npj aging最新文献_第2页

Emerging insights in senescence: pathways from preclinical models to therapeutic innovations. 衰老的新见解：从临床前模型到治疗创新的途径。

IF 4.1

npj aging Pub Date : 2024-11-22 DOI: 10.1038/s41514-024-00181-1

Luke Mansfield, Valentina Ramponi, Kavya Gupta, Thomas Stevenson, Abraham Binoy Mathew, Agian Jeffilano Barinda, Florencia Herbstein, Samir Morsli

{"title":"Emerging insights in senescence: pathways from preclinical models to therapeutic innovations.","authors":"Luke Mansfield, Valentina Ramponi, Kavya Gupta, Thomas Stevenson, Abraham Binoy Mathew, Agian Jeffilano Barinda, Florencia Herbstein, Samir Morsli","doi":"10.1038/s41514-024-00181-1","DOIUrl":"10.1038/s41514-024-00181-1","url":null,"abstract":"Senescence is a crucial hallmark of ageing and a significant contributor to the pathology of age-related disorders. As committee members of the young International Cell Senescence Association (yICSA), we aim to synthesise recent advancements in the identification, characterisation, and therapeutic targeting of senescence for clinical translation. We explore novel molecular techniques that have enhanced our understanding of senescent cell heterogeneity and their roles in tissue regeneration and pathology. Additionally, we delve into in vivo models of senescence, both non-mammalian and mammalian, to highlight tools available for advancing the contextual understanding of in vivo senescence. Furthermore, we discuss innovative diagnostic tools and senotherapeutic approaches, emphasising their potential for clinical application. Future directions of senescence research are explored, underscoring the need for precise, context-specific senescence classification and the integration of advanced technologies such as machine learning, long-read sequencing, and multifunctional senoprobes and senolytics. The dual role of senescence in promoting tissue homoeostasis and contributing to chronic diseases highlights the complexity of targeting these cells for improved clinical outcomes.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"53"},"PeriodicalIF":4.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Whole-genome sequencing to identify rare variants in East Asian patients with dementia with Lewy bodies. 通过全基因组测序鉴定东亚路易体痴呆症患者的罕见变异。

IF 4.1

npj aging Pub Date : 2024-11-21 DOI: 10.1038/s41514-024-00180-2

Tetsuaki Kimura, Kosuke Fujita, Takashi Sakurai, Shumpei Niida, Kouichi Ozaki, Daichi Shigemizu

{"title":"Whole-genome sequencing to identify rare variants in East Asian patients with dementia with Lewy bodies.","authors":"Tetsuaki Kimura, Kosuke Fujita, Takashi Sakurai, Shumpei Niida, Kouichi Ozaki, Daichi Shigemizu","doi":"10.1038/s41514-024-00180-2","DOIUrl":"10.1038/s41514-024-00180-2","url":null,"abstract":"Dementia with Lewy bodies (DLB) is the second most common form of age-related dementia, following Alzheimer's disease (AD). DLB is associated with a worse prognosis than AD and is characterized by a more rapid progression of cognitive impairment and a poorer quality of life. In addition, the pathogenesis of DLB is less understood than that of AD, and only three genes-SNCA (α-synuclein), APOE (apolipoprotein E), and GBA1 (glucosylceramidase beta 1)-have been convincingly demonstrated to be associated with DLB. In this study, we utilized whole-genome sequencing data from 1744 Japanese individuals, comprising 45 DLB patients and 1699 cognitively normal older adults, aiming to identify new genes associated with DLB. Our genome-wide association studies of genes with potentially deleterious mutations identified the CDH23 gene as being associated with DLB, reaching a Bonferroni-corrected significance (P = 7.43 × 10-4). The gene contained three ethnicity-specific heterozygous missense variants (rs181275139, rs563688802, and rs137937502). CDH23 has been linked to deafness syndromes, and DLB patients carrying these mutations displayed symptoms of subjective hearing loss, suggesting a potential association between DLB onset and auditory impairment. Additionally, we explored human leukocyte antigen (HLA) genotypes associated with DLB but found no significant associations. This result suggests that the pathology of DLB differs from that of Parkinson's disease, which has been reported to have an association with HLA. Although a limitation of this study is the lack of replication of our findings, which require further validation in independent cohorts, our study enhances the understanding of the etiology of DLB in the Japanese population and provides new insights into the underlying mechanisms of its pathogenesis.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"52"},"PeriodicalIF":4.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic variants associated with longevity in long-living Indians. 长寿印第安人中与长寿有关的基因变异。

