstract":"<div><div>Kaempferol is a polyphenol in various fruits and vegetables. It is also commercially developed and sold to consumers as a supplement. It has been extensively assessed in clinical trials for clinical utility based upon its numerous experimentally based chemopreventive properties. Kaempferol has been evaluated at the levels of molecule, cell, and individual animal, showing a broad spectrum of biological effects. Kaempferol-induced hormetic concentration responses are common, being reported in many cell types and biological models for numerous endpoints. While the hormetic effects of kaempferol are biologically diverse, there has been a strong focus on age-related endpoints affecting numerous organ systems and endpoints, indicating that kaempferol is a senolytic agent, showing similar properties as quercetin and fisetin. This paper offers the first integrated evaluation of kaempferol-induced hormetic dose responses, their quantitative characteristics, mechanistic explanations, extrapolative strengths or limitations, and related experimental design, biomedical, therapeutic, ageing, and public health, including ageing related applications.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"225 ","pages":"Article 112065"},"PeriodicalIF":5.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Actinomyces viscosus promotes neuroprotection in C. elegans models of Parkinson’s disease 粘胶放线菌促进秀丽隐杆线虫帕金森病模型的神经保护作用

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-04-19 DOI: 10.1016/j.mad.2025.112061

G. Sophie Ngana , Mercedes A. Di Bernardo , Michael G. Surette , Lesley T. MacNeil

{"title":"Actinomyces viscosus promotes neuroprotection in C. elegans models of Parkinson’s disease","authors":"G. Sophie Ngana , Mercedes A. Di Bernardo , Michael G. Surette , Lesley T. MacNeil","doi":"10.1016/j.mad.2025.112061","DOIUrl":"10.1016/j.mad.2025.112061","url":null,"abstract":"<div><div>Parkinson’s Disease is characterized by selective degeneration of dopaminergic neurons, primarily in the substantia nigra pars compacta, as well as accumulation of alpha-synuclein enriched protein aggregates within neurons. The pathogenesis of PD is still not completely understood, and no treatments exist that alter disease progression. Obvious genetic causes are detected in only a small number of PD patients (5–10 %), suggesting that environmental factors play a significant role the development of PD. Correlative studies suggest that the microbiota could be an important environmental modifier of neurodegeneration. We identified a microbiotal isolate, <em>Actinomyces viscosus,</em> that reduced neurodegeneration in <em>C. elegans</em> expressing a pathological mutant form (G2019S) of leucine-rich repeat kinase 2 (<em>LRRK2</em>) in dopaminergic neurons. <em>A. viscosus</em> also suppressed autophagic dysfunction in these animals and reduced alpha-synuclein aggregation in a synucleinopathy model. Global gene expression analysis revealed increased expression of aspartic cathepsins in response to <em>A. viscosus.</em> Consistent with the involvement of these proteins in neuroprotection, we found that reducing aspartic cathepsin function increased neurodegeneration in the <em>LRRK2</em> transgenic model. Our findings contribute to the current understanding of how the gut microbiota may influence PD, elucidating one potential mechanism of microbiota-mediated neuroprotection.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"225 ","pages":"Article 112061"},"PeriodicalIF":5.3,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

miR-132–3p is down-regulated in plasma and CD171+ extracellular vesicles isolated from patients with mild Alzheimer’s disease 从轻度阿尔茨海默病患者分离的血浆和 CD171+ 细胞外囊泡中下调 miR-132-3p

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-04-17 DOI: 10.1016/j.mad.2025.112063

Matilde Sbriscia , Tatiana Spadoni , Patrizia Ambrogini , Michele Guescini , Rachele Agostini , Laura Graciotti , Francesco Piacenza , Cinzia Giuli , Monia Cecati , Anna Rita Bonfigli , Salvatore Vaiasicca , Marica Pagliarini , Iryna Rusanova , Francesca Fazioli , Jacopo Sabbatinelli , Maria Cristina Albertini , Fabiola Olivieri , Angelica Giuliani

