Mechanisms of Ageing and Development最新文献_第10页

The role of longevity-related genetic variant interactions as predictors of survival after 85 years of age 与长寿相关的遗传变异相互作用对 85 岁后存活率的预测作用。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-03-13 DOI: 10.1016/j.mad.2024.111926

Maja Šetinc , Željka Celinšćak , Luka Bočkor , Matea Zajc Petranović , Anita Stojanović Marković , Marijana Peričić Salihović , Joris Deelen , Tatjana Škarić-Jurić

{"title":"The role of longevity-related genetic variant interactions as predictors of survival after 85 years of age","authors":"Maja Šetinc , Željka Celinšćak , Luka Bočkor , Matea Zajc Petranović , Anita Stojanović Marković , Marijana Peričić Salihović , Joris Deelen , Tatjana Škarić-Jurić","doi":"10.1016/j.mad.2024.111926","DOIUrl":"10.1016/j.mad.2024.111926","url":null,"abstract":"<div>Genome-wide association studies and candidate gene studies have identified several genetic variants that might play a role in achieving longevity. This study investigates interactions between pairs of those single nucleotide polymorphisms (SNPs) and their effect on survival above the age of 85 in a sample of 327 Croatian individuals. Although none of the SNPs individually showed a significant effect on survival in this sample, 14 of the 359 interactions tested (between SNPs not in LD) reached the level of nominal significance (p<0.05), showing a potential effect on late-life survival. Notably, SH2B3 rs3184504 interacted with different SNPs near TERC, TP53 rs1042522 with different SNPs located near the CDKN2B gene, and CDKN2B rs1333049 with different SNPs in FOXO3, as well as with LINC02227 rs2149954. The other interaction pairs with a possible effect on survival were FOXO3 rs2802292 and ERCC2 rs50871, IL6 rs1800795 and GHRHR rs2267723, LINC02227 rs2149954 and PARK7 rs225119, as well as PARK7 rs225119 and PTPN1 rs6067484. These interactions remained significant when tested together with a set of health-related variables that also had a significant effect on survival above 85 years. In conclusion, our results confirm the central role of genetic regulation of insulin signalling and cell cycle control in longevity.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"219 ","pages":"Article 111926"},"PeriodicalIF":5.3,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000265/pdfft?md5=9104fa7f88299f2be2e88baf6a5738fd&pid=1-s2.0-S0047637424000265-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131864","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}

引用次数: 0

Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration 实现个性化的烟酰胺单核苷酸（NMN）补充：烟酰胺腺嘌呤二核苷酸（NAD）浓度

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-29 DOI: 10.1016/j.mad.2024.111917

Ajla Hodzic Kuerec , Weilan Wang , Lin Yi , Rongsheng Tao , Zhigang Lin , Aditi Vaidya , Sohal Pendse , Sornaraja Thasma , Niranjan Andhalkar , Ganesh Avhad , Vidyadhar Kumbhar , Andrea B. Maier

{"title":"Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration","authors":"Ajla Hodzic Kuerec , Weilan Wang , Lin Yi , Rongsheng Tao , Zhigang Lin , Aditi Vaidya , Sohal Pendse , Sornaraja Thasma , Niranjan Andhalkar , Ganesh Avhad , Vidyadhar Kumbhar , Andrea B. Maier","doi":"10.1016/j.mad.2024.111917","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111917","url":null,"abstract":"<div>Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. This is a post-hoc analysis of a double-blinded clinical trial involving 80 generally healthy adults aged 40–65 years. The participants received a placebo or daily 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration, blood biological age, homeostatic model assessment for insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline and after supplement. A significant dose-dependent increase in NAD concentration change (NADΔ) was observed following NMN supplementation, with a large coefficient of variation (29.2–113.3%) within group. The increase in NADΔ was associated with an improvement in the walking distance of 6-minute walk test and the SF-36 score. The median effect dose of NADΔ for the 6-minute walk test and SF-36 score was 15.7 nmol/L (95% CI: 10.9–20.5 nmol/L) and 13.5 nmol/L (95% CI; 10.5–16.5 nmol/L), respectively. Because of the high interindividual variability of the NADΔ after NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalized dosage regimens and optimizing NMN utilization.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111917"},"PeriodicalIF":5.3,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000174/pdfft?md5=596090ef08c0556c0ae9813c959d2a65&pid=1-s2.0-S0047637424000174-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140016076","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}