IF 4.1

npj aging Pub Date : 2024-11-20 DOI: 10.1038/s41514-024-00179-9

Sandhya Kiran Pemmasani, Shakthiraju R G, Suraj V, Raunaq Bhattacharyya, Chetan Patel, Anil Kumar Gupta, Anuradha Acharya

{"title":"Genetic variants associated with longevity in long-living Indians.","authors":"Sandhya Kiran Pemmasani, Shakthiraju R G, Suraj V, Raunaq Bhattacharyya, Chetan Patel, Anil Kumar Gupta, Anuradha Acharya","doi":"10.1038/s41514-024-00179-9","DOIUrl":"10.1038/s41514-024-00179-9","url":null,"abstract":"Genetic factors play a significant role in determining an individual's longevity. The present study was aimed at identifying genetic variants associated with longevity in Indian population. Long living individuals (LLIs), aged 85+, were compared with younger controls, aged 18-49 years, using data from GenomegaDB, a genetic database of Indians living in India. An in-house developed custom chip, having variants associated with various cancers, cardiovascular, neurological, gastro-intestinal, metabolic and auto-immune disorders, was used to generate genotype data. Logistic regression analysis with sex and top three genetic principal components as covariates resulted in 9 variants to be significantly associated with longevity at a p-value threshold of 5 × 10-4. Alleles associated with slower heart rate (rs365990, MYH6), decreased risk of osteoporosis and short body height (rs2982570, ESR1), decreased risk of schizophrenia (rs1339227, RIMS1-KCNQ5) and decreased risk of anxiety and neuroticism (rs391957, HSPA5) were found to have higher frequency in LLIs. Alleles associated with increased risk of atrial fibrillation (rs3903239, GORAB-PRRX1) and biliary disorders (rs2002042, ABCC2) were found to have lower frequency. The G allele of rs2802292 from FOXO3A gene, associated with longevity in Japanese, German and French centenarians, was also found to be significant in this population (P = 0.032). Pathway enrichment analysis revealed that the genes involved in oxidative stress, apoptosis, DNA damage repair, glucose metabolism and energy metabolism were significantly involved in affecting the longevity. Results of our study demonstrate the genetic basis of healthy aging and longevity in the population.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"51"},"PeriodicalIF":4.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mapping computational cognitive profiles of aging to dissociable brain and sociodemographic factors. 将老龄化的计算认知特征与可分离的大脑和社会人口因素进行映射。

IF 4.1

npj aging Pub Date : 2024-10-31 DOI: 10.1038/s41514-024-00171-3

Aleya A Marzuki, Kean Yung Wong, Jee Kei Chan, Sze Yie Na, Arjun Thanaraju, Paveen Phon-Amnuaisuk, Samira Vafa, Jie Yap, Wei Gene Lim, Wei Zern Yip, Annette Shamala Arokiaraj, Dexter Shee, Louisa Gee Ling Lee, Yook Chin Chia, Michael Jenkins, Alexandre Schaefer

{"title":"Mapping computational cognitive profiles of aging to dissociable brain and sociodemographic factors.","authors":"Aleya A Marzuki, Kean Yung Wong, Jee Kei Chan, Sze Yie Na, Arjun Thanaraju, Paveen Phon-Amnuaisuk, Samira Vafa, Jie Yap, Wei Gene Lim, Wei Zern Yip, Annette Shamala Arokiaraj, Dexter Shee, Louisa Gee Ling Lee, Yook Chin Chia, Michael Jenkins, Alexandre Schaefer","doi":"10.1038/s41514-024-00171-3","DOIUrl":"10.1038/s41514-024-00171-3","url":null,"abstract":"Aging is associated with declines in cognition and brain structural integrity. However, there is equivocality over (1) the specificity of affected domains in different people, (2) the location of associated patterns of brain structural deterioration, and (3) the sociodemographic factors contributing to 'unhealthy' cognition. We aimed to identify cognitive profiles displayed by older adults and determine brain and sociodemographic features potentially shaping these profiles. A sample of Southeast-Asian older adults (N = 386) participated in a multi-session study comprising cognitive testing, neuroimaging, and a structured interview. We used computational models to extract latent mechanisms underlying cognitive flexibility and response inhibition. Data-driven methods were used to construct cognitive profiles based on standard performance measures and model parameters. We also investigated grey matter volume and machine-learning derived 'brain-ages'. A profile associated with poor set-shifting and rigid focusing was associated with widespread grey matter reduction in cognitive control regions. A slow responding profile was associated with advanced brain-age. Both profiles were correlated with poor socioeconomic standing and cognitive reserve. We found that the impact of sociodemographic factors on cognitive profiles was partially mediated by total grey and white matter, and dorsolateral prefrontal and cerebellar volumes. This study furthers understanding of how distinct aging profiles of cognitive impairment uniquely correspond to specific vs. global brain deterioration and the significance of socioeconomic factors in informing cognitive performance in older age.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"50"},"PeriodicalIF":4.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leonard Hayflick (1928-2024) - obituary. 伦纳德-海弗里克（1928-2024 年）--讣告。