{"title":"miR-132–3p is down-regulated in plasma and CD171+ extracellular vesicles isolated from patients with mild Alzheimer’s disease","authors":"Matilde Sbriscia , Tatiana Spadoni , Patrizia Ambrogini , Michele Guescini , Rachele Agostini , Laura Graciotti , Francesco Piacenza , Cinzia Giuli , Monia Cecati , Anna Rita Bonfigli , Salvatore Vaiasicca , Marica Pagliarini , Iryna Rusanova , Francesca Fazioli , Jacopo Sabbatinelli , Maria Cristina Albertini , Fabiola Olivieri , Angelica Giuliani","doi":"10.1016/j.mad.2025.112063","DOIUrl":"10.1016/j.mad.2025.112063","url":null,"abstract":"<div><div>Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder in aging populations, demands minimally invasive biomarkers for early diagnosis and monitoring. Circulating microRNAs (miRNAs) show promise as such biomarkers. In this study, we examined the levels of five selected miRNAs, implicated in neurodegenerative processes, in plasma and neuron-derived extracellular vesicles (EVs) from cognitively healthy controls (n = 5), and patients with mild (n = 10) and moderate AD (n = 10), stratified by Mini-Mental State Examination (MMSE). miR-23a-3p, miR-223a-3p, and miR-132–3p were significantly downregulated in both plasma and EVs of AD patients, with miR-132–3p emerging as the strongest biomarker candidate for mild AD. Plasma miRNA levels strongly correlated with EV cargo, supporting plasma-based assessments. To validate these findings, miR-132–3p levels were analyzed in expanded cohorts, including cognitively healthy subjects (n = 36), mild AD (n = 37), and moderate AD (n = 40), as well as a cohort of subjects with mild cognitive impairment (MCI, n = 31) and an additional external cohort of cognitively healthy subjects (CTR external, n = 37). Results confirmed miR-132–3p downregulation in AD patients and revealed a significant elevation in MCI individuals, suggesting a potential neuroprotective role in AD early stages. These findings highlight miR-132–3p as a promising, minimally invasive biomarker for early AD diagnosis and disease progression monitoring.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"225 ","pages":"Article 112063"},"PeriodicalIF":5.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Towards defining optimal concentrations of micronutrients in adults to optimize health 确定成人微量营养素的最佳浓度以优化健康

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-04-16 DOI: 10.1016/j.mad.2025.112062

Muhammad Daniel Azlan Mahadzir , Sheryl Tan , Sandalova Elena , Ee Moon Chin , Vandana Garg , Konstantinos Mantantzis , Szabolcs Péter , Andrea B. Maier

{"title":"Towards defining optimal concentrations of micronutrients in adults to optimize health","authors":"Muhammad Daniel Azlan Mahadzir , Sheryl Tan , Sandalova Elena , Ee Moon Chin , Vandana Garg , Konstantinos Mantantzis , Szabolcs Péter , Andrea B. Maier","doi":"10.1016/j.mad.2025.112062","DOIUrl":"10.1016/j.mad.2025.112062","url":null,"abstract":"<div><div>Micronutrients are essential for maintaining physiological homeostasis and optimizing healthspan, defined as the years lived in good health without chronic diseases or disabilities. Despite increasing global life expectancy, improvements in healthspan have not kept pace, partly due to subclinical micronutrient deficiencies that often precede clinical symptoms. The triage theory highlights how micronutrient insufficiencies compromise long-term health by prioritizing critical metabolic functions. Micronutrients such as Vitamins B6, B9, B12, D, and K are particularly crucial to optimizing healthspan, by influencing energy metabolism, neurological health, immune regulation, and bone integrity. Traditional tools like Dietary Reference Intakes (DRIs) provide population-level guidelines but fail to account for individual factors such as genetics, lifestyle, and nutrient interactions. Quantitative assessment of micronutrient concentrations using biomarkers offers a more precise approach but faces challenges, including high costs and limited accessibility. National nutrition surveys demonstrate potential in addressing population-level deficiencies and form the basis for advancing precision supplementation strategies to improve health outcomes and extend healthspan by defining optimal micronutrient concentrations. Future efforts should aim to establish evidence-based thresholds for optimal micronutrient concentrations by integrating biomarker data with clinical outcomes, genetic profiles, and lifestyle factors, providing a framework to guide personalized and population-level supplementation strategies.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"225 ","pages":"Article 112062"},"PeriodicalIF":5.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

miR-34a-5p/MARCHF8/ADAM10 axis in the regulation of vascular endothelial cell dysfunction and senescence miR-34a-5p/MARCHF8/ADAM10轴参与血管内皮细胞功能障碍和衰老的调控

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-04-11 DOI: 10.1016/j.mad.2025.112060

Zonghao Qian , Yuzhen Huang , Ni Yang , Ziwei Fang , Yucong Zhang , Yi Huang , Mandi Luo , Tianyi Ji , Zuoguan Chen , Shang Gao , Yongjun Li , Jinhua Yan , Dingsheng Jiang , Lei Ruan , Anding Liu , Cuntai Zhang , Le Zhang