引用次数: 0

Insights into targeting cellular senescence with senolytic therapy: The journey from preclinical trials to clinical practice 以细胞衰老为靶点的衰老疗法：从临床前试验到临床实践的历程。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-23 DOI: 10.1016/j.mad.2024.111918

Peng Chen , Yulai Wang , Benhong Zhou

引用次数: 0

Common and distinct metabolomic markers related to immune aging in Western European and East African populations 西欧和东非人群中与免疫衰老有关的共同和独特代谢组标记物

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-14 DOI: 10.1016/j.mad.2024.111916

Ozlem Bulut , Godfrey S. Temba , Valerie A.C.M. Koeken , Simone J.C.F.M. Moorlag , L. Charlotte J. de Bree , Vera P. Mourits , Vesla I. Kullaya , Martin Jaeger , Cancan Qi , Niels P. Riksen , Jorge Domínguez-Andrés , Cheng-Jian Xu , Leo A.B. Joosten , Yang Li , Quirijn de Mast , Mihai G. Netea

{"title":"Common and distinct metabolomic markers related to immune aging in Western European and East African populations","authors":"Ozlem Bulut , Godfrey S. Temba , Valerie A.C.M. Koeken , Simone J.C.F.M. Moorlag , L. Charlotte J. de Bree , Vera P. Mourits , Vesla I. Kullaya , Martin Jaeger , Cancan Qi , Niels P. Riksen , Jorge Domínguez-Andrés , Cheng-Jian Xu , Leo A.B. Joosten , Yang Li , Quirijn de Mast , Mihai G. Netea","doi":"10.1016/j.mad.2024.111916","DOIUrl":"https://doi.org/10.1016/j.mad.2024.111916","url":null,"abstract":"<div>In old age, impaired immunity causes high susceptibility to infections and cancer, higher morbidity and mortality, and poorer vaccination efficiency. Many factors, such as genetics, diet, and lifestyle, impact aging. This study aimed to investigate how immune responses change with age in healthy Dutch and Tanzanian individuals and identify common metabolites associated with an aged immune profile. We performed untargeted metabolomics from plasma to identify age-associated metabolites, and we correlated their concentrations with ex-vivo cytokine production by immune cells, DNA methylation-based epigenetic aging, and telomere length. Innate immune responses were impacted differently by age in Dutch and Tanzanian cohorts. Age-related decline in steroid hormone precursors common in both populations was associated with higher systemic inflammation and lower cytokine responses. Hippurate and 2-phenylacetamide, commonly more abundant in older individuals, were negatively correlated with cytokine responses and telomere length and positively correlated with epigenetic aging. Lastly, we identified several metabolites that might contribute to the stronger decline in innate immunity with age in Tanzanians. The shared metabolomic signatures of the two cohorts suggest common mechanisms of immune aging, revealing metabolites with potential contributions. These findings also reflect genetic or environmental effects on circulating metabolites that modulate immune responses.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111916"},"PeriodicalIF":5.3,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000162/pdfft?md5=40a7284951bc886f679842b24682f73b&pid=1-s2.0-S0047637424000162-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139744103","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}

引用次数: 0

Long-COVID-19 autonomic dysfunction: An integrated view in the framework of inflammaging Long-COVID-19 自主神经功能障碍：炎症框架下的综合观点。

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-13 DOI: 10.1016/j.mad.2024.111915

Sergio Giunta , Chiara Giordani , Maria De Luca , Fabiola Olivieri

{"title":"Long-COVID-19 autonomic dysfunction: An integrated view in the framework of inflammaging","authors":"Sergio Giunta , Chiara Giordani , Maria De Luca , Fabiola Olivieri","doi":"10.1016/j.mad.2024.111915","DOIUrl":"10.1016/j.mad.2024.111915","url":null,"abstract":"<div>The recently identified syndrome known as Long COVID (LC) is characterized by a constellation of debilitating conditions that impair both physical and cognitive functions, thus reducing the quality of life and increasing the risk of developing the most common age-related diseases. These conditions are linked to the presence of symptoms of autonomic dysfunction, in association with low cortisol levels, suggestive of reduced hypothalamic-pituitary-adrenal (HPA) axis activity, and with increased pro-inflammatory condition. Alterations of dopamine and serotonin neurotransmitter levels were also recently observed in LC. Interestingly, at least some of the proposed mechanisms of LC development overlap with mechanisms of Autonomic Nervous System (ANS) imbalance, previously detailed in the framework of the aging process. ANS imbalance is characterized by a proinflammatory sympathetic overdrive, and a concomitant decreased anti-inflammatory vagal parasympathetic activity, associated with reduced anti-inflammatory effects of the HPA axis and cholinergic anti-inflammatory pathway (CAP). These neuro-immune-endocrine system imbalanced activities fuel the vicious circle of chronic inflammation, i.e. inflammaging. Here, we refine our original hypothesis that ANS dysfunction fuels inflammaging and propose that biomarkers of ANS imbalance could also be considered biomarkers of inflammaging, recognized as the main risk factor for developing age-related diseases and the sequelae of viral infections, i.e. LC.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111915"},"PeriodicalIF":5.3,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735496","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