IF 4.1

npj aging Pub Date : 2024-10-31 DOI: 10.1038/s41514-024-00174-0

Manuel Serrano

引用次数: 0

The role of the dynamic epigenetic landscape in senescence: orchestrating SASP expression. 动态表观遗传景观在衰老中的作用：协调 SASP 的表达。

IF 4.1

npj aging Pub Date : 2024-10-24 DOI: 10.1038/s41514-024-00172-2

Nirmalya Dasgupta, Rouven Arnold, Anais Equey, Armin Gandhi, Peter D Adams

引用次数: 0

Aging and senescent fates of oligodendrocyte precursor cells in the mouse brain. 小鼠大脑少突胶质前体细胞的衰老和衰老命运。

IF 4.1

npj aging Pub Date : 2024-10-22 DOI: 10.1038/s41514-024-00176-y

Paul T Gomez, Chase M Carver, Sonia L Rodriguez, Liguo Wang, Xu Zhang, Marissa J Schafer

引用次数: 0

Cell senescence in cardiometabolic diseases. 心脏代谢疾病中的细胞衰老。

IF 4.1

npj aging Pub Date : 2024-10-21 DOI: 10.1038/s41514-024-00170-4

Mandy O J Grootaert

引用次数: 0

p53 dependence of senescence markers p21v1 and p21v2 in aging and acute injury. 衰老和急性损伤中衰老标志物 p21v1 和 p21v2 的 p53 依赖性。

IF 4.1

npj aging Pub Date : 2024-10-14 DOI: 10.1038/s41514-024-00175-z

Parmita Kar, Ashok Sivasailam, Rupa Lavarti, Lun Cai, Muthusamy Thangaraju, Emma Nguyen, Bhavishya Mundluru, Raghavan Pillai Raju

引用次数: 0

The impact of blood pressure lowering agents on the risk of worsening frailty among patients with diabetes mellitus: a cohort study. 降压药对糖尿病患者衰弱恶化风险的影响：一项队列研究。

IF 4.1

npj aging Pub Date : 2024-10-07 DOI: 10.1038/s41514-024-00173-1

Jui Wang, Szu-Ying Lee, Chia-Ter Chao, Jenq-Wen Huang, Kuo-Liong Chien

{"title":"The impact of blood pressure lowering agents on the risk of worsening frailty among patients with diabetes mellitus: a cohort study.","authors":"Jui Wang, Szu-Ying Lee, Chia-Ter Chao, Jenq-Wen Huang, Kuo-Liong Chien","doi":"10.1038/s41514-024-00173-1","DOIUrl":"https://doi.org/10.1038/s41514-024-00173-1","url":null,"abstract":"Patients with diabetes mellitus (DM) are at risk of developing frailty, but studies rarely addressed risk factors for frailty worsening. We investigated whether blood pressure (BP)-lowering agents influenced such risk in these patients. Adults with type 2 DM were identified from National Taiwan University Hospital, with the primary outcome, the worsening of frailty by ≧1 score increase of FRAIL scale determined. We used the Cox proportional hazards analysis to derive the risk of worsening frailty associated with BP-lowering agents. Among 41,440 patients with DM, 27.4% developed worsening frailty after 4.09 years of follow-up. Cox regression revealed that diuretics (hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06-1.18) and α-blocker (HR 1.14, 95% CI 1.06-1.23) users had a significantly higher risk of worsening frailty than non-users, whereas the risk was lower among β-blocker users (HR 0.93, 95% CI 0.88-0.98). It would be therefore prudent to weigh the advantages and disadvantages of using specific BP-lowering agent classes.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"44"},"PeriodicalIF":4.1,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0