Journals of Gerontology Series A-Biological Sciences and Medical Sciences最新文献

{"title":"Establishment of Baseline Urinary Antimicrobial Peptide Levels by Age: A Prospective Observational Study.","authors":"Jeffrey M Caterino, Julie A Stephens, Randell Wexler, Carlos A Camargo, Katherine M Hunold, Lai Wei, David Hains, Lauren T Southerland, Jason J Bischof, Andrew Schwaderer","doi":"10.1093/gerona/glad223","DOIUrl":"10.1093/gerona/glad223","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial peptides (AMPs) are key effectors of urinary tract innate immunity. Identifying differences in urinary AMP levels between younger and older adults is important in understanding older adults' susceptibility and response to urinary tract infections (UTI) and AMP use as diagnostic biomarkers. We hypothesized that uninfected older adults have higher urinary human neutrophil peptides 1-3 (HNP 1-3), human alpha-defensin-5 (HD-5), and human beta-defensin-2 (hBD-2), but lower urinary cathelicidin (LL-37) than younger adults.</p><p><strong>Methods: </strong>We conducted a cross-sectional study of patients aged ≥18 years completing a family medicine clinic nonacute visit. Enzyme-linked immunosorbent assays were performed for AMPs. We identified associations between age and AMPs using unadjusted and multivariable linear regression models.</p><p><strong>Results: </strong>Of the 308 subjects, 144 (46.8%) were ≥65 years of age. Comparing age ≥65 versus < 65 years, there were no significant differences in HNP 1-3 (p = .371), HD5 (p = .834), or LL-37 (p = .348) levels. Values for hBD-2 were lower in older adults versus younger (p < .001). In multivariable analyses, older males and females had significantly lower hBD-2 levels (p < .001 and p = .004). Models also showed urine leukocyte esterase was associated with increased levels of HNP 1-3 and HD5; hematuria with increased hBD-2; and urine cultures with contamination with increased HNP 1-3 and hBD-2.</p><p><strong>Conclusions: </strong>Baseline urinary HNP 1-3, HD-5, and LL-37 did not vary with age. Older adults had lower baseline hBD-2. This finding has implications for the potential use of urinary AMPs as diagnostic markers and will facilitate further investigation into the role of innate immunity in UTI susceptibility in older adults.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11083632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10296125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal Muscle Health, Physical Performance, and Lower Urinary Tract Symptoms in Older Adults: The Study of Muscle, Mobility, and Aging.","authors":"Scott R Bauer, Candace Parker-Autry, Kaiwei Lu, Steven R Cummings, Russell T Hepple, Rebecca Scherzer, Kenneth Covinsky, Peggy M Cawthon","doi":"10.1093/gerona/glad218","DOIUrl":"10.1093/gerona/glad218","url":null,"abstract":"<p><strong>Background: </strong>Lower urinary tract symptoms (LUTS) and mobility limitations are bidirectionally associated among older adults, but the role of skeletal muscle remains unknown. We evaluated cross-sectional associations of muscle health and physical performance with LUTS.</p><p><strong>Methods: </strong>We used data from 377 women and 264 men aged >70 years in the Study of Muscle, Mobility and Aging (SOMMA). LUTS and urinary bother were assessed using the LURN Symptom Index-10 (SI-10; higher = worse symptoms). Muscle mass and volume were assessed using D3-creatine dilution (D3Cr) and magnetic resonance imaging. Grip strength and peak leg power assessed upper/lower extremity physical performance. 400-m walk, Short Physical Performance Battery (SPPB), and Four Square Step Test (FSST) assessed global physical performance. Mobility Assessment Tool-short form (MAT-sf) assessed self-reported mobility. We calculated Spearman correlation coefficients adjusted for age, body mass index, multimorbidity, and polypharmacy, chi-square tests, and Fisher's Z-test to compare correlations.</p><p><strong>Results: </strong>Among women, LURN SI-10 total scores were inversely correlated with FSST (rs = 0.11, p = .045), grip strength (rs = -0.15, p = .006), and MAT-sf (rs = -0.18, p = .001), but not other muscle and physical performance measures in multivariable models. LURN SI-10 was not associated with any of these measures among men. Forty-four percent of women in the lowest tertile of 400-m walk speed versus 24% in the highest tertile reported they were at least \"somewhat bothered\" by urinary symptoms (p < .001), whereas differences among men were not significant.