Jennifer N Harmon, Preeja Chandran, Abarajithan Chandrasekaran, Jeffrey E Hyde, Gustavo J Hernandez, May J Reed, Matthew F Bruce, Zin Z Khaing
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.
正常衰老与严重的脑血管有害变化有关;这些变化与疾病的发病机制和缺血性损伤的易感性增加有关。虽然这些变化在大脑中得到了很好的记录,但对脊髓的研究却很少。在这里,我们利用专门的对比增强超声(CEUS)成像技术来研究雄性费舍尔 344 大鼠(衰老研究中常见的品系)颈椎血管解剖结构和血液动力学中与年龄相关的变化。与成年大鼠(4-6 个月,N=6;迂曲指数为 2.20±0.15 vs 4.74±0.45, p)相比,老年大鼠(24-26 个月,N=6)的脊髓前动脉表现出明显的迂曲和血管阻力升高。
{"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}
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
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.
{"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}
{"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}
Maximilian Flieger, Wolf Schäbitz, Daniel A Schlueter, Kim L Austerschmidt, Jessica Koenig, Thomas Beblo, Martin Driessen, Max Toepper
Background: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
{"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}
Meike Stoldt, Farah Ammous, Lisha Lin, Scott M Ratliff, Erin B Ware, Jessica D Faul, Wei Zhao, Sharon L R Kardia, Jennifer A Smith
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.
越来越多的证据表明,炎症过程与认知能力下降和痴呆症有关。这项研究探讨了 C 反应蛋白(CRP)这一常见的临床炎症生物标志物的表观遗传标志物是否可能介导教育程度与认知能力之间的关系。我们首先在健康与退休研究(HRS,平均年龄=69.7 岁)的 3298 名参与者中评估了 53 个先前报告的与 CRP 相关的 DNA 甲基化位点(CpGs)是否与 CRP 相关,包括单独评估和汇总成一个甲基化风险评分(MRSCRP)。在对年龄、性别、吸烟、体重指数、遗传血统和白细胞计数进行调整后,49 个 CpGs(92%)与 HRS 中 CRP 的自然对数相关(p
{"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}
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
Background: Grip strength is a robust indicator of overall health, is moderately heritable, and predicts longevity in older adults.
Methods: 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.
Results: 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).
Conclusions: 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.
{"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}
Alexander Testa, Dylan B Jackson, Meghan Novisky, Christopher Kaufmann, Carmen Gutierrez, Jack Tsai, Adam P Spira, Roland J Thorpe
Background: This study investigated the association between previous incarceration and various geriatric and chronic health conditions among adults 50 and older in the United States.
Methods: 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]).
Results: 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).
Conclusions: 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.
{"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}
Matthew A Hintermayer, Daniel Mendelson, Jae Hyun Byun
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.
他汀类药物是治疗心血管疾病的基石,但其疗效却因人而异。在这篇评论中,我们概述了 CD4+CD28 空 T 细胞扩增作为他汀类药物通过减少病理炎症预防心血管事件效果的关键调节因子所起作用的证据。鉴于这种关系,我们认为,在对他汀类药物对其他年龄和炎症相关病症的疗效进行临床和临床前研究时,应将 T 细胞特征作为患者特征加以考虑。我们讨论了这可能对他汀类药物用于多种疾病过程(尤其是痴呆症和神经认知功能障碍)的研究产生的影响,以及 T 细胞特征作为他汀类药物对类风湿性关节炎、阿尔茨海默病和多发性硬化症疗效的预后指标的潜力。
{"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}
Hind A Beydoun, Dorota Szymkowiak, Rebecca Kinney, May A Beydoun, Alan B Zonderman, Jack Tsai
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
{"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}
{"title":"Addressing Enduring Health Impacts of Incarceration on Older Adults: A Call for Academic and Policy Reform.","authors":"Raya Elfadel Kheirbek, Kenzie Latham-Mintus","doi":"10.1093/gerona/glae127","DOIUrl":"10.1093/gerona/glae127","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474246","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}