Translational Medicine of Aging最新文献

{"title":"The efficacy and tolerability of intermittent prandial acarbose to reduce glucose spikes in healthy individuals","authors":"A. Isman ,&nbsp;A. Nyquist ,&nbsp;M. Moel ,&nbsp;X. Zhang ,&nbsp;S. Zalzala","doi":"10.1016/j.tma.2023.04.002","DOIUrl":"10.1016/j.tma.2023.04.002","url":null,"abstract":"<div><p>Acarbose is an α-glucosidase inhibitor that slows the digestion of carbohydrates and can prevent sharp increases in blood sugar levels after meals (spikes). Excessive postprandial blood glucose spikes have been associated with chronic conditions, increase all-cause mortality, and may contribute to aging. Therefore, the prevention of glucose spikes may contribute to the preservation of human healthspan. Indeed, acarbose has been associated with increased lifespan in animal models. However, its tolerability profile has limited acarbose use in healthy individuals. We hypothesized that using low-dose acarbose right before the occasional high-carbohydrate meal may prevent glucose spikes in healthy individuals. We performed a prospective clinical study to evaluate the tolerability and efficacy of acarbose in healthy individuals. Participants were randomized into two arms, each performing two control tests and two treatment tests. Continuous glucose monitor (CGM) measurements were collected for 2 h after high carbohydrate meals with or without pre-meal 50 mg acarbose intake. Tolerability was assessed using questionnaires. Twelve patients had evaluable results. Acarbose pretreatment resulted in reductions in CGM glucose measurements, with a significant decrease in glucose levels at the start, after 15 min, and at peak glucose levels. Few participants reported acarbose adverse events, and these included flatulence, bloating, nausea, abdominal pain, and stomach aches. No statistical difference in tolerability was detected between periods with and without acarbose. In conclusion, treatment with 50 mg of acarbose before meals was found to be well tolerated and efficacious in blunting the postprandial glucose spike by over 17% in healthy individuals.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"7 ","pages":"Pages 12-19"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47474562","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":"Impact of frailty status on clinical outcomes in patients receiving peritoneal dialysis","authors":"Christy Abraham ,&nbsp;Joanne Collier ,&nbsp;Henry H.L. Wu ,&nbsp;Joanne Martin ,&nbsp;Helen Hurst ,&nbsp;Dimitrios Poulikakos ,&nbsp;David Lewis ,&nbsp;Rajkumar Chinnadurai","doi":"10.1016/j.tma.2023.11.002","DOIUrl":"https://doi.org/10.1016/j.tma.2023.11.002","url":null,"abstract":"","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"7 ","pages":"Pages 128-132"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468501123000184/pdfft?md5=f8cff947fa8639ee939028fb48ddb60a&pid=1-s2.0-S2468501123000184-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138436545","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":"Age-related changes of GAD1 mRNA expression in the central inferior colliculus","authors":"Christina C. Koehler ,&nbsp;Laila S. Almassri ,&nbsp;Nick Tokar ,&nbsp;Amir M. Mafi ,&nbsp;Mitchell J. O'Hara ,&nbsp;Jesse W. Young ,&nbsp;Jeffrey G. Mellott","doi":"10.1016/j.tma.2023.04.001","DOIUrl":"10.1016/j.tma.2023.04.001","url":null,"abstract":"<div><p>Encoding sounds with a high degree of temporal precision is an essential task for the inferior colliculus (IC) to perform and maintain the accurate processing of sounds and speech. However, the age-related reduction of GABAergic neurotransmission in the IC interrupts temporal precision and likely contributes to presbycusis. As presbycusis often manifests at high or low frequencies specifically, we sought to determine if the expression of mRNA for glutamic decarboxylase 1 (GAD1) is downregulated non-uniformly across the tonotopic axis or cell size range in the aging IC. Using single molecule in situ fluorescent hybridization across young, middle age and old Fisher Brown Norway rats (an aging model that acquires low frequency presbycusis) we quantified individual GAD1 mRNA in small, medium and large GABAergic cells. Our results demonstrate that small GABAergic cells in low frequency regions had ∼58% less GAD1 in middle age and continued to decline into old age. In contrast, the amount of GAD1 mRNA in large cells in low frequency regions significantly increased with age. As several studies have shown that downregulation of GAD1 decreases the release of GABA, we interpret our results in two ways. First, the onset of presbycusis may be driven by small GABAergic cells downregulating GAD1. Second, as previous studies demonstrate that GAD67 expression is broadly downregulated in the old IC, perhaps the translation of GAD1 to GAD67 is interrupted in large GABAergic IC cells during aging. These results point to a potential genetic mechanism explaining reduced temporal precision in the aging IC, and in turn, presbycusis.