The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

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Lumican is Both a Novel Risk Factor and Potential Plasma Biomarker for Vascular Aging, Capable of Promoting VSMCs Senescence through Interacting with Integrin α2β1. Lumican 既是血管老化的新型危险因素,也是潜在的血浆生物标志物,它能通过与整合素 α2β1 相互作用促进血管内皮细胞衰老。
Mandi Luo, Dan Yan, Yi Huang, Tianyi Ji, Pengcheng Luo, Zhen Yang, Shangbang Gao, Le Zhang, Yiwu Zhou, Qing Shi, Yongping Bai, Tao Li, Lei Ruan, Cuntai Zhang
{"title":"Lumican is Both a Novel Risk Factor and Potential Plasma Biomarker for Vascular Aging, Capable of Promoting VSMCs Senescence through Interacting with Integrin α2β1.","authors":"Mandi Luo, Dan Yan, Yi Huang, Tianyi Ji, Pengcheng Luo, Zhen Yang, Shangbang Gao, Le Zhang, Yiwu Zhou, Qing Shi, Yongping Bai, Tao Li, Lei Ruan, Cuntai Zhang","doi":"10.1093/gerona/glae214","DOIUrl":"https://doi.org/10.1093/gerona/glae214","url":null,"abstract":"<p><p>Vascular aging, a common pathogenesis of senile chronic diseases, significantly increases morbidity and mortality in older adults; its intricate cellular and molecular mechanisms necessitate further investigation. Lumican (LUM) and integrin α2β1(ITGα2β1) are profibrotic extracellular matrix proteins and vital cell regulatory receptors, respectively. However, their roles in vascular aging remain unclear. This study sought to elucidate the connection between LUM and vascular aging as well as the biological mechanism of LUM/ITGα2β1 in this process. Using an enzyme-linked immunosorbent assay, we discovered that plasma LUM was elevated in vascular aging individuals and was positively correlated with brachial-ankle pulse wave velocity. Additionally, immunohistochemical and western blot analyses confirmed LUM upregulation in arteries of older adults and aged mice, as well as in senescent vascular smooth cells (VSMCs). Wild-type and LUM semiknockout (Lum-/+) mice, along with primary VSMCs extracted from these mice, were exposed to angiotensin II (Ang II) to induce stress-induced senescence model. LUM semiknockout mitigated Ang Ⅱ-induced arteriosclerosis, hypertension, vascular aging and remodeling in mice. Both in vitro and in vivo studies revealed that LUM deficiency suppressed p53, p21, collagen 1 and collagen 3 upregulation and synthetic phenotype formation in VSMCs stimulated by Ang Ⅱ. Treating VSMCs with a ITGα2β1 antagonist reversed the aforementioned changes triggered by LUM proteins. Briefly, LUM functions as a potential marker and risk factor for vascular aging and promotes pathological changes by affecting ITGα2β1 in VSMCs. This study introduces a novel molecular target for the early diagnosis and treatment of vascular aging and age-related vascular diseases.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging. 对比增强超声成像检测大鼠颈椎微血管随着正常衰老而发生的解剖和功能变化。
Jennifer N Harmon, Preeja Chandran, Abarajithan Chandrasekaran, Jeffrey E Hyde, Gustavo J Hernandez, May J Reed, Matthew F Bruce, Zin Z Khaing
{"title":"Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging.","authors":"Jennifer N Harmon, Preeja Chandran, Abarajithan Chandrasekaran, Jeffrey E Hyde, Gustavo J Hernandez, May J Reed, Matthew F Bruce, Zin Z Khaing","doi":"10.1093/gerona/glae215","DOIUrl":"10.1093/gerona/glae215","url":null,"abstract":"<p><p>Normal aging is associated with significant deleterious cerebrovascular changes; these have been implicated in disease pathogenesis and increased susceptibility to ischemic injury. While these changes are well documented in the brain, few studies have been conducted in the spinal cord. Here, we utilize specialized contrast-enhanced ultrasound (CEUS) imaging to investigate age-related changes in cervical spinal vascular anatomy and hemodynamics in male Fisher 344 rats, a common strain in aging research. Aged rats (24-26 mo., N=6) exhibited significant tortuosity in the anterior spinal artery and elevated vascular resistance compared to adults (4-6 mo., N=6; tortuosity index 2.20±0.15 vs 4.74±0.45, p<0.05). Baseline blood volume was lower in both larger vessels and the microcirculation in the aged cohort, specifically in white matter (4.44e14±1.37e13 vs 3.66e14±2.64e13 CEUS bolus AUC, p<0.05). To elucidate functional differences, animals were exposed to a hypoxia challenge; whereas adult rats exhibited significant functional hyperemia in both gray and white matter (GM: 1.13±0.10-fold change from normoxia, p<0.05; WM: 1.16±0.13, p<0.05), aged rats showed no response. Immunohistochemistry revealed reduced pericyte coverage and activated microglia behavior in aged rats, which may partially explain the lack of vascular response. This study provides the first in vivo description of age-related hemodynamic differences in the cervical spinal cord.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of OLR1 reduces SASP of nucleus pulposus cells by targeting autophagy-GATA4 axis. 抑制 OLR1 可通过靶向自噬-GATA4 轴减少髓核细胞的 SASP。
