Mechanisms of Ageing and Development最新文献

{"title":"Aging: A struggle for beneficial to overcome negative factors made by muscle and bone","authors":"Steven S. Welc ,&nbsp;Marco Brotto ,&nbsp;Kenneth E. White ,&nbsp;Lynda F. Bonewald","doi":"10.1016/j.mad.2025.112039","DOIUrl":"10.1016/j.mad.2025.112039","url":null,"abstract":"<div><div>Musculoskeletal health is strongly influenced by regulatory interactions of bone and muscle. Recent discoveries have identified a number of key mechanisms through which soluble factors released during exercise by bone exert positive effects on muscle and by muscle on bone. Although exercise can delay the negative effects of aging, these beneficial effects are diminished with aging. The limited response of aged muscle and bone tissue to exercise are accompanied by a failure in bone and muscle communication. Here, we propose that exercise induced beneficial factors must battle changes in circulating endocrine and inflammatory factors that occur with aging. Furthermore, sedentary behavior results in the release of negative factors impacting the ability of bone and muscle to respond to physical activity especially with aging. In this review we report on exercise responsive factors and evidence of modification occurring with aging.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112039"},"PeriodicalIF":5.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422506","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}

{"title":"The EZH2/MCM Complex/hTERT axis facilitates hepatocellular carcinoma progression by inhibiting cellular senescence","authors":"Ziyi Shen ,&nbsp;Yuanhui Wang ,&nbsp;Jie Gao ,&nbsp;Wei Gu ,&nbsp;Ziyi Ren ,&nbsp;Luanqi Xu ,&nbsp;Rui Qian ,&nbsp;Qinyi Miao ,&nbsp;Xiaomeng Hu ,&nbsp;Yan Wu ,&nbsp;Wei Liu ,&nbsp;Yi Cai ,&nbsp;Chunpeng (Craig) Wan ,&nbsp;Yansong Zhu ,&nbsp;Lei Sun ,&nbsp;Tingdong Yan","doi":"10.1016/j.mad.2025.112040","DOIUrl":"10.1016/j.mad.2025.112040","url":null,"abstract":"<div><div>The complex pathogenesis of hepatocellular carcinoma (HCC) limits the effectiveness of current therapies. Through RNA sequencing of cancerous and adjacent non-cancerous tissues from six HCC patients, we identified a significant upregulation of MCM2–7 genes, which encode proteins that form the MCM complex, a DNA helicase involved in DNA replication and cell cycle progression. We focused on MCM2, MCM3, and MCM7, and observed that knockdown of these proteins inhibited HCC cell proliferation. Further analysis revealed a critical regulatory axis involving EZH2, the MCM complex, and hTERT. EZH2 was found to be highly correlated with MCM complex gene expression and directly bound to the MCM gene promoters, regulating their expression. This EZH2/MCM complex/hTERT axis may play a key role in suppressing cellular senescence, thereby promoting HCC progression. Knocking down MCM complex genes reduced hTERT expression, inducing HCC cell senescence and enhancing the therapeutic efficacy of sorafenib. These findings suggest that the EZH2/MCM complex/hTERT axis could serve as a novel therapeutic target for HCC.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112040"},"PeriodicalIF":5.3,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388112","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}

{"title":"Oral frailty indicators and cardio- and cerebrovascular diseases in older age: A systematic review","authors":"Vittorio Dibello ,&nbsp;Frank Lobbezoo ,&nbsp;Francesco Panza ,&nbsp;Madia Lozupone ,&nbsp;Alberto Pilotto ,&nbsp;Vitalba Vitale ,&nbsp;Carlo Custodero ,&nbsp;Antonio Dibello ,&nbsp;Vincenzo Vertucci ,&nbsp;Antonio Daniele ,&nbsp;Daniele Manfredini ,&nbsp;Vincenzo Solfrizzi","doi":"10.1016/j.mad.2024.112010","DOIUrl":"10.1016/j.mad.2024.112010","url":null,"abstract":"<div><div>Oral health indicators may contribute to the oral frailty phenotype, an age-related gradual loss of oral function together with a decline in cognitive and physical functions. The present systematic review synthetized current knowledge on the associations of oral frailty indicators and major cardio- and cerebrovascular diseases in older age, including coronary heart disease (CHD), arteriosclerosis, arrhythmias, hypertension, cardiovascular diseases not otherwise specified (NOS), and stroke. The study is registered on PROSPERO-(CRD42023397932). From database inception to March 31, 2024, six different electronic databases were consulted assessing the eligibility of 50,005 records against the inclusion criteria and 20 studies on 226,025 older adults were included. Five different indicators of oral frailty (number of teeth, periodontal disease, general oral health, dry mouth, and bite force) were related to cardio- and cerebrovascular diseases. The number of teeth was associated with all the outcomes except hypertension, followed by periodontal disease associated with CHD, arteriosclerosis, hypertension, and stroke. General oral health and dry mouth were associated with CHD/arrhythmias and CHD/stroke, respectively. Finally, bite force was associated only with cardiovascular diseases NOS. The present findings could help to assess the contribution of each oral frailty indicator to the development of cardio- and cerebrovascular diseases in older age.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112010"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770414","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}