</p><p><strong>Conclusions: </strong>Balance and grip strength were associated with LUTS severity in older women but not men. Associations with other muscle and physical performance measures varied by LUTS subtype but remained strongest among women.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11083634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxanthine Induces Signs of Bladder Aging With Voiding Dysfunction and Lower Urinary Tract Remodeling.","authors":"Lori A Birder, Amanda S Wolf-Johnston, Irina Zabbarova, Youko Ikeda, Anne M Robertson, Ricardo Cardozo, Fatemeh Azari, Anthony J Kanai, George A Kuchel, Edwin K Jackson","doi":"10.1093/gerona/glad171","DOIUrl":"10.1093/gerona/glad171","url":null,"abstract":"<p><strong>Background: </strong>Lower urinary tract syndrome (LUTS) is a group of urinary tract symptoms and signs that can include urinary incontinence. Advancing age is a major risk factor for LUTS; however, the underlying biochemical mechanisms of age-related LUTS remain unknown. Hypoxanthine (HX) is a purine metabolite associated with generation of tissue-damaging reactive oxygen species (ROS). This study tested the hypothesis that exposure of the adult bladder to HX-ROS over time damages key LUT elements, mimicking qualitatively some of the changes observed with aging.</p><p><strong>Methods: </strong>Adult 3-month-old female Fischer 344 rats were treated with vehicle or HX (10 mg/kg/day; 3 weeks) administered in drinking water. Targeted purine metabolomics and molecular approaches were used to assess purine metabolites and biomarkers for oxidative stress and cellular damage. Biomechanical approaches assessed LUT structure and measurements of LUT function (using custom-metabolic cages and cystometry) were also employed.</p><p><strong>Results: </strong>HX exposure increased biomarkers indicative of oxidative stress, pathophysiological ROS production, and depletion of cellular energy with declines in NAD+ levels. Moreover, HX treatment caused bladder remodeling and decreased the intercontraction interval and leak point pressure (surrogate measure to assess stress urinary incontinence).</p><p><strong>Conclusions: </strong>These studies provide evidence that in adult rats chronic exposure to HX causes changes in voiding behavior and in bladder structure resembling alterations observed with aging. These results suggest that increased levels of uro-damaging HX were associated with ROS/oxidative stress-associated cellular damage, which may be central to age-associated development of LUTS, opening up potential opportunities for geroscience-guided interventions.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11083631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9831701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of a Blood-Based Aging Biomarker Index With Death and Chronic Disease: Cardiovascular Health Study.","authors":"Xiao Zhang, Jason L Sanders, Robert M Boudreau, Alice M Arnold, Jamie N Justice, Mark A Espeland, George A Kuchel, Nir Barzilai, Lewis H Kuller, Oscar L Lopez, Stephen B Kritchevsky, Anne B Newman","doi":"10.1093/gerona/glad172","DOIUrl":"10.1093/gerona/glad172","url":null,"abstract":"<p><strong>Background: </strong>A goal of gerontology is to discover phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that are strongly associated with mortality could be used to define such a phenotype. However, the relation of such an index with multiple chronic conditions warrants further exploration.</p><p><strong>Methods: </strong>A biomarker index (BI) was constructed in the Cardiovascular Health Study (N = 3 197), with a mean age of 74 years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor-1, interleukin-6, amino-terminal pro-B-type natriuretic peptide, cystatin-C, C-reactive protein, tumor necrosis factor-alpha soluble receptor 1, fasting insulin, and fasting glucose, and was built based on their relationships with mortality. Cox proportional hazards models predicting a composite of death and chronic disease involving cardiovascular disease, dementia, and cancer were calculated with 6 years of follow-up.</p><p><strong>Results: </strong>The hazard ratio (HR, 95% CI) for the composite outcome of death or chronic disease per category of BI was 1.65 (1.52, 1.80) and 1.75 (1.58, 1.94) in women and men, respectively. The HR (95% CI) per 5 years of age was 1.57 (1.48, 1.67) and 1.55 (1.44, 1.67) in women and men, respectively. Moreover, BI could attenuate the effect of age on the composite outcome by 16.7% and 22.0% in women and men, respectively.</p><p><strong>Conclusions: </strong>Biomarker index was significantly and independently associated with a composite outcome of death and chronic disease, and attenuated the effect of age. The BI that is composed of plasma biomarkers may be a practical intermediate phenotype for interventions aiming to modify the course of aging.