Aging-Us最新文献

{"title":"Cysteinyl leukotriene receptor 1 modulates retinal immune cells, vascularity and proteolytic activity in aged mice.","authors":"Andreas Koller, Julia Preishuber-Pflügl, Daniela Mayr, Susanne Maria Brunner, Anja-Maria Ladek, Christian Runge, Ludwig Aigner, Herbert Anton Reitsamer, Andrea Trost","doi":"10.18632/aging.206193","DOIUrl":"10.18632/aging.206193","url":null,"abstract":"<p><p>Cysteinyl leukotrienes (CysLTs) modulate the immune response, the microvasculature, cell stress and the endosomal-lysosomal system, and are involved in cellular aging. Interestingly, CysLT receptor 1 (Cysltr1) is highly expressed in the retina, a tissue that is strongly affected by the aging process. Thus, we performed an introductory examination to determine a potential importance of Cysltr1 for cells in the neurovascular unit using qPCR and immunofluorescence analysis, and on proteolytic activity in the retinas of aged mice. Aged mice (~84 weeks) were treated orally with vehicle or 10 mg/kg montelukast (MTK), a specific Cysltr1 inhibitor, for 8 weeks, 5x/week. The retinas of young mice (~11 weeks) served as controls. Compared with young control mice, aged mice exhibited increased numbers of microglia and a reduced retinal capillary diameter, but these age-dependent changes were abrogated by MTK treatment. Retinal protein levels of the ubiquitin binding protein sequestosome-1 were amplified by aging, but were reduced by MTK treatment. Interestingly, retinal proteasome activity was decreased in aged mice, whereas Cysltr1 inhibition increased this activity. The reduction in immune cells caused by Cysltr1 suppression may dampen neuroinflammation, a known promoter of tissue aging. Additionally, an increase in capillary diameter after Cysltr1 inhibition could have a beneficial effect on blood flow in aged individuals. Furthermore, the increase in proteolytic activity upon Cysltr1 inhibition could prevent the accumulation of toxic deposits, which is a hallmark of aged tissue. Overall, Cysltr1 is a promising target for modulating the impact of aging on retinal tissue.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"308-328"},"PeriodicalIF":3.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076583","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":"Correction for: The association between KLF4 as a tumor suppressor and the prognosis of hepatocellular carcinoma after curative resection.","authors":"Min Xue, Chenhao Zhou, Yan Zheng, Ziping Zhang, Shun Wang, Yan Fu, Manar Atyah, Xiaolong Xue, Le Zhu, Qiongzhu Dong, Huliang Jia, Ning Ren, Ruolei Hu","doi":"10.18632/aging.206197","DOIUrl":"10.18632/aging.206197","url":null,"abstract":"","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 1","pages":"276-277"},"PeriodicalIF":3.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071256","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":"Retraction of: LINC00265 targets miR-382-5p to regulate SAT1, VAV3 and angiogenesis in osteosarcoma.","authors":"Ying Xiao, Chunling Li, Hongyue Wang, Yijun Liu","doi":"10.18632/aging.206195","DOIUrl":"10.18632/aging.206195","url":null,"abstract":"","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 1","pages":"278-279"},"PeriodicalIF":3.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071258","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":"Diet, lifestyle and telomere length: using Copula Graphical Models on NHANES data.","authors":"Angelo M Tedaldi, Pariya Behrouzi, Pol Grootswagers","doi":"10.18632/aging.206194","DOIUrl":"10.18632/aging.206194","url":null,"abstract":"<p><p>Telomere length has been related to human health and ageing in multiple studies. However, these studies have analyzed a small set of variables, according to pre-formulated hypotheses. We used data from NHANES 1999-2002 to perform a preregistered cross-sectional analysis. From these four years we selected the participants with available leukocyte telomere length measure and with plausible daily energy intake, leading to a total study population of 7096 participants. Then, we divided the participants in three groups according to age: Young 20-39 (<i>n</i> = 2623), Middle 40-59 (<i>n</i> = 2210), Old 60-84 (<i>n</i> = 2263). On each group we performed Copula Graphical Modelling (CGM) to capture the links between the variables of interest, and we conducted certainty and sensitivity analyses to understand the robustness of the results. Blood levels of C-reactive protein and γ-tocopherol, and intake of caffeine and fibers are inversely related to telomere length across the age strata. Sex, race, smoking, physical activity and indicators of socioeconomic status have almost no direct connection with telomeres; however, they are directly linked to C-reactive protein, which in turn is connected to leukocyte telomere length. C-reactive protein is therefore a possible central mediator of the effect of these factors on telomeres.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"329-356"},"PeriodicalIF":3.