{"title":"The impact of sleep and exercise on brain atrophy in mild cognitive impairment","authors":"Maamoon Mian ,&nbsp;Jihane Tahiri ,&nbsp;Saadeddine Habbal ,&nbsp;Fatima Aftan ,&nbsp;P. Hemachandra Reddy","doi":"10.1016/j.mad.2024.112023","DOIUrl":"10.1016/j.mad.2024.112023","url":null,"abstract":"<div><div>Chronic sleep deprivation and lack of physical exercise may have detrimental effects on overall health, particularly in terms of brain health, with significant implications for cognitive function and well-being. This review explores the impact of chronic sleep deprivation and physical exercise on brain atrophy in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Drawing insights from 40 selected studies, the review synthesizes evidence on these lifestyle factors' correlations with neurodegenerative changes. Chronic sleep deprivation disrupts circadian rhythms and neurochemical pathways, potentially accelerating brain atrophy, while physical exercise preserves brain structure by enhancing vascular health, reducing inflammation, and supporting synaptic plasticity, particularly in regions like the hippocampus. Results highlight distinct patterns of brain atrophy in AD and MCI, underscoring the potential for targeted interventions to mitigate cognitive decline. Understanding the relationship between sleep disruption and brain health provides insights into strategies for possibly delaying neurodegenerative diseases like MCI, which represents a milder form of Alzheimer's, and AD. The findings underscore the potential utility of integrating sleep therapy and physical exercise interventions in clinical practice for early detection of mild cognitive impairment and potentially delaying disease progression. This integrated approach has been found to promote healthy aging, reduce atrophy rates, and enhance cognitive resilience across aging populations.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112023"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895687","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}