{"title":"miR-34a-5p/MARCHF8/ADAM10 axis in the regulation of vascular endothelial cell dysfunction and senescence","authors":"Zonghao Qian , Yuzhen Huang , Ni Yang , Ziwei Fang , Yucong Zhang , Yi Huang , Mandi Luo , Tianyi Ji , Zuoguan Chen , Shang Gao , Yongjun Li , Jinhua Yan , Dingsheng Jiang , Lei Ruan , Anding Liu , Cuntai Zhang , Le Zhang","doi":"10.1016/j.mad.2025.112060","DOIUrl":"10.1016/j.mad.2025.112060","url":null,"abstract":"<div><div>Vascular aging is a key driver of age-related cardiovascular and metabolic diseases, with endothelial dysfunction and senescence as a central mechanism. In our recent study, we observed elevated ADAM10 protein levels in senescent endothelial cells, which worsened endothelial dysfunction and senescence. However, the regulatory mechanisms controlling ADAM10 expression are poorly understood. In this study, we show that ADAM10 undergoes post-transcriptional modification in senescent human umbilical vein endothelial cells (HUVECs), with the E3 ubiquitin ligase MARCHF8 predicted to facilitate its ubiquitination-dependent degradation. We also found that MARCHF8 expression was significantly reduced in senescent HUVECs. Knockdown of MARCHF8 in young HUVECs induced endothelial senescence and impaired key endothelial functions, including migration, proliferation, angiogenesis, and nitric oxide production. Conversely, overexpression of MARCHF8 in senescent HUVECs ameliorated senescence-associated dysfunctions. RNA sequencing analysis revealed that MARCHF8 knockdown disrupted pathways linked to cell senescence and atherosclerosis. In vivo, MARCHF8 overexpression in high-fat diet-fed <em>apoE</em><sup>-/-</sup> mice reduced plasma interleukin-6 levels and attenuated atherosclerosis progression. Additionally, miR-34a-5p upregulation in senescence inhibited MARCHF8 expression, compromising its protective effects in delaying endothelial senescence. Collectively, these findings reveal a novel miR-34a-5p/MARCHF8/ADAM10 axis in vascular endothelial senescence, positioning MARCHF8 as a potential biomarker and therapeutic target for vascular aging and related diseases.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"225 ","pages":"Article 112060"},"PeriodicalIF":5.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ANRIL modulates endothelial senescence and angiogenesis through SASP-driven miR146a regulation in age-related vascular dysfunction ANRIL通过sasp驱动的miR146a调控年龄相关血管功能障碍，调节内皮细胞衰老和血管生成

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-04-11 DOI: 10.1016/j.mad.2025.112058

Kechuan Lin , Xin Luo , Can Du , Chenzhe Zuo , Zhenyu Li , Guogang Zhang , Chuanchang Li , Lingping Zhu

{"title":"ANRIL modulates endothelial senescence and angiogenesis through SASP-driven miR146a regulation in age-related vascular dysfunction","authors":"Kechuan Lin , Xin Luo , Can Du , Chenzhe Zuo , Zhenyu Li , Guogang Zhang , Chuanchang Li , Lingping Zhu","doi":"10.1016/j.mad.2025.112058","DOIUrl":"10.1016/j.mad.2025.112058","url":null,"abstract":"<div><div>Vascular aging, marked by endothelial cell (EC) dysfunction and compromised angiogenesis, is a central driver of age-related ischemic diseases. Although lncRNAs have emerged as pivotal regulators of endothelial function, their specific roles in endothelial aging remain enigmatic. In this study, we identify the lncRNA ANRIL as a crucial modulator of endothelial dysfunction during aging. By analyzing publicly available lncRNA sequencing datasets comparing young and old ECs, we pinpointed ANRIL and validated its role through a replicative senescence model in human umbilical vein ECs (HUVECs) and FACS sorting of skeletal muscle ECs from aged mice. While ANRIL showed minimal direct effects on angiogenesis, functional assays and transcriptomic analysis revealed its profound impact on the senescence-associated secretory phenotype (SASP). Remarkably, ANRIL regulates the expression of miR146a in ECs, which is transferred to macrophages, where it inhibits VEGF secretion and disrupts endothelial neovascularization. <em>In vivo</em>, ANRIL downregulation in a murine hindlimb ischemia model significantly enhanced neovascularization and restored blood flow, revealing its therapeutic potential for ischemic diseases. These findings position ANRIL as a novel, potent regulator of endothelial senescence, offering new insights into the molecular basis of vascular aging and suggesting ANRIL as a promising therapeutic target to mitigate age-related vascular dysfunction.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"225 ","pages":"Article 112058"},"PeriodicalIF":5.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Ageing, metabolomics and palaeoanthropology: What can the fields learn from each other? 老龄化、代谢组学和古人类学：这三个领域可以相互学习什么？

