Mechanisms of Ageing and Development最新文献

{"title":"Mangiferin protects mesenchymal stem cells against DNA damage and cellular aging via SIRT1 activation","authors":"Gyeong Min Lim ,&nbsp;Gwang-Won Cho","doi":"10.1016/j.mad.2025.112038","DOIUrl":"10.1016/j.mad.2025.112038","url":null,"abstract":"<div><div>The protective effects of mangiferin (MAG) against etoposide- and high glucose (HG)–induced DNA damage and aging were investigated in human bone marrow-mesenchymal stem cells (hBM-MSCs). Etoposide, a topoisomerase II inhibitor, was used to induce double-strand breaks (DSBs) in hBM-MSCs, resulting in increased genotoxicity, elevated levels of the DNA damage sensor ATM and CDKN1A, and decreased levels of the aging markers H3 and H4. MAG activated AMPK and SIRT1, thus protecting against DSB-induced damage. Following long-term exposure to HG, MAG significantly mitigated DNA damage and delayed cellular aging, as evidenced by the preservation of H3, H4, LMNB1, and SIRT1 mRNA levels and reduction in γ-H2AX foci and DSBs. Furthermore, MAG improved genome stability, as indicated by decreased LINE1 expression and increased levels of the heterochromatin marker TRIM28, thereby maintaining H3K9me3 levels. MAG and metformin treatment enhanced cell proliferation, reduced senescence-associated β-galactosidase staining, and lowered the levels of the senescence-associated secretory phenotype factors IL-1A, IL-1B, IL-6, IL-8, CCL2, and CCL20 and senescence marker CDKN1A, CDKN2A and p53. MAG may reduce DNA damage and delay aging in hBM-MSCs under HG conditions, highlighting their potential as therapeutic agents for aging-related diseases.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112038"},"PeriodicalIF":5.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059729","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":"Deciphering the role of cytokines in aging: Biomarker potential and effective targeting","authors":"Panagiotis Poulios,&nbsp;Stamoulis Skampouras,&nbsp;Christina Piperi","doi":"10.1016/j.mad.2025.112036","DOIUrl":"10.1016/j.mad.2025.112036","url":null,"abstract":"<div><div>Aging is often characterized by chronic inflammation, immune system dysregulation, and cellular senescence with chronically elevated levels of pro-inflammatory cytokines. These small glycoproteins are mainly secreted by immune cells, mediating intercellular communication and immune system modulation through inflammatory signaling. Their pro- and anti-inflammatory effects make them a noteworthy research topic as well as a promising ally in combating inflammation and the aging process. Cytokines exert a synergistic role in aging and disease and may prove useful biomarkers of tissue-specific dysregulation, disease diagnosis and monitoring, presenting potential therapeutic options as anti-inflammatory and senolytic medications. In this review, we address the cellular and molecular mechanisms implicating cytokines in the aging process and related diseases, highlighting their biomarker potential. We focus on the current therapeutic strategies, including specific pharmaceutical agents, supplements, a balanced diet, and healthy habits such as exercise, stress management, and caloric restriction.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112036"},"PeriodicalIF":5.3,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008064","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":"Corrigendum to “Characterization of a natural model of adult mice with different rate of aging” [Mech. Ageing Dev. 222 (2024), 111991]","authors":"Judith Félix ,&nbsp;Estefanía Díaz-Del Cerro ,&nbsp;Antonio Garrido ,&nbsp;Mónica De la Fuente","doi":"10.1016/j.mad.2025.112027","DOIUrl":"10.1016/j.mad.2025.112027","url":null,"abstract":"","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112027"},"PeriodicalIF":5.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008085","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":"The effect of torque teno virus (TTV) infection on clinical outcomes, genomic integrity, and mortality in COPD patients","authors":"Patrizia Russo ,&nbsp;Francesca Milani ,&nbsp;Dolores Limongi ,&nbsp;Carla Prezioso ,&nbsp;Federica Novazzi ,&nbsp;Francesca Drago Ferrante ,&nbsp;Fabrizio Maggi ,&nbsp;Guido Antonelli ,&nbsp;Stefano Bonassi","doi":"10.1016/j.mad.2024.112024","DOIUrl":"10.1016/j.mad.2024.112024","url":null,"abstract":"<div><h3>Introduction</h3><div>Torque Teno Virus (TTV), an \"orphan\" virus with unclear pathology, has been associated with various diseases and immune dysfunctions. This study investigates the link between TTV viremia and clinical markers in patients with severe to very severe COPD undergoing respiratory rehabilitation.