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Genetic and environmental determinants of bone quality: a cross-sectional analysis of the Hungarian Twin Registry. 骨质的遗传和环境决定因素:匈牙利双胞胎登记的横断面分析。
IF 5.3 2区 医学
GeroScience Pub Date : 2024-12-01 Epub Date: 2024-07-02 DOI: 10.1007/s11357-024-01265-2
Szilvia Mészáros, Márton Piroska, Tamás Leel-Őssy, Ádám Domonkos Tárnoki, Dávid László Tárnoki, Zsófia Jokkel, Helga Szabó, Éva Hosszú, Emőke Csupor, Réka Kollár, Árpád Kézdi, Ádám G Tabák, Csaba Horváth
{"title":"Genetic and environmental determinants of bone quality: a cross-sectional analysis of the Hungarian Twin Registry.","authors":"Szilvia Mészáros, Márton Piroska, Tamás Leel-Őssy, Ádám Domonkos Tárnoki, Dávid László Tárnoki, Zsófia Jokkel, Helga Szabó, Éva Hosszú, Emőke Csupor, Réka Kollár, Árpád Kézdi, Ádám G Tabák, Csaba Horváth","doi":"10.1007/s11357-024-01265-2","DOIUrl":"10.1007/s11357-024-01265-2","url":null,"abstract":"<p><p>There is abundant evidence that bone mineral content is highly heritable, while the heritability of bone quality (i.e. trabecular bone score [TBS] and quantitative ultrasound index [QUI]) is rarely investigated. We aimed to disentangle the role of genetic, shared and unique environmental factors on TBS and QUI among Hungarian twins. Our study includes 82 twin (48 monozygotic, 33 same-sex dizygotic) pairs from the Hungarian Twin Registry. TBS was determined by DXA, QUI by calcaneal bone ultrasound. To estimate the genetic and environmental effects, we utilized ACE-variance decomposition. For the unadjusted model of TBS, an AE model provided the best fit with > 80% additive genetic heritability. Adjustment for age, sex, BMI and smoking status improved model fit with 48.0% of total variance explained by independent variables. Furthermore, there was a strong dominant genetic effect (73.7%). In contrast, unadjusted and adjusted models for QUI showed an AE structure. Adjustments improved model fit and 25.7% of the total variance was explained by independent variables. Altogether 70-90% of the variance in QUI was related to additive genetic influences. We found a strong genetic heritability of bone quality in unadjusted models. Half of the variance of TBS was explained by age, sex and BMI. Furthermore, the adjusted model suggested that the genetic component of TBS could be dominant or an epistasis could be present. In contrast, independent variables explained only a quarter of the variance of QUI and the additive heritability explained more than half of all the variance.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491693","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}
引用次数: 0
Dynamics of serum exosome microRNA profile altered by chemically induced estropause and rescued by estrogen therapy in female mice. 雌性小鼠血清外泌体微RNA谱的动态变化:化学诱导的雌性绝经和雌激素治疗的挽救。
IF 5.3 2区 医学
GeroScience Pub Date : 2024-12-01 Epub Date: 2024-03-19 DOI: 10.1007/s11357-024-01129-9
Bianka Machado Zanini, Bianca Machado de Avila, Driele Neske Garcia, Jéssica Damé Hense, Gabriel Barreto Veiga, Mariana Machado Barreto, Sarah Ashiqueali, Jeffrey B Mason, Hariom Yadav, Michal Masternak, Augusto Schneider
{"title":"Dynamics of serum exosome microRNA profile altered by chemically induced estropause and rescued by estrogen therapy in female mice.","authors":"Bianka Machado Zanini, Bianca Machado de Avila, Driele Neske Garcia, Jéssica Damé Hense, Gabriel Barreto Veiga, Mariana Machado Barreto, Sarah Ashiqueali, Jeffrey B Mason, Hariom Yadav, Michal Masternak, Augusto Schneider","doi":"10.1007/s11357-024-01129-9","DOIUrl":"10.1007/s11357-024-01129-9","url":null,"abstract":"<p><p>The decline in the ovarian reserve leads to menopause and reduced serum estrogens. MicroRNAs are small non-coding RNAs, which can regulate gene expression and be secreted by cells and trafficked in serum via exosomes. Serum miRNAs regulate tissue function and disease development. Therefore, the aim of this study was to identify miRNA profiles in serum exosomes of mice induced to estropause and treated with 17β-estradiol (E2). Female mice were divided into three groups including control (CTL), injected with 4-Vinylcyclohexene diepoxide (VCD), and injected with VCD plus E2 (VCD + E<sub>2</sub>). Estropause was confirmed by acyclicity and a significant reduction in the number of ovarian follicles (p < 0.05). Body mass gain