WDR23 mediates NRF2 proteostasis and cytoprotective capacity in the hippocampus WDR23 在海马中介导 NRF2 蛋白稳态和细胞保护能力

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-01 DOI: 10.1016/j.mad.2024.111914

Jiahui Liu, Chatrawee Duangjan , Ronald W. Irwin , Sean P. Curran

引用次数: 0

The close relationship between oocyte aging and telomere shortening, and possible interventions for telomere protection 卵母细胞老化与端粒缩短的密切关系，以及保护端粒的可能干预措施

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-02-01 DOI: 10.1016/j.mad.2024.111913

Saffet Ozturk

引用次数: 0

Age-dependent energy metabolism and transcriptome changes in urine-derived stem cells 尿液衍生干细胞随年龄变化的能量代谢和转录组变化

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-01-22 DOI: 10.1016/j.mad.2024.111912

Elisabete Ferreiro , Mariana Monteiro , Francisco Pereira , Cristina Barroso , Conceição Egas , Paula Macedo , Jorge Valero , Vilma A. Sardão , Paulo J. Oliveira

{"title":"Age-dependent energy metabolism and transcriptome changes in urine-derived stem cells","authors":"Elisabete Ferreiro , Mariana Monteiro , Francisco Pereira , Cristina Barroso , Conceição Egas , Paula Macedo , Jorge Valero , Vilma A. Sardão , Paulo J. Oliveira","doi":"10.1016/j.mad.2024.111912","DOIUrl":"10.1016/j.mad.2024.111912","url":null,"abstract":"<div>The global population over 60 years old is projected to reach 1.5 billion by 2050. Understanding age-related disorders and gender-specificities is crucial for a healthy aging. Reliable age-related biomarkers are needed, preferentially obtained through non-invasive methods. Urine-derived stem cells (UDSCs) can be easily obtained, although a detailed bioenergetic characterization, according to the donor aging, remain unexplored. UDSCs were isolated from young and elderly adult women (22–35 and 70–94 years old, respectively). Surprisingly, UDSCs from elderly subjects exhibited significantly higher maximal oxygen consumption and bioenergetic health index than those from younger individuals, evaluated through oxygen consumption rate. Exploratory data analysis methods were applied to engineer a minimal subset of features for the classification and stratification of UDSCs. Additionally, RNAseq of UDSCs was performed to identify age-related transcriptional changes. Transcriptional analysis revealed downregulation of genes related to glucuronidation and estrogen metabolism, and upregulation of inflammation-related genes in UDSCs from elderly individuals. This study demonstrates unexpected differences in the UDSCs’ OCR between young and elderly individuals, revealing improved bioenergetics in concurrent with an aged-like transcriptome signature. UDSCs offer a non-invasive model for studying age-related changes, holding promise for aging research and therapeutic studies.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111912"},"PeriodicalIF":5.3,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0047637424000125/pdfft?md5=27c318b23e96ebea1cf3790fc436fbb9&pid=1-s2.0-S0047637424000125-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139523499","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}

引用次数: 0

Calcium transferring from ER to mitochondria via miR-129/ITPR2 axis controls cellular senescence in vitro and in vivo 钙通过 miR-129/ITPR2 轴从 ER 转移到线粒体，控制体外和体内的细胞衰老

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-01-11 DOI: 10.1016/j.mad.2024.111902

Yue Gao , Lei Xu , Yaru Li , Dandan Qi , Chaofan Wang , Changjiao Luan , Shihui Zheng , Qiu Du , Weili Liu , Guotao Lu , Weijuan Gong , Xingjie Ma