</div></div><div><h3>Methods</h3><div>We analyzed 102 elderly COPD patients, stratified by TTV viremia levels (&lt; or ≥ 4 log10 copies/mL). Clinical markers—including mortality, inflammatory-oxidative parameters (Lymphocyte/Monocyte, Neutrophil/Lymphocyte, and Platelet/Lymphocyte ratios), IL-6 (measured via ELISA assay), and DNA damage (assessed via comet assay)—were evaluated.</div></div><div><h3>Results</h3><div>Of the patients, 62.75 % had TTV viremia levels &gt; 4 log₁₀ copies/mL. No associations were found between TTV levels and sex or obesity. However, higher TTV viremia correlated with increased DNA damage and significantly lower 5-year survival probability.</div></div><div><h3>Conclusion</h3><div>Patients with TTV levels ≥ 4 log₁₀ copies/mL exhibited the lowest survival probability, though DNA damage emerged as a stronger determinant of outcomes. This study raises key scientific questions on the role of TTV in COPD. Specifically, it explores whether TTV may serve as a potential marker for poor prognosis in COPD and whether rehabilitation strategies for these patients could be customized based on DNA damage and/or viremia.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112024"},"PeriodicalIF":5.3,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008067","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":"The role of the LINC complex in ageing and microgravity","authors":"Ivana Lansweers ,&nbsp;Sharon van Rijthoven ,&nbsp;Jack J.W.A. van Loon","doi":"10.1016/j.mad.2025.112028","DOIUrl":"10.1016/j.mad.2025.112028","url":null,"abstract":"<div><div>The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex plays a crucial role in connecting the nuclear envelope to the cytoskeleton, providing structural support to the nucleus and facilitating mechanical signaling between the extracellular environment and the nucleus. Research in mechanobiology onboard the International Space Station (ISS) and in simulated microgravity (SMG) highlight the importance of gravity in functional mechanotransduction. Although the altered gravity research regarding mechanobiology has been greatly focused on the cytoskeleton and the extracellular matrix (ECM), recent research demonstrates that SMG also induces changes in nuclear mechanics and gene expression patterns, which have been shown to be LINC complex dependent. Additionally, dysregulation of the LINC complex disrupts nuclear integrity which leads to nuclear shape abnormalities in both Hutchinson-Gilford Progeria Syndrome (HGPS) and aged cells, which highlights the significance of the LINC complex and related proteins in ageing and age-related disorders. Interestingly, as the effects of spaceflight closely resemble those found in the elderly, the microgravity environment seems to induce an accelerated ageing phenotype in astronauts. Therefore, this review will explore the role of the LINC complex and related proteins in ageing and in microgravity, to further elucidate the interplay between loss of gravitational loading and ageing.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112028"},"PeriodicalIF":5.3,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008069","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":"Insights into age-related osteoporosis from senescence-based preclinical models and human accelerated aging paradigms","authors":"Robert J. Pignolo ,&nbsp;Abhishek Chandra","doi":"10.1016/j.mad.2025.112025","DOIUrl":"10.1016/j.mad.2025.112025","url":null,"abstract":"<div><div>Preclinical models of age-related osteoporosis have been developed based on the accumulation and clearance of senescent cells. The former include animal models based on telomere dysfunction and focal radiation; the latter based on genetic and pharmacological targeting (i.e., removal) of senescent cells. The weight of evidence using these models suggests that cellular senescence plays a key role in the pathophysiology of aging-onset bone loss with the senescence-associated secretory phenotype (SASP) mediating local and systemic deleterious effects on the skeleton. Mitochondrial dysfunction has also been implicated in senescence and age-related comorbidities, including osteoporosis, and knock-in mutations in the mtDNA polymerase gamma (Polg) gene in mice may recapitulate similar respiratory chain complex defects in aged individual with osteoporosis. This and other contributions to senile osteoporosis may also be identified by the careful evaluation of non-genetic paradigms of human accelerated aging. Premature aging syndromes, especially those with a prominent bone loss phenotype, include clinical scenarios of skeletal unloading, premature ovarian failure and survival from childhood cancers. These non-hereditary progeroid syndromes implicate the involvement of lineage switching to an adipogenic fate, inhibition of Wnt signaling, increased osteoclastogenesis and activation frequency of osteoclasts, as well as the substantial burden of senescent cell accumulation.