npj aging最新文献

{"title":"Decoding senescence of aging single cells at the nexus of biomaterials, microfluidics, and spatial omics.","authors":"Abhijeet Venkataraman, Ivan Kordic, JiaXun Li, Nicholas Zhang, Nivik Sanjay Bharadwaj, Zhou Fang, Sandip Das, Ahmet F Coskun","doi":"10.1038/s41514-024-00178-w","DOIUrl":"10.1038/s41514-024-00178-w","url":null,"abstract":"<p><p>Aging has profound effects on the body, most notably an increase in the prevalence of several diseases. An important aging hallmark is the presence of senescent cells that no longer multiply nor die off properly. Another characteristic is an altered immune system that fails to properly self-surveil. In this multi-player aging process, cellular senescence induces a change in the secretory phenotype, known as senescence-associated secretory phenotype (SASP), of many cells with the intention of recruiting immune cells to accelerate the clearance of these damaged senescent cells. However, the SASP phenotype results in inducing secondary senescence of nearby cells, resulting in those cells becoming senescent, and improper immune activation resulting in a state of chronic inflammation, called inflammaging, in many diseases. Senescence in immune cells, termed immunosenescence, results in further dysregulation of the immune system. An interdisciplinary approach is needed to physiologically assess aging changes of the immune system at the cellular and tissue level. Thus, the intersection of biomaterials, microfluidics, and spatial omics has great potential to collectively model aging and immunosenescence. Each of these approaches mimics unique aspects of the body undergoes as a part of aging. This perspective highlights the key aspects of how biomaterials provide non-cellular cues to cell aging, microfluidics recapitulate flow-induced and multi-cellular dynamics, and spatial omics analyses dissect the coordination of several biomarkers of senescence as a function of cell interactions in distinct tissue environments. An overview of how senescence and immune dysregulation play a role in organ aging, cancer, wound healing, Alzheimer's, and osteoporosis is included. To illuminate the societal impact of aging, an increasing trend in anti-senescence and anti-aging interventions, including pharmacological interventions, medical procedures, and lifestyle changes is discussed, including further context of senescence.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"57"},"PeriodicalIF":4.1,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735411","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}

{"title":"Association between gut microbiota and locomotive syndrome risk in healthy Japanese adults: a cross-sectional study.","authors":"Minami Nishiyama, Sho Nakamura, Taizo Matsuki, Hiroto Narimatsu","doi":"10.1038/s41514-024-00184-y","DOIUrl":"10.1038/s41514-024-00184-y","url":null,"abstract":"<p><p>This cross-sectional study examined the association between gut microbiota composition and locomotive syndrome in 568 healthy Japanese adults (36.8% male, median age 58.5 years) using data from the Kanagawa \"ME-BYO\" Prospective Cohort Study. Locomotive syndrome was assessed using the 5-question Geriatric Locomotive Function Scale (GLFS-5). Linear discriminant analysis effect size showed an enrichment of Actinobacteria and depletion of Firmicutes in GLFS-5 positive individuals. Classification tree analysis identified three terminal nodes as GLFS-5 positive, with one node involving Holdemania. Participants aged ≥70.0 and <78.0 years who did not consume probiotic foods and had ≥0.04% relative abundance of Holdemania were classified as at risk for locomotive syndrome. Our findings suggest a potential association between gut microbiota, particularly higher Holdemania abundance, and locomotive syndrome in older adults. This study provides insights into the complex relationship between gut microbiome composition and musculoskeletal health in aging populations. However, the cross-sectional design limits causal inference.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"55"},"PeriodicalIF":4.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718083","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}