Jia-Wei Gao, Hang Shi, Fu-Ping Gao, Zhi-Min Zhou, Xin Peng, Rui Sun, V L F Cabral, Jian Li, Yun-Tao Wang, Xiao-Hu Wang, Xiao-Tao Wu
{"title":"Inhibition of OLR1 reduces SASP of nucleus pulposus cells by targeting autophagy-GATA4 axis.","authors":"Jia-Wei Gao, Hang Shi, Fu-Ping Gao, Zhi-Min Zhou, Xin Peng, Rui Sun, V L F Cabral, Jian Li, Yun-Tao Wang, Xiao-Hu Wang, Xiao-Tao Wu","doi":"10.1093/gerona/glae204","DOIUrl":"https://doi.org/10.1093/gerona/glae204","url":null,"abstract":"<p><p>Targeting cellular senescence and Senescence Associated Secretory Phenotype (SASP) through autophagy has emerged as a promising intervertebral disc (IVD) degeneration (IDD) treatment strategy in recent years. This study aimed to clarify the role and mechanism of autophagy in preventing IVD SASP. Methods involved in vitro experiments with nucleus pulposus (NP) tissues from normal and IDD patients, as well as an in vivo IDD animal model. GATA4's regulatory role in SASP was validated both in vitro and in vivo, while autophagy modulators were employed to assess their impact on GATA4 and SASP. Transcriptomic sequencing identified Oxidized low-density lipoprotein receptor 1 (OLR1) as a key regulator of autophagy and GATA4. A series of experiments manipulated OLR1 expression to investigate associated effects. Results demonstrated significantly increased senescent NP cells (NPCs) and compromised autophagy in IDD patients and animal models, with SASP closely linked to IDD progression. The aged disc milieu impeded autophagic GATA4 degradation, leading to elevated SASP expression in senescent NPCs. Restoring autophagy reversed senescence by degrading GATA4, hence disrupting the SASP cascade. Moreover, OLR1 was identified for its regulation of autophagy and GATA4 in senescent NPCs. Silencing OLR1 enhanced autophagic activity, suppressing GATA4-induced senescence and SASP expression in senescent NPCs. In conclusion, OLR1 was found to control autophagy-GATA4 and SASP, with targeted OLR1 inhibition holding promise in alleviating GATA4-induced senescence and SASP expression while delaying extracellular matrix degradation, offering a novel therapeutic approach for IDD management.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adverse Childhood Experiences and Later-Life Cognitive Aging: Persistent Methodological Challenges Limit the Evidence Base. 童年不良经历与晚年认知老化:持续的方法挑战限制了证据基础。
Lindsay C Kobayashi
{"title":"Adverse Childhood Experiences and Later-Life Cognitive Aging: Persistent Methodological Challenges Limit the Evidence Base.","authors":"Lindsay C Kobayashi","doi":"10.1093/gerona/glae138","DOIUrl":"10.1093/gerona/glae138","url":null,"abstract":"","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":"79 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11200183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452618","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
Somatic Factors Predict On-Road Driving Skills in Older Drivers and Drivers with Mild Cognitive Impairment. 躯体因素可预测老年驾驶员和轻度认知障碍驾驶员的道路驾驶技能。
Maximilian Flieger, Wolf Schäbitz, Daniel A Schlueter, Kim L Austerschmidt, Jessica Koenig, Thomas Beblo, Martin Driessen, Max Toepper
{"title":"Somatic Factors Predict On-Road Driving Skills in Older Drivers and Drivers with Mild Cognitive Impairment.","authors":"Maximilian Flieger, Wolf Schäbitz, Daniel A Schlueter, Kim L Austerschmidt, Jessica Koenig, Thomas Beblo, Martin Driessen, Max Toepper","doi":"10.1093/gerona/glae152","DOIUrl":"10.1093/gerona/glae152","url":null,"abstract":"<p><strong>Background: </strong>On-road driving skills can be impaired in older drivers and drivers with mild cognitive impairment (MCI) due to different driving-relevant deficits. Among these deficits, somatic factors have received little attention so far.