during estropause was higher in VCD and VCD + E2 compared to CTL females (p = 0.02). Sequencing of miRNAs was performed from exosomes extracted from serum, and 402 miRNAs were detected. Eight miRNAs were differentially regulated between CTL and VCD groups, seven miRNAs regulated between CTL and VCD + E2 groups, and ten miRNAs regulated between VCD and VCD + E2 groups. Only miR-200a-3p and miR-200b-3p were up-regulated in both serum exosomes and ovarian tissue in both VCD groups, suggesting that these exosomal miRNAs could be associated with ovarian activity. In the hepatic tissue, only miR-370-3p (p = 0.02) was up-regulated in the VCD + E2 group, as observed in serum. Our results suggest that VCD-induced estropause and E2 replacement have an impact on the profile of serum exosomal miRNAs. The miR-200 family was increased in serum exosomes and ovarian tissue and may be a candidate biomarker of ovarian function.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157895","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}
引用次数: 0
Neurological diagnostic tests for patients with and without delirium: a prospective observational study. 谵妄患者和无谵妄患者的神经学诊断测试:一项前瞻性观察研究。
IF 5.3 2区 医学
GeroScience Pub Date : 2024-12-01 Epub Date: 2024-06-25 DOI: 10.1007/s11357-024-01246-5
Noémie Waefler, Imen Abid, Victor Montaut, Jacques Donzé, Hervé Zender, Gregor John
{"title":"Neurological diagnostic tests for patients with and without delirium: a prospective observational study.","authors":"Noémie Waefler, Imen Abid, Victor Montaut, Jacques Donzé, Hervé Zender, Gregor John","doi":"10.1007/s11357-024-01246-5","DOIUrl":"10.1007/s11357-024-01246-5","url":null,"abstract":"<p><p>Since most of the precipitating factors of delirium are not due to neurological disorders, neurological diagnostic tests (NDTs) may be of limited value. We hypothesized that delirium has a high burden of NDTs with a low diagnostic yield. All patients admitted to the internal medicine wards of a single secondary teaching hospital between November 2019 and January 2020 were eligible. Within the first 48 h of their admission, they had a formal evaluation by a neuropsychologist to screen for presence of delirium. NDTs (brain MRI, brain CT, electroencephalography (EEG), and lumbar puncture) performed during the hospital stay were compared between patients with and without delirium using a logistic regression model stratified by a propensity score. The proportions of diagnostic yield (acute anomalies that changed the treatment management) provided by each type of examination were compared. Of 217 patients included, 19/32 patients (61%) with delirium had one or more NDTs, compared to 48/185 (26%) without delirium (adjusted OR 2.7; 95%CI 1.1-6.7; p = 0.027). The proportions of NDT results affecting management for patients with and without delirium were 13 and 20% for brain CT scans (p = 0.71), 29 and 38% for brain MRI (p = 0.99), and 20 and 10% for EEGs (p = 0.99), respectively. The higher proportion of NDTs performed on patients with delirium was associated with a low diagnostic yield, although not statistically different from those performed among inpatients without delirium. There is a need for restrictive, evidence-based guidelines to help with the work-up for patients with delirium.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446065","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}
引用次数: 0
Age-related decline in cognitive flexibility and inadequate preparation: evidence from task-state network analysis. 与年龄有关的认知灵活性下降和准备不足:任务状态网络分析的证据。
IF 5.3 2区 医学
GeroScience Pub Date : 2024-12-01 Epub Date: 2024-03-22 DOI: 10.1007/s11357-024-01135-x
Haishuo Xia, Ting Li, Yongqing Hou, Zijin Liu, Antao Chen