{"title":"Senolytics rejuvenate aging cardiomyopathy in human cardiac organoids","authors":"Mariangela Scalise ,&nbsp;Eleonora Cianflone ,&nbsp;Claudia Quercia ,&nbsp;Loredana Pagano ,&nbsp;Antonio Chiefalo ,&nbsp;Antonio Stincelli ,&nbsp;Annalaura Torella ,&nbsp;Barbara Puccio ,&nbsp;Gianluca Santamaria ,&nbsp;Hiram P. Guzzi ,&nbsp;Pierangelo Veltri ,&nbsp;Antonella De Angelis ,&nbsp;Konrad Urbanek ,&nbsp;Georgina M. Ellison-Hughes ,&nbsp;Daniele Torella ,&nbsp;Fabiola Marino","doi":"10.1016/j.mad.2024.112007","DOIUrl":"10.1016/j.mad.2024.112007","url":null,"abstract":"<div><h3>Background</h3><div>Human cardiac organoids closely replicate the architecture and function of the human heart, offering a potential accurate platform for studying cellular and molecular features of aging cardiomyopathy. Senolytics have shown potential in addressing age-related pathologies but their potential to reverse aging-related human cardiomyopathy remains largely unexplored.</div></div><div><h3>Methods</h3><div>We employed human iPSC-derived cardiac organoids (hCOs/hCardioids) to model doxorubicin(DOXO)-induced cardiomyopathy in an aged context. hCardioids were treated with DOXO and subsequently with a combination of two senolytics: dasatinib (D) and quercetin (Q).</div></div><div><h3>Results</h3><div>DOXO-treated hCardioids exhibited significantly increased oxidative stress, DNA damage (pH2AX), cellular senescence (p16^INK4A) and decreased cell proliferation associated with a senescence-associated secretory phenotype (SASP). DOXO-treated hCardioids were considerably deprived of cardiac progenitors and displayed reduced cardiomyocyte proliferation as well as contractility. These distinctive aging-associated characteristics were confirmed by global RNA-sequencing analysis. Treatment with D+Q reversed these effects, reducing oxidative stress and senescence markers, alleviating SASP, and restoring hCardioids viability and function. Additionally, senolytics replenished cardiac progenitors and reversed the cardiomyocyte proliferation deficit.</div></div><div><h3>Conclusions</h3><div>Doxorubicin triggers an age-associated phenotype in hCardioids reliably modelling the main cellular and molecular features of aging cardiomyopathy. Senescence is a key mechanism of the aged-hCOs phenotype as senolytics rejuvenated aged-hCardioids restoring their structure and function while reverting the age-associated regenerative deficit.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112007"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell analysis of human peripheral blood reveals high immune response activity in successful ageing individuals","authors":"Yu Wang ,&nbsp;Yuxing Zhang ,&nbsp;Ge Gong ,&nbsp;Quanzhong Liu ,&nbsp;Liangyu Li ,&nbsp;Mingjiong Zhang ,&nbsp;Shuping Shen ,&nbsp;Ran Wang ,&nbsp;Jianqing Wu ,&nbsp;Wei Xu","doi":"10.1016/j.mad.2024.112011","DOIUrl":"10.1016/j.mad.2024.112011","url":null,"abstract":"<div><div>Beneficial remodeling of the immune system in successful ageing individuals (centenarians and supercentenarians) is critical for healthy ageing. However, mechanisms for dynamic regulation of immunity during ageing remain unclear. We use single-cell RNA sequencing (scRNA-seq) as an analytical strategy to study the dynamic regulation of immunity during aging and its molecular mechanisms at the single-cell level. We performed an integrative analysis of 87,215 peripheral blood mononuclear cells, from seven supercentenarians, three centenarians, and four elderly controls, generated by single-cell transcriptomics complemented with fluorescence-activated cell sorting. Animals experiments were also conducted to validate the makers of healthy aging found by our bioinformatic analysis and further explore the dynamic of immune changes during aging process. We found that CD8⁺ effector memory T cells and terminally differentiated B cells were enriched in the longevity group (centenarians and supercentenarians), whereas naïve T cells and Tregs were enriched in elderly controls. CD56^dim NK cells in the longevity group activated Fc-γ receptor signaling. The higher antigen-presenting ability of CD14⁺ monocytes in the longevity group and the CellChat analysis indicated that CD14⁺ monocytes might assist active T and B cells. Here, we revealed the adaptive immune remodeling geromarkers of immunosenescence in centenarians and supercentenarians, which could be considered as biomarkers of healthy aging, and might help sustain immune responses and achieve exceptional longevity.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112011"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770420","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}

{"title":"Role of chemokines in aging and age-related diseases","authors":"Jitendra Kumar Chaudhary ,&nbsp;Ajay Kumar Danga ,&nbsp;Anita Kumari ,&nbsp;Akshay Bhardwaj ,&nbsp;Pramod C. Rath","doi":"10.1016/j.mad.2024.112009","DOIUrl":"10.1016/j.mad.2024.112009","url":null,"abstract":"<div><div>Chemokines (chemotactic cytokines) play essential roles in developmental process, immune cell trafficking, inflammation, immunity, angiogenesis, cellular homeostasis, aging, neurodegeneration, and tumorigenesis. Chemokines also modulate response to immunotherapy, and consequently influence the therapeutic outcome. The mechanisms underlying these processes are accomplished by interaction of chemokines with their cognate cell surface G protein-coupled receptors (GPCRs) and subsequent cellular signaling pathways. Chemokines play crucial role in influencing aging process and age-related diseases across various tissues and organs, primarily through inflammatory responses (inflammaging), recruitment of macrophages, and orchestrated trafficking of other immune cells. Chemokines are categorized in four distinct groups based on the position and number of the N-terminal cysteine residues; namely, the CC, CXC, CX3C, and (X)C. They mediate inflammatory responses, and thereby considerably impact aging process across multiple organ-systems. Therefore, understanding the underlying mechanisms mediated by chemokines may be of crucial importance in delaying and/or modulating the aging process and preventing age-related diseases. In this review, we highlight recent progress accomplished towards understanding the role of chemokines and their cellular signaling pathways involved in aging and age-relaed diseases of various organs. Moreover, we explore potential therapeutic strategies involving anti-chemokines and chemokine receptor antagonists aimed at reducing aging and mitigating age-related diseases. One of the modern methods in this direction involves use of chemokine receptor antagonists and anti-chemokines, which suppress the pro-inflammatory response, thereby helping in resolution of inflammation. Considering the wide-spectrum of functional involvements of chemokines in aging and associated diseases, several clinical trials are being conducted to develop therapeutic approaches using anti-chemokine and chemokine receptor antagonists to improve life span and promote healthy aging.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112009"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780655","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}