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"7 ","pages":"Pages 20-32"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42876597","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":"The protective role of cognitive reserve on sleeping disorders on an aging population. A cross-sectional study","authors":"Barbara Colombo ,&nbsp;Simona C.S. Caravita ,&nbsp;Marie Hayes","doi":"10.1016/j.tma.2023.06.006","DOIUrl":"10.1016/j.tma.2023.06.006","url":null,"abstract":"<div><p>Sleep disorders and depression have been identified as risk factors for aging-related problems. This cross-sectional studiy explored the protective role of the cognitive reserve on a sample of 377 healthy aging adults. After assessing participants’ cognitive reserve (CR) in an extensive and comprehensive way, participants also filled out self-report scales aimed at measuring their sleep quality (PSQI - Pittsburgh Sleep Quality Index) and depressive symptoms. A series of regression models and path analyses showed that higher CR levels predicted lower PSQI scores overall, even after controlling for depressive symptoms, age, and gender. Depressive symptoms had significant role as a moderators of the effect of CR on sleep disorders. The possible effects of interventions aimed at increasing the CR in preventing the incidence of sleep disorders, cognitive decline, and other aging-related disorders are discussed.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"7 ","pages":"Pages 75-79"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48588633","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":"B and T cell subsets in elderly with frailty syndrome","authors":"Gabriela Lucena de Almeida Oliveira ,&nbsp;Eduardo Jorge Abrantes da Fonte ,&nbsp;Maria Eduarda da Costa Brandão Justino ,&nbsp;Leuridan Cavalcante Torres","doi":"10.1016/j.tma.2023.10.001","DOIUrl":"10.1016/j.tma.2023.10.001","url":null,"abstract":"<div><h3>Background</h3><p>Aging is related to changes in functional reserve that progressively lead to increased morbidity and mortality. Frailty syndrome, a common entity in older adults, is characterized by increased vulnerability to stress secondary to a decline in homeostasis caused by dysregulation.</p></div><div><h3>Objective</h3><p>The study aimed to evaluate the immunocompetence of elderly individuals with frailty syndrome.</p></div><div><h3>Methods</h3><p>A cross-sectional and translational study was carried with sixty-nine older adults with frailty syndrome (patients) and 42 healthy older adults (controls) were included.</p></div><div><h3>Results</h3><p>Low naive TCD4+ cells (P = 0.03) in patients with Frailty syndrome compared to controls. Low levels of total T cells (P = 0.01), TCD4+ (P = 0.005), and TCD4+/TCD8+ ratio (P = 0.04), memory T cells (P = 0.02), memory TCD4+ (P = 0.001), memory T CD8⁺ (P &lt; 0.0001), and high levels of naïve/memory T cells ratio (p = 0.008) in Frailty syndrome patients with age ≥70 years.</p></div><div><h3>Conclusion</h3><p>Older adults with frailty syndrome have alterations in the cellular immune response, and these findings may be associated with increased morbidity and mortality in these patients.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"7 ","pages":"Pages 118-127"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468501123000123/pdfft?md5=bbc3efc735287780cb5f1897f28338af&pid=1-s2.0-S2468501123000123-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135455036","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":"Proteostasis defects: Medicinal challenges of imperfect aging & neurodegeneration","authors":"Prashant Kumar ,&nbsp;Akash Choudhary ,&nbsp;Sumit Kinger ,&nbsp;Yuvraj Anandrao Jagtap ,&nbsp;Ankur Rakesh Dubey ,&nbsp;Ravi Kumar Gutti ,&nbsp;Deepak Chitkara ,&nbsp;Anil K. Suresh ,&nbsp;Amit Mishra","doi":"10.1016/j.tma.2023.09.001","DOIUrl":"https://doi.org/10.1016/j.tma.2023.09.001","url":null,"abstract":"<div><p>A