</p><p><strong>Methods: </strong>In a prospective observational on-road driving study, we examined whether somatic factors can predict on-road driving skills in a mixed sample of healthy older drivers and drivers with MCI (n = 99) and whether the inclusion of age explains additional variance. Somatic factors included the number of prescribed drugs, visual acuity, peripheral visual field integrity, mobility of the cervical spine, and hearing impairment. A hierarchical regression analysis was used to predict on-road driving skills by adding the somatic factors in the first step and age in the second step.</p><p><strong>Results: </strong>Results revealed that the combination of somatic factors significantly predicted on-road driving skills (R2adjusted = 0.439). The inclusion of age led to a significant increase of explained variance (R2adjusted = 0.466).</p><p><strong>Conclusions: </strong>Our results suggest that somatic factors can accurately predict on-road driving skills in healthy older drivers and drivers with MCI. In addition, our results suggest that there is a significant but rather small effect of age beyond somatic changes.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DNA Methylation at C-Reactive Protein-Associated CpG Sites May Mediate the Pathway Between Educational Attainment and Cognition. CRP相关CpG位点的DNA甲基化可能介导教育成就与认知之间的途径
Meike Stoldt, Farah Ammous, Lisha Lin, Scott M Ratliff, Erin B Ware, Jessica D Faul, Wei Zhao, Sharon L R Kardia, Jennifer A Smith
{"title":"DNA Methylation at C-Reactive Protein-Associated CpG Sites May Mediate the Pathway Between Educational Attainment and Cognition.","authors":"Meike Stoldt, Farah Ammous, Lisha Lin, Scott M Ratliff, Erin B Ware, Jessica D Faul, Wei Zhao, Sharon L R Kardia, Jennifer A Smith","doi":"10.1093/gerona/glae159","DOIUrl":"10.1093/gerona/glae159","url":null,"abstract":"<p><p>Growing evidence has linked inflammatory processes to cognitive decline and dementia. This work examines whether an epigenetic marker of C-reactive protein (CRP), a common clinical inflammatory biomarker, may mediate the relationship between educational attainment and cognition. We first evaluated whether 53 previously reported CRP-associated DNA methylation sites (CpGs) are associated with CRP, both individually and aggregated into a methylation risk score (MRSCRP), in 3 298 participants from the Health and Retirement Study (HRS, mean age = 69.7 years). Forty-nine CpGs (92%) were associated with the natural logarithm of CRP in HRS after adjusting for age, sex, smoking, BMI, genetic ancestry, and white blood cell counts (p < .05), and each standard deviation increase in MRSCRP was associated with a 0.38 unit increase in lnCRP (p = 4.02E-99). In cross-sectional analysis, for each standard deviation increase in MRSCRP, total memory score and total cognitive score decreased, on average, by 0.28 words and 0.43 items, respectively (p < .001). Further, MRSCRP mediated 6.9% of the relationship between high school education and total memory score in a model adjusting for age, sex, and genetic ancestry (p < .05); this was attenuated to 2.4% with additional adjustment for marital status, APOE ε4 status, health behaviors, and comorbidities (p < .05). Thus, CRP-associated methylation may partially mediate the relationship between education and cognition at older ages. Further research is warranted to determine whether DNA methylation at these sites may improve current prediction models for cognitive impairment in older adults.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422341","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 Linkage and Association Analyses Identify DLG Associated Protein-1 as a Novel Positional and Biological Candidate Gene for Muscle Strength: The Long Life Family Study. 全基因组关联和关联分析发现 DLG 相关蛋白-1 是肌肉力量的一个新的位置和生物学候选基因:长寿家族研究
Adam J Santanasto, Sandeep Acharya, Mary K Wojczynski, Ryan K Cvejkus, Shiow Lin, Michael R Brent, Jason A Anema, Lihua Wang, Bharat Thyagarajan, Kaare Christensen, E Warwick Daw, Joseph M Zmuda