{"title":"Aberrant expression of messenger and small noncoding RNAomes in aged skin of rats","authors":"Danyang Zhao ,&nbsp;Yu Wang ,&nbsp;Chuandong Wang ,&nbsp;Yaxin Xue ,&nbsp;Hao Lv ,&nbsp;Wei Xu ,&nbsp;Dong Han ,&nbsp;Yu Sun ,&nbsp;Qingfeng Li","doi":"10.1016/j.mad.2024.112022","DOIUrl":"10.1016/j.mad.2024.112022","url":null,"abstract":"<div><div>The exact mechanisms and key functional molecules involved in skin ageing remain largely unknown. Studies linking the expression of messenger RNAs (mRNAs) and small noncoding RNAs (sncRNAs) to skin ageing are limited. In this study, we performed RNA sequencing to assess the effects of ageing on the expression of mRNAs and sncRNAs in rat skin. Our results revealed that 241 mRNAs, 109 microRNAs (miRNAs), 20 piwi-interacting RNAs (piRNAs), 45 small nucleolar RNAs (snoRNAs), and 7 small nuclear RNAs (snRNAs) were significantly differentially expressed in the skin of aged rats compared to their younger counterparts. Histological validation using RT-qPCR further verified the significant differential expression of 13 mRNAs, 7 miRNAs, 2 piRNAs, 15 snoRNAs, and 1 snRNA. Additionally, several sncRNAs showed differential expression across various tissues, suggesting that they may have broad correlations with ageing. After establishing cellular senescence in skin fibroblasts, we identified 4 mRNAs, 4 miRNAs, and 10 snoRNAs that may mediate skin ageing by modulating fibroblast senescence. Notably, overexpression or knockdown of some differentially expressed RNAs in fibroblasts influenced cellular senescence, indicating that these RNAs could play an important role in the skin ageing process. These findings highlight their potential significance for future treatments of age-related skin disorders.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112022"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877387","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}

{"title":"Molecular mechanisms and potential interventions during aging-associated sarcopenia","authors":"Xiaoqin Luo ,&nbsp;Jin Wang ,&nbsp;Qingqing Ju ,&nbsp;Tianyu Li ,&nbsp;Xiuli Bi","doi":"10.1016/j.mad.2024.112020","DOIUrl":"10.1016/j.mad.2024.112020","url":null,"abstract":"<div><div>Sarcopenia, a common condition observed in the elderly, presenting a significant public health challenge due to its high prevalence, insidious onset and diverse systemic effects. Despite ongoing research, the precise etiology of sarcopenia remains elusive. Aging-related processes, which included inflammation, oxidative stress, compromised mitochondrial function and apoptosis, have been implicated in its development. Notably, effective pharmacological treatments for sarcopenia are currently lacking, highlighting the necessity for a deeper understanding of its pathogenesis and causative factors to enable proactive interventions. This article is aimed to provide an extensive overview of the pathogenesis of sarcopenia, along with a summary of current treatment and prevention strategies.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112020"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818579","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}

{"title":"The telomere connection between aging and cancer: The burden of replication stress and dysfunction","authors":"Virginia Boccardi ,&nbsp;Luigi Marano","doi":"10.1016/j.mad.2025.112026","DOIUrl":"10.1016/j.mad.2025.112026","url":null,"abstract":"<div><div>Aging is a complex process that affects individuals at the molecular, cellular, tissue, and systemic levels, arising from the cumulative effects of damage and reduced repair mechanisms. This process leads to the onset of age-related diseases, including cancer, which exhibits increased incidence with age. Telomeres, the protective caps at chromosome ends, play a crucial role in genome stability and are closely connected with aging and age-related disorders. Both excessively short and long telomere lengths may contribute to cancer development when their balance is disrupted. Fragile telomeres, characterized by abnormalities and replication stress, may provide novel insights into the connection between aging and cancer. The accumulation of fragile telomeres, possibly due to intense replicative stress, may represent a key factor. Given the dynamic nature of telomeres, large longitudinal studies are essential for understanding their role in aging and cancer susceptibility, which is crucial for developing effective strategies to promote healthy aging and mitigate cancer risk.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112026"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979055","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}