{"title":"Calcium transferring from ER to mitochondria via miR-129/ITPR2 axis controls cellular senescence in vitro and in vivo","authors":"Yue Gao , Lei Xu , Yaru Li , Dandan Qi , Chaofan Wang , Changjiao Luan , Shihui Zheng , Qiu Du , Weili Liu , Guotao Lu , Weijuan Gong , Xingjie Ma","doi":"10.1016/j.mad.2024.111902","DOIUrl":"10.1016/j.mad.2024.111902","url":null,"abstract":"<div>Senescent cells are known to be accumulated in aged organisms. Although the two main characteristics, cell cycle arrest (for dividing cells) and secretion of senescence-associated secretory phenotype (SASP) factors, have been well described, the lack of sufficient senescent markers and incomplete understanding of mechanisms have limited the progress of the anti-senescence field. Calcium transferred from the endoplasmic reticulum (ER) via inositol 1, 4, 5-trisphosphate receptor type 2 (ITPR2) to mitochondria has emerged as a key player during cellular senescence and aging. However, the internal regulatory mechanisms, particularly those of endogenous molecules, remain only partially understood. Here we identified miRNA-129 (miR-129) as a direct repressor of ITPR2. Interestingly, miR-129 controlled a cascade of intracellular calcium signaling, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), DNA damage, and consequently cellular senescence through ITPR2 and mitochondrial calcium uniporter (MCU). In addition, miR-129 was repressed in different senescence models and delayed bleomycin-induced cellular senescence. Importantly, intraperitoneal injection of miR-129 partly postponed bleomycin-accelerated lung aging and natural aging markers as well as reduced immunosenescence markers in mice. Altogether, these findings demonstrated that miR-129 regulated cellular senescence and aging markers via intracellular calcium signaling by directly targeting ITPR2.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111902"},"PeriodicalIF":5.3,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139420706","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

Novel 18-norspirostane steroidal saponins: Extending lifespan and mitigating neurodegeneration through promotion of mitophagy and mitochondrial biogenesis in Caenorhabditis elegans 新型 18-Norspirostane 类固醇皂甙：通过促进线粒体吞噬和线粒体生物生成延长秀丽隐杆线虫的寿命并缓解神经退行性变

IF 5.3 3区医学

Mechanisms of Ageing and Development Pub Date : 2024-01-10 DOI: 10.1016/j.mad.2024.111901

An-Guo Wu , Yuan-Yuan Yong , Chang-Long He , Ya-Ping Li , Xing-Yue Zhou , Lu Yu , Qi Chen , Cai Lan , Jian Liu , Chong-Lin Yu , Da-Lian Qin , Jian-Ming Wu , Xiao-Gang Zhou

{"title":"Novel 18-norspirostane steroidal saponins: Extending lifespan and mitigating neurodegeneration through promotion of mitophagy and mitochondrial biogenesis in Caenorhabditis elegans","authors":"An-Guo Wu , Yuan-Yuan Yong , Chang-Long He , Ya-Ping Li , Xing-Yue Zhou , Lu Yu , Qi Chen , Cai Lan , Jian Liu , Chong-Lin Yu , Da-Lian Qin , Jian-Ming Wu , Xiao-Gang Zhou","doi":"10.1016/j.mad.2024.111901","DOIUrl":"10.1016/j.mad.2024.111901","url":null,"abstract":"<div>Pharmacological strategies to delay aging and combat age-related diseases are increasingly promising. This study explores the anti-aging and therapeutic effects of two novel 18-norspirostane steroidal saponins from Trillium tschonoskii Maxim, namely deoxytrillenoside CA (DTCA) and epitrillenoside CA (ETCA), using Caenorhabditis elegans (C. elegans). Both DTCA and ETCA significantly extended the lifespan of wild-type N2 worms and improved various age-related phenotypes, including muscle health, motility, pumping rate, and lipofuscin accumulation. Furthermore, these compounds exhibited notable alleviation of pathology associated with Parkinson's disease (PD) and Huntington's disease (HD), such as the reduction of α-synuclein and poly40 aggregates, improvement in motor deficits, and mitigation of neuronal damage. Meanwhile, DTCA and ETCA improved the lifespan and healthspan of PD- and HD-like C. elegans models. Additionally, DTCA and ETCA enhanced the resilience of C. elegans against heat and oxidative stress challenges. Mechanistic studies elucidated that DTCA and ETCA induced mitophagy and promoted mitochondrial biogenesis in C. elegans, while genetic mutations or RNAi knockdown affecting mitophagy and mitochondrial biogenesis effectively eliminated their capacity to extend lifespan and reduce pathological protein aggregates. Together, these compelling findings highlight the potential of DTCA and ETCA as promising therapeutic interventions for delaying aging and preventing age-related diseases.</div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"218 ","pages":"Article 111901"},"PeriodicalIF":5.3,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139431959","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