prolonged healthy life is based on the optimal activity of an organism’s organ systems, and healthy cells are at the core of this proper functioning. Cellular homeostasis is of utmost importance, and a cell deploys several cytoprotective mechanisms to maintain this balance. One such mechanism is protein quality control (PQC) to preserve proteostasis and maintain functionality of proteins. In PQC, the chaperone system and proteolytic pathways like autophagy and ubiquitin-proteasome system (UPS) are primary cell devices preventing misfolding/aggregation of proteins and clearing out toxic protein aggregates and dysfunctional organelles. Aging is an unavoidable biological phenomenon observed in many organisms that negatively affects the functionality of multiple organs systems, thus reducing the life span. It constitutes a significant risk factor for impairment of PQC elements and proteostasis disruption, linked with physiological dysfunction of organelles along with other anomalies. Aging presents various medicinal challenges as it affects multiple physiological processes at once. In aging, declined PQC capacity can lead to increased incidence of several age-associated diseases, including neurodegenerative disorders. Proper maintenance and modulation of these PQC elements present an attractive therapeutic intervention opportunity for such disorders. Here, we present PQC and its components as a system affected in imperfect aging, its potential for modulation to improve healthspan and counter aging associated disorders, along with challenges linked with inherent complex nature of aging biology.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"7 ","pages":"Pages 87-97"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49749598","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":"Rationale and design of STAMINA: Senolytics to alleviate mobility issues and neurological impairments in aging, a geroscience feasibility study","authors":"Courtney L. Millar ,&nbsp;Ike Iloputaife ,&nbsp;Kathryn Baldyga ,&nbsp;Jasmin Kuo ,&nbsp;Tamara Tchkonia ,&nbsp;James L. Kirkland ,&nbsp;Thomas G. Travison ,&nbsp;Lewis A. Lipsitz","doi":"10.1016/j.tma.2023.10.004","DOIUrl":"https://doi.org/10.1016/j.tma.2023.10.004","url":null,"abstract":"<div><p>The process of cellular senescence is hypothesized to play a critical role in the development of age-related mobility and cognitive impairments, both of which precede the development of Alzheimer's disease. Therefore, senolytic compounds that eliminate senescent cells represent an alternative strategy that may help improve mobility and cognition in older adults; however, clinical trials are lacking. The goal of this paper is to describe the rationale and study design of a 12-week single arm, open label, pre-post pilot study that administers intermittent doses of two senolytic compounds, Dasatinib and quercetin (DQ), in 12 older adults ≥65 years with slow gait speed (&lt;1.0 m/s) and mild cognitive impairment. Eligible participants are asked to take 1250 mg of quercetin and 100 mg of Dasatinib orally once a day for 2 days every 2 weeks, for 6 cycles over 12 consecutive weeks. Both physical and cognitive functional assessments are administered before treatment, as well as 6- and 12- weeks after treatment. Blood and urine samples are taken pre- and post-treatment to assess biomarkers of cellular senescence. The primary outcomes of this trial are feasibility and safety of the intervention, as well as preliminary efficacy on several clinical outcomes (<em>e.g.</em>, cerebral blood flow velocity, gait speed, and biomarkers of cellular senescence). The study is approved by the Advarra IRB (#Pro00053594) and a Data Safety Monitoring Board. It is registered at <span>Clinicaltrials.gov</span><svg><path></path></svg> (Identifier: NCT05422885).The future results of this study may identify a novel approach for improving mobility and cognition in older adults, thereby preventing progression to Alzheimer's disease.