{"title":"Whole Genome Linkage and Association Analyses Identify DLG Associated Protein-1 as a Novel Positional and Biological Candidate Gene for Muscle Strength: The Long Life Family Study.","authors":"Adam J Santanasto, Sandeep Acharya, Mary K Wojczynski, Ryan K Cvejkus, Shiow Lin, Michael R Brent, Jason A Anema, Lihua Wang, Bharat Thyagarajan, Kaare Christensen, E Warwick Daw, Joseph M Zmuda","doi":"10.1093/gerona/glae144","DOIUrl":"10.1093/gerona/glae144","url":null,"abstract":"<p><strong>Background: </strong>Grip strength is a robust indicator of overall health, is moderately heritable, and predicts longevity in older adults.</p><p><strong>Methods: </strong>Using genome-wide linkage analysis, we identified a novel locus on chromosome 18p (mega-basepair region: 3.4-4.0) linked to grip strength in 3 755 individuals from 582 families aged 64 ± 12 years (range 30-110 years; 55% women). There were 26 families that contributed to the linkage peak (cumulative logarithm of the odds [LOD] score = 10.94), with 6 families (119 individuals) accounting for most of the linkage signal (LOD = 6.4). In these 6 families, using whole genome sequencing data, we performed association analyses between the 7 312 single nucleotide (SNVs) and insertion deletion (INDELs) variants in the linkage region and grip strength. Models were adjusted for age, age2, sex, height, field center, and population substructure.</p><p><strong>Results: </strong>We found significant associations between genetic variants (8 SNVs and 4 INDELs, p < 5 × 10-5) in the Disks Large-associated Protein 1 (DLGAP1) gene and grip strength. Haplotypes constructed using these variants explained up to 98.1% of the LOD score. Finally, RNAseq data showed that these variants were significantly associated with the expression of nearby Myosin Light Chain 12A (MYL12A), Structural Maintenance of Chromosomes Flexible Hinge Domain Containing 1 (SMCHD1), Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3) genes (p < .0004).</p><p><strong>Conclusions: </strong>The DLGAP1 gene plays an important role in the postsynaptic density of neurons; thus, it is both a novel positional and biological candidate gene for follow-up studies aimed at uncovering genetic determinants of muscle strength.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162703","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
Links of Previous Incarceration With Geriatric Syndromes and Chronic Health Conditions Among Older Adults in the United States. 美国老年人曾被监禁与老年综合症和慢性健康状况之间的联系。
Alexander Testa, Dylan B Jackson, Meghan Novisky, Christopher Kaufmann, Carmen Gutierrez, Jack Tsai, Adam P Spira, Roland J Thorpe
{"title":"Links of Previous Incarceration With Geriatric Syndromes and Chronic Health Conditions Among Older Adults in the United States.","authors":"Alexander Testa, Dylan B Jackson, Meghan Novisky, Christopher Kaufmann, Carmen Gutierrez, Jack Tsai, Adam P Spira, Roland J Thorpe","doi":"10.1093/gerona/glae084","DOIUrl":"10.1093/gerona/glae084","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the association between previous incarceration and various geriatric and chronic health conditions among adults 50 and older in the United States.</p><p><strong>Methods: </strong>Data came from the National Longitudinal Study of Adolescent to Adult Health-Parent Study (AHPS) collected in 2015-2017, including 2 007 individuals who participated in the parent study (Parent Sample) and 976 individuals who participated in the spouse/partner study (Spouse/Partner Sample). Multiple logistic regression was used to investigate the relationship between previous incarceration and geriatric syndromes (dementia, difficulty walking, difficulty seeing, difficulty with activities of daily living) and chronic health conditions (self-reported poor/fair health, diagnosis of cancer, hypertension, diabetes, heart disease, stroke, chronic lung disease, depression, and alcohol use [4 or more drinks per week]).</p><p><strong>Results: </strong>In adjusted analyses, respondents with previous incarceration in the AHPS had significantly higher odds of reporting difficulty walking, activities of daily living difficulty, cancer diagnosis, depression diagnosis, and chronic lung disease (adjusted odds ratios [aORs] = 2.21-2.95). Respondents in the AHPS spouse/partner study reported higher odds of difficulty seeing, cancer, depression, chronic lung disease, and heavy alcohol use (aORs = 1.02-2.15).</p><p><strong>Conclusions: </strong>Previous incarceration may have an adverse impact on healthy aging. Findings highlight the importance of addressing the enduring health impacts of incarceration, particularly as individual transition into older adulthood.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190536","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