{"title":"Age-related decline in cognitive flexibility and inadequate preparation: evidence from task-state network analysis.","authors":"Haishuo Xia, Ting Li, Yongqing Hou, Zijin Liu, Antao Chen","doi":"10.1007/s11357-024-01135-x","DOIUrl":"10.1007/s11357-024-01135-x","url":null,"abstract":"<p><p>Behavioral evidence showed decreased cognitive flexibility in older adults. However, task-based network mechanisms of cognitive flexibility in aging (CFA) remain unclear. Here, we provided the first task-state network evidence that CFA was associated with inadequate preparation for switching trials by revealing age-related changes in functional integration. We examined functional integration in a letter-number switch task that distinguished between the cue and target stages. Both young and older adults showed decreased functional integration from the cue stage to the target stage, indicating that control-related processes were executed as the task progressed. However, compared to young adults, older adults showed less cue-to-target reduction in functional integration, which was primarily driven by higher network integration in the target stage. Moreover, less cue-to-target reductions were correlated with age-related decreases in task performance in the switch task. To sum up, compared to young adults, older adults pre-executed less control-related processes in the cue stage and more control-related processes in the target stage. Therefore, the decline in cognitive flexibility in older adults was associated with inadequate preparation for the impending demands of cognitive switching. This study offered novel insights into network mechanisms underlying CFA. Furthermore, we highlighted that training the function of brain networks, in conjunction with providing more preparation time for older adults, may be beneficial to their cognitive flexibility.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184161","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}
引用次数: 0
Integrated renal and sympathetic mechanisms underlying the development of sex- and age-dependent hypertension and the salt sensitivity of blood pressure. 肾脏和交感神经的综合机制是性别和年龄依赖性高血压以及血压盐敏感性发展的基础。
IF 5.3 2区 医学
GeroScience Pub Date : 2024-12-01 Epub Date: 2024-07-08 DOI: 10.1007/s11357-024-01266-1
Alissa A Frame, Kayla M Nist, Kiyoung Kim, Franco Puleo, Jesse D Moreira, Hailey Swaldi, James McKenna, Richard D Wainford
{"title":"Integrated renal and sympathetic mechanisms underlying the development of sex- and age-dependent hypertension and the salt sensitivity of blood pressure.","authors":"Alissa A Frame, Kayla M Nist, Kiyoung Kim, Franco Puleo, Jesse D Moreira, Hailey Swaldi, James McKenna, Richard D Wainford","doi":"10.1007/s11357-024-01266-1","DOIUrl":"10.1007/s11357-024-01266-1","url":null,"abstract":"<p><p>Aging is a non-modifiable understudied risk factor for hypertension. We hypothesized that sympathetically mediated activation of renal sodium reabsorption drives age-dependent hypertension and the salt sensitivity of blood pressure (BP). Using 3-, 8-, and 16-month-old male and female Sprague-Dawley rats as a model of normal aging, we assessed BP, indices of sympathetic tone, and the physiological responses to acute and chronic sodium challenge including sodium chloride cotransporter (NCC) regulation. The effects of renal nerve ablation and NCC antagonism were assessed in hypertensive male rats. We observed sex-dependent impaired renal sodium handling (24 h sodium balance (meq), male 3-month 0.36 ± 0.1 vs. 16-month 0.84 ± 0.2; sodium load excreted during 5% bodyweight isotonic saline volume expansion (%) male 3-month 77 ± 5 vs. 16-month 22 ± 8), hypertension (MAP (mmHg) male 3-month 123 ± 4 vs. 16-month 148 ± 6), and the salt sensitivity of BP in aged male, but not female, rats. Attenuated sympathoinhibitory afferent renal nerve (ARN) responses contributed to increased sympathetic tone and hypertension in male rats. Increased sympathetic tone contributes to renal sodium retention, in part through increased NCC activity via a dysfunctional with-no-lysine kinase-(WNK) STE20/SPS1-related proline/alanine-rich kinase signaling pathway, to drive hypertension and the salt sensitivity of BP in aged male rats. NCC antagonism and renal nerve ablation, which reduced WNK dysfunction and decreased NCC activity, attenuated age-dependent hypertension in male Sprague-Dawley rats. The contribution of an impaired sympathoinhibitory ARN reflex to sex- and age-dependent hypertension in an NCC-dependent manner, via an impaired WNK1/WNK4 dynamic, suggests this pathway as a mechanism-based target for the treatment of age-dependent hypertension.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554700","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}
引用次数: 0
A systematic review of diet and medication use among centenarians and near-centenarians worldwide. 对全球百岁老人和接近百岁老人的饮食和用药情况进行系统回顾。
IF 5.3 2区 医学
GeroScience Pub Date : 2024-12-01 Epub Date: 2024-07-05 DOI: 10.1007/s11357-024-01247-4