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"7 ","pages":"Pages 109-117"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468501123000159/pdfft?md5=27ee0c1421828b2eb5a64e73a1385e34&pid=1-s2.0-S2468501123000159-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92016175","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":"Psychological stress and epigenetic aging in older men: The VA normative aging study","authors":"Jamaji C. Nwanaji-Enwerem ,&nbsp;Andres Cardenas ,&nbsp;Xu Gao ,&nbsp;Cuicui Wang ,&nbsp;Pantel Vokonas ,&nbsp;Avron Spiro ,&nbsp;Anwar D. Osborne ,&nbsp;Anna Kosheleva ,&nbsp;Lifang Hou ,&nbsp;Andrea A. Baccarelli ,&nbsp;Joel Schwartz","doi":"10.1016/j.tma.2023.06.003","DOIUrl":"10.1016/j.tma.2023.06.003","url":null,"abstract":"<div><p>Psychological stress remains an important risk factor for morbidity and mortality throughout the life course. However, there have been counterintuitive findings reported in previous studies of older persons that examine the relationships of perceived psychological stress with DNA methylation-based markers of aging, which also serve as predictors of morbidity and mortality (epigenetic age/clocks). We aimed to replicate and expand findings from existing work by examining relationships of self-reported stress with nine epigenetic clocks: Hannum, Horvath, Intrinsic, Extrinsic, SkinBloodClock, PhenoAge, GrimAge, DNAm Telomere Length, and Pace of Aging. We analyzed data from 607 male participants (mean age 73.2 years) of the VA Normative Aging Study with one to two study visits from 1999 to 2007 (observations = 956). Stress was assessed via the 14-item Perceived Stress Scale (PSS). Epigenetic age was calculated from DNA methylation measured in leukocytes with the HumanMethylation450 BeadChip. In linear mixed effects models adjusted for demographic/lifestyle/health factors, a standard deviation (sd) increase in PSS was associated with Horvath (β = −0.35-years, 95%CI: −0.61, −0.09, <em>P</em> = 0.008) and Intrinsic (β = −0.40-years, 95%CI: −0.67, −0.13, <em>P</em> = 0.004) epigenetic age deceleration. However, in models limited to participants with the highest levels of stress (≥75th-percentile), Horvath (β = 2.29-years, 95%CI: 0.16, 4.41, <em>P</em> = 0.04) and Intrinsic (β = 2.06-years, 95%CI: −0.17, 4.28, <em>P</em> = 0.07) age acceleration associations were observed. Our results reinforce the complexity of psychological stress and epigenetic aging relationships and lay a foundation for future studies that explore longitudinal relationships with other adult stress metrics and factors that can influence stress such as resilience measures.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"7 ","pages":"Pages 66-74"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10416788/pdf/nihms-1914979.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9996733","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":"Mitochondrial cardiomyopathy and emerging therapeutics","authors":"Jinjuan Yang ,&nbsp;Xiaoxian Zhang ,&nbsp;Meng Kou ,&nbsp;Boon Xuan Lian ,&nbsp;Zhixin Chiang ,&nbsp;Jace Chen ,&nbsp;Xiaoya Zhou ,&nbsp;Ziyue Li ,&nbsp;Jinqiu Zhang ,&nbsp;Xiao Su ,&nbsp;Qizhou Lian","doi":"10.1016/j.tma.2023.10.002","DOIUrl":"https://doi.org/10.1016/j.tma.2023.10.002","url":null,"abstract":"<div><p>Genetic mitochondrial cardiomyopathy (MCM) is a myocardial condition characterized by abnormal cardiac structure and function secondary to genetic defects. Severity can vary from asymptomatic to severe with manifestations that include heart failure, arrhythmias, and sudden cardiac death. The heterogeneity of gene mutation-provoked mitochondrial dysfunction and a variety of manifestations hamper the development of effective therapeutics. In this review, we present the common pathogenesis of mitochondrial cardiomyopathies, and the most recent promising novel therapeutic strategies for cardiac repair including use of cells or stem cells, adeno-associated virus (AAV)-based gene therapies, mitochondrial-based therapy, pharmaceutical compounds, dietary supplementation, and exercise. We discuss their respective advantages and limitations that may aid their broader clinical application. Some novel treatments remain a long way from achieving safe and effective clinical therapeutic effects.</p></div>","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"7 ","pages":"Pages 98-108"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49749730","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":"An updated landscape of cellular senescence heterogeneity: Mechanisms, technologies and senotherapies","authors":"Yu Sun","doi":"10.1016/j.tma.2023.06.001","DOIUrl":"https://doi.org/10.1016/j.tma.2023.06.001","url":null,"abstract":"","PeriodicalId":36555,"journal":{"name":"Translational Medicine of Aging","volume":"7 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49759217","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}