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10799760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9886802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mid-Life Vascular Risk and Rate of Physical Function Decline Among Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study.","authors":"Laura F Skow, A Richey Sharrett, Rebecca F Gottesman, Josef Coresh, Jennifer A Deal, Priya Palta, Kevin J Sullivan, Michael E Griswold, Jennifer A Schrack, B Gwen Windham","doi":"10.1093/gerona/glad210","DOIUrl":"10.1093/gerona/glad210","url":null,"abstract":"<p><strong>Background: </strong>Physical function and its decline in older age may be connected to treatable vascular risk factors in mid-life. This study aimed to evaluate whether these factors affect the underlying rate of decline.</p><p><strong>Methods: </strong>This prospective cohort included 5 481 older adults aged 67-91 in the Atherosclerosis Risk in Communities Study (mean [standard deviation {SD}] age = 75.8 [5.0], 58% women, 21% Black race) without a history of stroke. The main outcome was the rate of Short Physical Performance Battery (SPPB) decline over a median late-life follow-up of 4.8 years. Primary mid-life (aged 45-64) exposures were Visit 1 hypertension (>140/90 mm Hg or treatment), diabetes (>126 mg/dL or treatment), high cholesterol (>240 mg/dL or treatment), and smoking, and number of decades of vascular risk exposure across Visits 1-4.</p><p><strong>Results: </strong>The average adjusted rate of SPPB decline (points per 5 years) for older adults was -0.79 (confidence interval [CI]: -0.87, 0.71) and was accelerated by mid-life hypertension (+57% decline vs normotension: additional decline of -0.47, 95% CI: -0.64, -0.30), diabetes (+73% decline vs no diabetes: additional decline of -0.67, 95% CI: -1.09, -0.24), elevated systolic blood pressure (+17% decline per SD: -0.16, 95% CI: -0.23, -0.10), and elevated fasting blood glucose (+16% decline per SD: -0.015, 95% CI: -0.24, -0.06). Each decade greater mid-life exposure to hypertension (+32% decline: -0.93, 95% CI: -1.25, -0.61) and diabetes (+35% decline: -1.03, 95% CI: -1.68, -0.38) was associated with faster SPPB decline.</p><p><strong>Conclusions: </strong>Mid-life control of blood pressure and diabetes may offset aging-related functional decline.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10809050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10143016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Life-Space Mobility: Normative Values From a National Cohort of U.S. Older Adults.","authors":"Alexander X Lo, Virginia G Wadley, Cynthia J Brown, D Leann Long, Michael Crowe, Virginia J Howard, Richard E Kennedy","doi":"10.1093/gerona/glad176","DOIUrl":"10.1093/gerona/glad176","url":null,"abstract":"<p><strong>Background: </strong>Life-space mobility, which measures the distance, frequency, and independence achieved as individuals move through their community, is one of the most important contributors to healthy aging. The University of Alabama at Birmingham Life-Space Assessment (LSA) is the most commonly used measure of life-space mobility in older adults, yet U.S. national norms for LSA have not previously been reported. This study reports such norms based on age and sex among community-dwelling older adults.</p><p><strong>Methods: </strong>A cross-sectional analysis using data from the national REasons for Geographic and Racial Disparities in Stroke cohort study. LSA data were available for 10 118 Black and White participants over age 50, which were grouped by age (in 5-year increments) and sex, weighted for the U.S. national population. Correlations were calculated between LSA and measures of functional and cognitive impairment and physical performance.</p><p><strong>Results: </strong>The weighted mean LSA ranged from 102.9 for 50-54-year-old males to 69.5 for males aged 85 and older, and from 102.1 for 50-54-year-old females to 60.1 for females aged 85 and older. LSA was strongly correlated with measures of timed walking, activities of daily living, cognition, depressive symptoms, and quality of life (all p < .001).</p><p><strong>Conclusions: </strong>We report U.S. national norms for LSA among community-dwelling Black and White older adults. These norms can serve as a reference tool for determining if clinical and research samples have greater or lesser life-space mobility than typical older adults in the United States for their age and sex.