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069657","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":"Age-invariant genes: multi-tissue identification and characterization of murine reference genes.","authors":"John T González, Kyra Thrush-Evensen, Margarita Meer, Morgan E Levine, Albert T Higgins-Chen","doi":"10.18632/aging.206192","DOIUrl":"10.18632/aging.206192","url":null,"abstract":"<p><p>Studies of the aging transcriptome focus on genes that change with age. But what can we learn from age-invariant genes-those that remain unchanged throughout the aging process? These genes also have a practical application: they can serve as reference genes in expression studies. Reference genes have mostly been identified and validated in young organisms, and no systematic investigation has been done across the lifespan. Here, we build upon a common pipeline for identifying reference genes in RNA-seq datasets to identify age-invariant genes across seventeen C57BL/6 mouse tissues (brain, lung, bone marrow, muscle, white blood cells, heart, small intestine, kidney, liver, pancreas, skin, brown, gonadal, marrow, and subcutaneous adipose tissue) spanning 1 to 21+ months of age. We identify 9 pan-tissue age-invariant genes, and many tissue-specific age-invariant genes. These genes are stable across the lifespan and are validated in independent bulk RNA-seq datasets and RT-qPCR. Age-invariant genes have shorter transcripts and are enriched for CpG islands. Interestingly, pathway enrichment analysis for age-invariant genes identifies an overrepresentation of molecular functions associated with some, but not all, hallmarks of aging. Thus, even though hallmarks of aging typically involve change, select genes associated with these hallmarks resist age-related change. Finally, our analysis provides a list of murine tissues where classical reference genes are appropriate for application in aging studies. However, no classical reference gene is appropriate across all aging tissues. Instead, we provide novel tissue-specific and pan-tissue reference genes for assays utilizing gene normalization (RT-qPCR) that can be applied to mice across the lifespan.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"170-202"},"PeriodicalIF":3.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054346","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":"Oct4, Sox2, Klf4, c-My (OSKM) gene therapy in the hypothalamus prolongs fertility and ovulation in female rats.","authors":"Maria D Gallardo, Mauricio Girard, Enrique L Portiansky, Rodolfo G Goya","doi":"10.18632/aging.206191","DOIUrl":"10.18632/aging.206191","url":null,"abstract":"<p><p>In middle-aged (MA) female rats, we have demonstrated that intrahypothalamic gene therapy for insulin-like growth factor-I (IGF-I) extends the regular cyclicity of the animals beyond 10 months (the age at which MA rats stop ovulating). Here, we implemented long-term OSKM gene therapy in the hypothalamus of young female rats. The main goal was to extend fertility in the treated animals. We constructed an adenovector that harbors the GFP gene as well as 4 Yamanaka genes. An adenovector that only carries the gene for GFP or DsRed was used as control. At 4 months of age 12 female rats received an intrahypothalamic injection of our OSKM vector (treated rats); 12 control rats received a vector expressing a marker gene (control rats). At 9.3 months of age control and treated rats were mated with young males. A group of 12 young intact female rats was also mated. The rate of pregnancy recorded was 83%, 8.3 and 25% for young, MA control and MA treated animals, respectively. Pup body weight (BW) at weaning was significantly higher in the MA OSKM rats than in MA controls. At the age of estropause (10 months), OSKM treated females still showed regular estrous cycles. The particular significance of the present results is that, for the first time, it is shown that long-term OSKM gene therapy in the hypothalamus is able to extend the functionality of such a complex system as the hypothalamo-pituitary-ovarian axis.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"161-169"},"PeriodicalIF":3.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048922","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":"EpiAge: a next-generation sequencing-based <i>ELOVL2</i> epigenetic clock for biological age assessment in saliva and blood across health and disease.","authors":"David Cheishvili, Sonia Do Carmo, Filippo Caraci, Margherita Grasso, A Claudio Cuello, Moshe Szyf","doi":"10.18632/aging.206188","DOIUrl":"10.18632/aging.206188","url":null,"abstract":"<p><p>This study introduces EpiAgePublic, a new method to estimate biological age using only three specific sites on the gene <i>ELOVL2,</i> known for its connection to aging. Unlike traditional methods that require complex and extensive data, our model uses a simpler approach that is well-suited for next-generation sequencing technology, which is a more advanced method of analyzing DNA methylation. This new model overcomes some of the common challenges found in older methods, such as errors due to sample quality and processing variations. We tested EpiAgePublic with a large and varied group of over 4,600 people to ensure its accuracy. It performed on par with, and sometimes better than, more complicated models that use much more data for age estimation. We examined its effectiveness in understanding how factors like HIV infection and stress affect aging, confirming its usefulness in real-world clinical settings. Our results prove that our simple yet effective model, EpiAgePublic, can capture the subtle signs of aging with high accuracy. We also used this model in a study involving patients with Alzheimer's Disease, demonstrating the practical benefits of next-generation sequencing in making precise age-related assessments. This study lays the groundwork for future research on aging mechanisms and assessing how different interventions might impact the aging process using this clock.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"131-160"},"PeriodicalIF":3.