Consideration of T-Cell Profile in the Examination of Statin Efficacy in Inflammatory Diseases, Neurodegeneration, and Neurocognitive Performance. 在研究他汀类药物对炎症性疾病、神经变性和神经认知能力的疗效时考虑 T 细胞特征。
Matthew A Hintermayer, Daniel Mendelson, Jae Hyun Byun
{"title":"Consideration of T-Cell Profile in the Examination of Statin Efficacy in Inflammatory Diseases, Neurodegeneration, and Neurocognitive Performance.","authors":"Matthew A Hintermayer, Daniel Mendelson, Jae Hyun Byun","doi":"10.1093/gerona/glae156","DOIUrl":"10.1093/gerona/glae156","url":null,"abstract":"<p><p>Statins are a cornerstone in the medical management of cardiovascular disease, yet their efficacy varies greatly between individuals. In this commentary, we outline the evidence for the role of CD4+CD28null T-cell expansion as a critical moderator of the effects of statins in preventing cardiovascular events via the reduction of pathological inflammation. Given this relationship, we argue that T-cell profiles should be considered as a patient characteristic in clinical and preclinical studies examining statin efficacy in other age- and inflammation-related pathologies. We discuss the implications this may have for studies of statin use in numerous disease processes-notably, dementia and neurocognitive dysfunction-and the potential for T-cell profiles to be used as a prognosticator for statin efficacy in rheumatoid arthritis, Alzheimer's disease, and multiple sclerosis.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536315","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
Is the Risk of Alzheimer's Disease and Related Dementias Among U.S. Veterans Influenced by the Intersectionality of Housing Status, HIV/AIDS, Hepatitis C, and Psychiatric Disorders? 美国退伍军人罹患阿尔茨海默病和相关痴呆症的风险是否受到住房状况、艾滋病毒/艾滋病、丙型肝炎和精神疾病的交叉影响?
Hind A Beydoun, Dorota Szymkowiak, Rebecca Kinney, May A Beydoun, Alan B Zonderman, Jack Tsai
{"title":"Is the Risk of Alzheimer's Disease and Related Dementias Among U.S. Veterans Influenced by the Intersectionality of Housing Status, HIV/AIDS, Hepatitis C, and Psychiatric Disorders?","authors":"Hind A Beydoun, Dorota Szymkowiak, Rebecca Kinney, May A Beydoun, Alan B Zonderman, Jack Tsai","doi":"10.1093/gerona/glae153","DOIUrl":"10.1093/gerona/glae153","url":null,"abstract":"<p><strong>Background: </strong>Homelessness and housing instability disproportionately affect U.S. veterans with psychiatric disorders, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), hepatitis C, and Alzheimer's disease and related disorders (ADRD). We examined housing status and/or HIV/AIDS in relation to ADRD risk and evaluated hepatitis C, substance use, and mental health disorders as mediators and/or moderators of hypothesized relationships, among U.S. veterans ≥50 years of age seeking Department of Veterans Affairs (VA) healthcare services.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using linked VA Homeless Operations Management and Evaluation System and Corporate Data Warehouse databases (2017-2023) on 3 275 098 eligible veterans yielding 133 388 ADRD cases over 5 years of follow-up. Multivariable regression and causal mediation analyses were performed, controlling for demographic and clinical characteristics.</p><p><strong>Results: </strong>Taking stably housed veterans without HIV/AIDS as referent, ADRD risk was higher among veterans with homelessness/housing instability alone (adjusted hazard ratio [aHR] = 1.67, 95% confidence interval [CI]: 1.63,1.72), lower among veterans with HIV/AIDS alone (aHR = 0.65, 95% CI: 0.58,0.73), but similar to veterans with homelessness/housing instability and HIV/AIDS (aHR = 1.01, 95% CI: 0.79,1.29). In adjusted models, hepatitis C and psychiatric disorders were positively related to homelessness/housing instability and ADRD risk, but negatively related to HIV/AIDS. Statistically significant mediation and/or moderation of hepatitis C and psychiatric disorders were observed, although <10% of total effects were explained by these characteristics, controlling for confounders.</p><p><strong>Conclusions: </strong>Among older veterans, ADRD diagnoses over 5 years were less among those with HIV/AIDS, but more among those with homelessness/housing instability, and these relationships were partly explained by hepatitis C and psychiatric disorders.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312646","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
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