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10803118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10210896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Exercise Effect on Neurocognitive Function Among Cognitively Normal Late-Middle-Aged Adults With/Without Genetic Risk of AD: The Moderating Role of Exercise Volume and APOE Genotype.","authors":"Yu-Kai Chang, Jennifer L Etnier, Ruei-Hong Li, Fei-Fei Ren, Jing-Yi Ai, Chien-Heng Chu","doi":"10.1093/gerona/glad179","DOIUrl":"10.1093/gerona/glad179","url":null,"abstract":"<p><strong>Background: </strong>Acute exercise is a behavior that benefits cognitive function; however, its effect on populations with different risks for Alzheimer's disease (AD) and the role of exercise variance and Apolipoprotein E (APOE) genotype on this effect remains unknown. This study explores the acute exercise effect on behavioral and neurocognitive function, and its potential moderation by exercise intensity and duration and APOE genetic risk.</p><p><strong>Methods: </strong>Fifty-one cognitively normal adults (~36% APOE ε4 carriers) performed the Stroop task under a rest condition and 3 exercise conditions while electroencephalographic activity was assessed.</p><p><strong>Results: </strong>Acute exercise improved cognitive performance assessed through both behavioral and neuroelectrical indices. These benefits were observed regardless of adjustments of intensity and duration at a predetermined exercise volume as well as being evident irrespective of APOE ɛ4 carrier status.</p><p><strong>Conclusions: </strong>Acute exercise could be proposed as a lifestyle intervention to benefit neurocognitive function in populations with and without genetic risk of AD. Future exploration should further the precise exercise prescription and also the mechanisms underlying the beneficial effects of acute exercise for neurocognitive function.</p><p><strong>Clinical trials registration number: </strong>NCT05591313.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9908811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers of Alzheimer's Disease and Cerebrovascular Disease in Relation to Depressive Symptomatology in Individuals With Subjective Cognitive Decline.","authors":"Mariola Zapater-Fajarí, Patricia Diaz-Galvan, Nira Cedres, Therese Rydberg Sterner, Lina Rydén, Simona Sacuiu, Margda Waern, Anna Zettergren, Henrik Zetterberg, Kaj Blennow, Silke Kern, Vanesa Hidalgo, Alicia Salvador, Eric Westman, Ingmar Skoog, Daniel Ferreira","doi":"10.1093/gerona/glad216","DOIUrl":"10.1093/gerona/glad216","url":null,"abstract":"<p><strong>Background: </strong>Subjective cognitive decline (SCD) has gained recent interest as a potential harbinger of neurodegenerative diseases such as Alzheimer's disease (AD) and cerebrovascular disease (CVD). In addition, SCD can be related to depressive symptomatology. However, the association between AD and CVD biomarkers, depressive symptomatology, and SCD is still unclear. We investigated the association of AD and CVD biomarkers and depressive symptomatology with SCD in individuals with subjective memory complaints (SCD-memory group) and individuals with subjective concentration complaints (SCD-concentration group).</p><p><strong>Methods: </strong>We recruited a population-based cohort of 217 individuals (all aged 70 years, 53% female participants, 119 SCD-memory individuals, 23 SCD-concentration individuals, and 89 controls). AD and CVD were assessed through cerebrospinal fluid levels of the Aβ42/40 ratio and phosphorylated tau, and white matter signal abnormalities on magnetic resonance imaging, respectively. Associations between biomarkers, depressive symptomatology, and SCD were tested via logistic regression and correlation analyses.</p><p><strong>Results: </strong>We found a significant association between depressive symptomatology with SCD-memory and SCD-concentration. Depressive symptomatology was not associated with AD and CVD biomarkers. Both the phosphorylated tau biomarker and depressive symptomatology predicted SCD-memory, and the Aβ42/40 ratio and depressive symptomatology predicted SCD-concentration.</p><p><strong>Conclusions: </strong>The role of depressive symptomatology in SCD may differ depending on the stage within the spectrum of preclinical AD (as determined by amyloid-beta and tau positivity), and does not seem to reflect AD pathology. Our findings contribute to the emerging field of subclinical depressive symptomatology in SCD and clarify the association of different types of subjective complaints with distinct syndromic and biomarker profiles.