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034781","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":"Deep learning and generative artificial intelligence in aging research and healthy longevity medicine.","authors":"Dominika Wilczok","doi":"10.18632/aging.206190","DOIUrl":"10.18632/aging.206190","url":null,"abstract":"<p><p>With the global population aging at an unprecedented rate, there is a need to extend healthy productive life span. This review examines how Deep Learning (DL) and Generative Artificial Intelligence (GenAI) are used in biomarker discovery, deep aging clock development, geroprotector identification and generation of dual-purpose therapeutics targeting aging and disease. The paper explores the emergence of multimodal, multitasking research systems highlighting promising future directions for GenAI in human and animal aging research, as well as clinical application in healthy longevity medicine.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"251-275"},"PeriodicalIF":3.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016226","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":"Association between physical activity practice and sleep quality of older people in social isolation during the COVID-19 pandemic and Health Guidelines and future studies for the post-COVID period: a systematic review.","authors":"Alexandro Andrade, Ana Cecília Rosatelli de Freitas Bastos, Anderson D'Oliveira, Guilherme Torres Vilarino","doi":"10.18632/aging.206180","DOIUrl":"10.18632/aging.206180","url":null,"abstract":"<p><strong>Purpose: </strong>Physical activity (PA) is considered an alternative to mitigate the negative impacts of the COVID-19 pandemic on the sleep of older adults. The objective was to verify the association between physical activity and the sleep quality of older people in social isolation during the COVID-19 pandemic, to analyze the Health Guidelines, and suggest future studies for the post-COVID period.</p><p><strong>Methods: </strong>This systematic review followed PRISMA recommendations, and the protocol was registered in PROSPERO (CRD 42023406471). The search for articles occurred in April 2024 in the databases PubMed, Web of Science, SCOPUS, and gray literature. Data were extracted and checked in a Microsoft Excel^® spreadsheet. The quality assessment was performed using tools from the National Institutes of Health.</p><p><strong>Results: </strong>In total, 1582 studies were found in the databases, of which nine were included in the analyses. Four studies reported a negative association of reduced levels of PA during the pandemic with sleep quality, while one study showed a positive association of PA with sleep quality. Four studies demonstrated no association.</p><p><strong>Conclusions: </strong>PA was associated with the sleep quality of older adults during the COVID-19 pandemic and reduced levels of PA during this period demonstrated a negative association with sleep quality. Practice of PA is recommended for this post-COVID scenario, as a measure to reduce social isolation and its negative effects and improve the quality of sleep in older adults.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"51-66"},"PeriodicalIF":3.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016217","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 comparison of serum bone-turnover markers in different stage of chronic kidney disease and the associated impact of intradialytic cycling in patients with end-stage renal disease.","authors":"Yi-Chou Hou, Chia-Ter Chao, Li-Jane Shih, Kuo-Wang Tsai, Shyh-Min Lin, Ruei-Ming Chen, Kuo-Cheng Lu","doi":"10.18632/aging.206177","DOIUrl":"10.18632/aging.206177","url":null,"abstract":"<p><strong>Introduction: </strong>Bone turnover markers reflected the bone remodeling process and bone health in clinical studies. Studies on variation of bone remodeling markers in different stage CKD were scant, and this study investigated the role of bedside intradialytic cycling in altering concentrations of bone-remodeling markers in patients with end-stage renal disease (ESRD).</p><p><strong>Materials and methods: </strong>Participants were segmented into four groups: a group with eGFR >60 ml/min/1.73 m², a chronic kidney disease group with eGFR 15-60 mL/min/1.73 m²), an ESRD group with an exercise intervention, and an ESRD group with standard care. Comparison of bone turnover markers was performed among groups. The intervention consisting of 12 weeks of intradialytic cycling was performed during dialysis. The variation of bone-remodeling markers was compared between the ESRD with exercise along with the ESRD with standard care after 12-week monitoring.</p><p><strong>Results: </strong>Bone-formative marker levels (bone-specific alkaline phosphatase and procollagen type 1 amino-terminal propeptide, P1NP) were higher in ESRD patients than in non-ESRD patients and were correlated with indoxyl sulfate and intact parathyroid hormone concentrations (<i>p</i> < 0.05). Postexercise concentrations of tartrate-resistant acid phosphatase-5b (<i>p</i> = 0.003) and N-terminal telopeptide-1 (<i>p</i> = 0.001) had increased in the ESRD patients after 12 weeks of bedside cycling. Bone-formative marker concentration was not altered in the exercise group after cycling.</p><p><strong>Conclusion: </strong>Bone-formative marker concentrations increased with the severity of chronic kidney disease. Bone formative markers concentration increased along with CKD severity. We demonstrated the bone resorptive markers tartrate-resistant acid phosphatase-5b and N-terminal telopeptide-1 increased after intradialytic cycling in ESRD patients.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"217-231"},"PeriodicalIF":3.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985429","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}