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112025"},"PeriodicalIF":5.3,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979052","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":"Prenatal glucocorticoid exposure and congenital abdominal wall defects: Involvement of CXCR4 – SDF-1 signaling","authors":"Martin Bablok ,&nbsp;Gabriela Morosan-Puopolo ,&nbsp;Imadeldin Yahya ,&nbsp;Morris Gellisch ,&nbsp;Matthias Nissen ,&nbsp;Jochen Hubertus ,&nbsp;Beate Brand-Saberi","doi":"10.1016/j.mad.2024.112008","DOIUrl":"10.1016/j.mad.2024.112008","url":null,"abstract":"<div><div>Developmental defects of the ventral abdominal wall, such as gastroschisis, have been associated with prenatal stress exposure. To investigate this further, dexamethasone (DEX), a synthetic glucocorticoid, was administered to fertilized chicken eggs on day 1 of incubation to simulate stress, and embryonic development was subsequently analyzed through in-situ hybridization, immunohistochemistry, and histological methods. Significant developmental abnormalities were displayed by DEX-treated embryos, including open abdomens, reduced MYOG expression in the abdominal wall, and disrupted muscle fiber formation, as indicated by altered Myosin heavy chain patterns. Additionally, early markers of muscle development, such as Pax3, and the CXCR4-SDF-1 signaling axis, crucial for the migration of myogenic precursors of the dermomyotome, were markedly affected. Significant alterations in the expression of mesenchymal markers, including Vimentin and Fibronectin in the lateral plate mesoderm, were observed, alongside alterations in Pitx2, BMP4 and TFAP2A expression. Importantly, a downregulation of Glucocorticoid Receptors was identified, emphasizing the chronic stress exposure. These results provide critical insights into how DEX interferes with key developmental pathways, particularly those involving chemokines like CXCR4 and SDF-1, and other markers of mesodermal differentiation. An advancement in the understanding of the mechanisms underlying ventral abdominal wall defects in the context of prenatal stress is provided by this research, with potential implications for preventing these congenital anomalies.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112008"},"PeriodicalIF":5.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695613","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":"In reviewing the emerging biomarkers of human inflammatory bowel disease (IBD): Endothelial progenitor cells (EPC) and their vesicles as potential biomarkers of cardiovascular manifestations and targets for personalized treatments","authors":"Carmela Rita Balistreri","doi":"10.1016/j.mad.2024.112006","DOIUrl":"10.1016/j.mad.2024.112006","url":null,"abstract":"<div><div>Inflammatory bowel diseases (IBD) are chronic inflammatory and pathological conditions of the gastrointestinal tract, which include two main clinical subtypes: Crohn's disease (CD) and ulcerative colitis (UC). IBDs show an increase in their age-standardized global incidence rate worldwide, with no gender differences, although the age-standardized mortality rate has decreased over the years. Indeed, thanks to recent therapies with novel mechanisms of action, including those with biologics and small molecules, it has been possible to reduce the mortality rate of IBDs. However, a significant percentage of IBD patients remain refractory to these multiple advanced therapies. Therefore, another challenge of IBD research remains the development of novel therapies with novel agents or cells that could improve the quality of life and outcome of IBD patients. Furthermore, another aspect to be studied in IBDs is not only the high risk of progression not only to neoplastic transformation but also to the development of cardiovascular disease (CVD). Consequently, 25–40 % of IBD patients present with cardiovascular manifestations. Here, we propose that the altered number and functions of endothelial progenitor cells (EPCs) may represent one of the crucial mechanisms associated with incomplete/delayed healing of IBD and may offer the possibility of using them, as well as their vesicles and content, as novel biomarkers and potential candidates of cell therapy for IBD. The advantages and limitations are extensively described and discussed.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 112006"},"PeriodicalIF":5.