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-04-10 DOI: 10.1016/j.mad.2025.112057

James Cole , Andrew Overall , Jennifer C. French , Matt Grove , Nicolas J.W. Rattray , Nicholas A. Stewart , Richard G.A. Faragher

{"title":"Ageing, metabolomics and palaeoanthropology: What can the fields learn from each other?","authors":"James Cole , Andrew Overall , Jennifer C. French , Matt Grove , Nicolas J.W. Rattray , Nicholas A. Stewart , Richard G.A. Faragher","doi":"10.1016/j.mad.2025.112057","DOIUrl":"10.1016/j.mad.2025.112057","url":null,"abstract":"<div><div>Growing old is the major risk factor for hundreds of distinct conditions. Thus, ageing of the global population will pose major social, medical, and economic challenges unless this ill health can be ameliorated or reversed. Accordingly, it is increasingly clear that cross-disciplinary approaches to understanding ageing, although not essential, allow collaborative teams to develop new methodologies which can accelerate translation of research into interventions. Co-creation of new concepts and technologies also brings reciprocal benefits to the individual disciplines involved. The evolution of human ageing is a case in point. Whilst there is broad consensus concerning the process and factors shaping the evolution of ageing in general their relative contributions to the evolution of human ageing remain less clear. This is due to three distinct factors. The extended genetic bottlenecks to which <em>H. sapiens</em> was exposed until the termination of the last ice age which sharply distinguishes our species from almost all current ageing models. Sociality, which humans share with many, but not all, living primate species; and finally, an extended post reproductive menopausal period which is extremely rare in the biosphere and uniquely long in humans. Accordingly, a symposium on the physiology and demography of early human evolution was organised by the authors at which palaeodemographers, archaeologists, population biologists and geroscientists discussed human ageing. This has generated important interdisciplinary research priorities which could accelerate the development of treatments for older people in the present and transform key aspects of our understanding of the ageing process in the past.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"225 ","pages":"Article 112057"},"PeriodicalIF":5.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Changing landscape of hematopoietic and mesenchymal cells and their interactions during aging and in age-related skeletal pathologies 造血和间充质细胞的变化及其在衰老和与年龄相关的骨骼疾病中的相互作用

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2025-04-10 DOI: 10.1016/j.mad.2025.112059

Abhishek Chandra , Susan F. Law , Robert J. Pignolo

{"title":"Changing landscape of hematopoietic and mesenchymal cells and their interactions during aging and in age-related skeletal pathologies","authors":"Abhishek Chandra , Susan F. Law , Robert J. Pignolo","doi":"10.1016/j.mad.2025.112059","DOIUrl":"10.1016/j.mad.2025.112059","url":null,"abstract":"<div><div>Aging profoundly impacts mesenchymal and hematopoietic lineage cells, including their progenitors—the skeletal stem cells (SSCs) and hematopoietic stem cells (HSCs), respectively. SSCs are crucial for skeletal development, homeostasis, and regeneration, maintaining bone integrity by differentiating into osteoblasts, adipocytes, and other lineages that contribute to the bone marrow (BM) microenvironment. Meanwhile, HSCs sustain hematopoiesis and immune function. With aging, SSCs and HSCs undergo significant functional decline, partly driven by cellular senescence—a hallmark of aging characterized by irreversible growth arrest, secretion of pro-inflammatory factors (senescence associated secretory phenotype, SASP), and impaired regenerative potential. In SSCs, senescence skews lineage commitment toward adipogenesis at the expense of osteogenesis, contributing to increased bone marrow adiposity , reduced bone quality, and osteoporosis. Similarly, aged HSCs exhibit diminished self-renewal, biased differentiation, and heightened inflammation, compromising hematopoietic output and immune function. In this review, we examine the age-related cellular and molecular changes in SSCs and HSCs, their lineage decisions in the aging microenvironment, and the interplay between skeletal and hematopoietic compartments. We also discuss the role of senescence-driven alterations in BM homeostasis and how targeting cellular aging mechanisms may offer therapeutic strategies for mitigating age-related skeletal and hematopoietic decline.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"225 ","pages":"Article 112059"},"PeriodicalIF":5.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0