{"title":"Predicting poor performance on cognitive tests among older adults using wearable device data and machine learning: a feasibility study.","authors":"Collin Sakal, Tingyou Li, Juan Li, Xinyue Li","doi":"10.1038/s41514-024-00177-x","DOIUrl":"10.1038/s41514-024-00177-x","url":null,"abstract":"<p><p>Timely implementation of interventions to slow cognitive decline among older adults requires accurate monitoring to detect changes in cognitive function. Factors known to be associated with cognition that can be gathered from accelerometers, user interfaces, and other sensors within wearable devices could be used to train machine learning models and develop wearable-based cognitive monitoring systems. Using data from over 2400 older adults in the National Health and Nutrition Examination Survey (NHANES) we developed prediction models to differentiate older adults with normal cognition from those with poor cognition based on outcomes from three cognitive tests measuring different domains of cognitive function. During repeated cross-validation CatBoost, XGBoost, and Random Forest models performed best when predicting poor cognition based on tests measuring processing speed, working memory, and attention (median AUCs ≥0.82) compared to immediate and delayed recall (median AUCs ≥0.72) and categorical verbal fluency (median AUC ≥ 0.68). Activity and sleep parameters were also more strongly associated with poor cognition based on tests assessing processing speed, working memory, and attention compared to other cognitive subdomains. Our work provides proof of concept that data collatable through wearable devices such as age, education, sleep parameters, activity summaries, and light exposure metrics could be used to differentiate between older adults with normal versus poor cognition. We further identified metrics that could be targets in future causal studies seeking to better understand how sleep and activity parameters influence cognitive function among older adults.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"56"},"PeriodicalIF":4.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718086","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}

{"title":"Aging modulates the impact of cognitive interference subtypes on dynamic connectivity across a distributed motor network.","authors":"Jake J Son, Yasra Arif, Hannah J Okelberry, Hallie J Johnson, Madelyn P Willett, Alex I Wiesman, Tony W Wilson","doi":"10.1038/s41514-024-00182-0","DOIUrl":"10.1038/s41514-024-00182-0","url":null,"abstract":"<p><p>Research has shown age-related declines in cognitive control in the context of interference, but these studies have focused on frontoparietal networks and less is known about impacts on motor response-related dynamics in the face of distractors. Thus, we examined whether healthy aging affected connectivity between attention networks and motor circuitry using a multisource interference task and magnetoencephalography in 72 healthy-aging participants (28-63 years-old). Our results indicated stronger beta connectivity with increasing age between bilateral primary motor (M1) and occipital cortices, as well as stronger gamma fronto-motor connectivity during flanker-type interference. Regarding Simon-type interference, stronger beta interactions were observed between left M1 and right temporal and right M1 and left parietal with increasing age. Finally, the superadditivity effect (flanker + Simon presented simultaneously) indicated weaker beta connectivity between right M1 and left premotor with increasing age. These findings suggest exhaustion of age-related compensatory adaptations in the fronto-parieto-motor network with greater interference.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"54"},"PeriodicalIF":4.1,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696287","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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.</p>","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}

{"title":"Leonard Hayflick (1928-2024) - obituary.","authors":"Manuel Serrano","doi":"10.1038/s41514-024-00174-0","DOIUrl":"10.1038/s41514-024-00174-0","url":null,"abstract":"","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"49"},"PeriodicalIF":4.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559897","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}

{"title":"The role of the dynamic epigenetic landscape in senescence: orchestrating SASP expression.","authors":"Nirmalya Dasgupta, Rouven Arnold, Anais Equey, Armin Gandhi, Peter D Adams","doi":"10.1038/s41514-024-00172-2","DOIUrl":"https://doi.org/10.1038/s41514-024-00172-2","url":null,"abstract":"<p><p>Senescence and epigenetic alterations stand out as two well-characterized hallmarks of aging. When cells become senescent, they cease proliferation and release inflammatory molecules collectively termed the Senescence-Associated Secretory Phenotype (SASP). Senescence and SASP are implicated in numerous age-related diseases. Senescent cell nuclei undergo epigenetic reprogramming, which intricately regulates SASP expression. This review outlines the current understanding of how senescent cells undergo epigenetic changes and how these alterations govern SASP expression.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"48"},"PeriodicalIF":4.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515562","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}