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693285","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":"Unlocking diagnosis of sarcopenia: The role of circulating biomarkers – A clinical systematic review","authors":"F. Veronesi ,&nbsp;F. Salamanna ,&nbsp;V. Borsari ,&nbsp;A. Ruffilli ,&nbsp;C. Faldini ,&nbsp;G. Giavaresi","doi":"10.1016/j.mad.2024.112005","DOIUrl":"10.1016/j.mad.2024.112005","url":null,"abstract":"<div><div>Sarcopenia, the gradual loss of muscle mass, strength, and function with age, poses a significant risk to older adults, making early diagnosis crucial for preventing disability and enhancing quality of life. Biomarkers are vital for the early detection, monitoring progression, and assessing the efficacy of treatments for sarcopenia, offering a detailed evaluation of muscle health. This systematic review examined the clinical potential of circulating biomarkers in sarcopenia by analyzing studies up to May 2024 from PubMed, Scopus, Web of Science. A total of 45 studies involving 641,730 patients were reviewed, revealing notable biomarker differences between sarcopenic and non-sarcopenic individuals. Sarcopenic patients exhibited lower levels of certain microRNAs, hemoglobin, albumin, and anti-inflammatory factors, alongside higher levels of red and white blood cells, pro-inflammatory factors, growth factors, matrix proteins, free thyroxine, cortisol, and adiponectin. Additionally, they had lower levels of irisin, free triiodothyronine, and insulin, with reduced phosphatidylcholines and elevated spermidine. The studies were generally of fair to good quality, but due to heterogeneity, a meta-analysis was not feasible. The review underscores the need for standardized biomarkers and diagnostic criteria and suggests that improving outcomes for sarcopenic patients may involve addressing inflammation, metabolic, and hormonal issues through nutrition, medication, and exercise.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 112005"},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623559","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":"p53/HIF-1α regulates neuronal aging and autophagy in spinal cord ischemia/reperfusion injury","authors":"Xingzhen Liu ,&nbsp;Jia Wang ,&nbsp;Kangping Shen ,&nbsp;Wenjie Jin","doi":"10.1016/j.mad.2024.112000","DOIUrl":"10.1016/j.mad.2024.112000","url":null,"abstract":"<div><h3>Objection</h3><div>Spinal cord injury (SCI)-induced hindlimb dysfunction affects the physical and mental health of patients. There is growing evidence suggesting that the recovery capacity of elderly SCI patients is poorer than that of young individuals. However, the specific molecular mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>RNA expression profiles of SCI samples were collected from the GEO database, and key genes involved in the progression of SCI were identified by the limma package in R software. A diagnostic model based on SCIDEG was constructed using LASSO regression analysis. Subsequently, correlation analysis was conducted to identify biological pathways influenced by the key genes. Furthermore, SCI animal models were established in different age groups to examine the expression of relevant genes and verify the molecular mechanism of p53/HIF-1α axis.</div></div><div><h3>Results</h3><div>We initially identified 34 ischemia-hypoxia-related genes potentially involved in the progression of SCI. Subsequently, we constructed a diagnostic model based on SCIDEGs using LASSO regression analysis. This model highlighted 9 key genes (<em>TP53</em>, <em>SFTPA1</em>, <em>MASP2</em>, <em>KRT14</em>, <em>IL9</em>, <em>HIF1A</em>, <em>HGFAC</em>, <em>FUT7</em>, and <em>ALPP</em>), which demonstrated high diagnostic accuracy in both the training set (AUC=1) and the validation set (AUC=0.855). Further cross-analysis with ischemia-reperfusion-related datasets confirmed the involvement of <em>HIF1A</em> and <em>TP53</em>. We also observed significant enrichment of <em>HIF1A</em> in organoids composed of mature neurons, which induced neuronal damage. In subsequent spinal cord injury animal models of different age groups, we found that HIF-1α expression was downregulated in the spinal cord tissues of elderly animals. Additionally, we discovered that TP53 activation induces cellular senescence in aging neurons and suppresses HIF-1α expression and autophagy levels within these cells.</div></div><div><h3>Conclusion</h3><div>In summary, our study suggests that the p53/HIF-1α signaling pathway plays a critical role in regulating neuronal aging and autophagy in the pathogenesis of SCI. Importantly, HIF-1α may represent a promising therapeutic target for SCI treatment.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"222 ","pages":"Article 112000"},"PeriodicalIF":5.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623555","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}