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10803123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10296111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Neighborhood Deprivation and Depressive Symptoms With Epigenetic Age Acceleration: Evidence From the Canadian Longitudinal Study on Aging.","authors":"Divya Joshi, Frank J van Lenthe, Martijn Huisman, Erik R Sund, Steinar Krokstad, Mauricio Avendano, Parminder Raina","doi":"10.1093/gerona/glad118","DOIUrl":"10.1093/gerona/glad118","url":null,"abstract":"<p><strong>Background: </strong>Neighborhood deprivation and depression have been linked to epigenetic age acceleration. The next-generation epigenetic clocks including the DNA methylation (DNAm) GrimAge, and PhenoAge have incorporated clinical biomarkers of physiological dysregulation by selecting cytosine-phosphate-guanine sites that are associated with risk factors for disease, and have shown improved accuracy in predicting morbidity and time-to-mortality compared to the first-generation clocks. The aim of this study is to examine the association between neighborhood deprivation and DNAm GrimAge and PhenoAge acceleration in adults, and assess interaction with depressive symptoms.</p><p><strong>Methods: </strong>The Canadian Longitudinal Study on Aging recruited 51 338 participants aged 45-85 years across provinces in Canada. This cross-sectional analysis is based on a subsample of 1 445 participants at baseline (2011-2015) for whom epigenetic data were available. Epigenetic age acceleration (years) was assessed using the DNAm GrimAge and PhenoAge, and measured as residuals from regression of the biological age on chronological age.</p><p><strong>Results: </strong>A greater neighborhood material and/or social deprivation compared to lower deprivation (b = 0.66; 95% confidence interval [CI] = 0.21, 1.12) and depressive symptoms scores (b = 0.07; 95% CI = 0.01, 0.13) were associated with higher DNAm GrimAge acceleration. The regression estimates for these associations were higher but not statistically significant when epigenetic age acceleration was estimated using DNAm PhenoAge. There was no evidence of a statistical interaction between neighborhood deprivation and depressive symptoms.</p><p><strong>Conclusions: </strong>Depressive symptoms and neighborhood deprivation are independently associated with premature biological aging. Policies that improve neighborhood environments and address depression in older age may contribute to healthy aging among older adults living in predominantly urban areas.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10809038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9588449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Counteracting Age-Related Netrin-1 Signaling Insufficiency Ameliorates Endothelial Cell Senescence and Angiogenesis Impairment.","authors":"Zhen Yang, Han Li, Dan Yan, Pengcheng Luo, Yuqi Guan, Mandi Luo, Hao Nie, Yi Huang, Le Zhang, Lei Ruan, Jinhua Yan, Cuntai Zhang","doi":"10.1093/gerona/glad194","DOIUrl":"10.1093/gerona/glad194","url":null,"abstract":"<p><p>Senescent cells that accumulate are regarded as promising therapeutic targets. However, senolytic therapy failed to achieve satisfactory results. We previously discovered that young human plasma improved vascular endothelial cell senescence, and UNC5B might be a novel intervention target. Netrin-1, as a natural ligand of UNC5B, plays roles in multiple age-related vascular disorders, but its involvement in aging is still unclear. Here, we observed a significant decrease in plasma Netrin-1 levels in old healthy subjects compared to the young. In vivo, adeno-associated-virus-mediated delivery of Netrin-1 into aged mice significantly improved functional recovery in a model of hindlimb ischemia, promoted angiogenesis in ischemic tissues, and activated the endothelial nitric oxide synthase. Furthermore, we revealed that low-dose Netrin-1 recombinant protein significantly reduced senescence-associated-β-galactosidase-positive cells, inhibited the P53 pathway, promoted cell migration, increased tubule formation, and elevated nitric oxide production in senescent endothelial cells. However, UNC5B inhibition blocked the pro-angiogenesis effect of low-dose Netrin-1 on senescent cells or aortic rings. In summary, this study depicts that modulating Netrin-1 signaling can result in improved vascular health and Netrin-1 may have therapeutic potential for age-related ischemic diseases.</p>","PeriodicalId":49953,"journal":{"name":"Journals of Gerontology Series A-Biological Sciences and Medical Sciences","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}