Zhaoli Dai, Sue Yi Lee, Srishti Sharma, Shahid Ullah, Edwin C K Tan, Henry Brodaty, Aletta E Schutte, Perminder S Sachdev
{"title":"A systematic review of diet and medication use among centenarians and near-centenarians worldwide.","authors":"Zhaoli Dai, Sue Yi Lee, Srishti Sharma, Shahid Ullah, Edwin C K Tan, Henry Brodaty, Aletta E Schutte, Perminder S Sachdev","doi":"10.1007/s11357-024-01247-4","DOIUrl":"10.1007/s11357-024-01247-4","url":null,"abstract":"<p><p>Centenarians represent a phenomenon of successful aging. This systematic review aimed to understand lifestyles and health practices, focusing on diet and medication use for healthy longevity in community-based adults 95 years or over. Medline, CINAHL, Scopus, and gray literature were searched from 1 January 2000 to 10 December 2022. Study quality was assessed using the Modified Newcastle-Ottawa Scale (mNOS). Pooled prevalence [%; 95% confidence interval] for categorical variables and pooled mean for continuous variables were estimated for demographics, weight status, lifestyle factors, medications, and health conditions. Of 3392 records screened, 34 studies were included in the review, and 71% (24/34) met the 6/8 criteria in mNOS. Centenarians/near-centenarians' ages ranged from 95 to 118 years, with 75% (71-78%) female and 78% (68-88%) living in rural areas. They had an overall healthy lifestyle: current smoking (7%; 5-9%), drinking (23%; 17-30%), normal weight (52%; 42-61%), overweight (14%; 8-20%), physical activity (23%; 20-26%), and sleep satisfaction (68%; 65-72%). Diet averaged 59.6% carbohydrate, 18.5% protein, and 29.3% fat; over 60% consumed a diverse diet, and < 20% preferred salty food, contributing to lower mortality risks and functional decline. About half used antihypertensives (49%; 14-84%) or other cardiovascular drugs (48%; 24-71%), with an average of 4.6 medications. Common health issues included impaired basic activities of daily living (54%; 33-74%), hypertension (43%; 21-65%), and dementia (41%; 23-59%). The findings of this systemic review underscore the pivotal role of dietary practice and weight management in healthcare strategies to promote healthy ageing. It also recognises rural living styles and sleep hygiene as potential factors contributing to healthy longevity.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534210","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}
引用次数: 0
Detecting aortic valve stenosis based on the non-invasive blood pressure waveform-a proof of concept study. 基于无创血压波形检测主动脉瓣狭窄--概念验证研究
IF 5.3 2区 医学
GeroScience Pub Date : 2024-12-01 Epub Date: 2024-03-20 DOI: 10.1007/s11357-024-01136-w
Eline Kho, Jimmy Schenk, Alexander P J Vlaar, Marije M Vis, Marije Wijnberge, Lotte B Stam, Martijn van Mourik, Harald T Jorstad, Henning Hermanns, Berend E Westerhof, Denise P Veelo, Bjorn J P van der Ster
{"title":"Detecting aortic valve stenosis based on the non-invasive blood pressure waveform-a proof of concept study.","authors":"Eline Kho, Jimmy Schenk, Alexander P J Vlaar, Marije M Vis, Marije Wijnberge, Lotte B Stam, Martijn van Mourik, Harald T Jorstad, Henning Hermanns, Berend E Westerhof, Denise P Veelo, Bjorn J P van der Ster","doi":"10.1007/s11357-024-01136-w","DOIUrl":"10.1007/s11357-024-01136-w","url":null,"abstract":"<p><p>The incidence of aortic valve stenosis (AoS) increases with age, and once diagnosed, symptomatic severe AoS has a yearly mortality rate of 25%. AoS is diagnosed with transthoracic echocardiography (TTE), however, this gold standard is time consuming and operator and acoustic window dependent. As AoS affects the arterial blood pressure waveform, AoS-specific waveform features might serve as a diagnostic tool. Aim of the present study was to develop a novel, non-invasive, AoS detection model based on blood pressures waveforms. This cross-sectional study included patients with AoS undergoing elective transcatheter or surgical aortic valve replacement. AoS was determined using TTE, and patients with no or mild AoS were labelled as patients without AoS, while patients with moderate or severe AoS were labelled as patients with AoS. Non-invasive blood pressure measurements were performed in awake patients. Ten minutes of consecutive data was collected. Several blood pressure-based features were derived, and the median, interquartile range, variance, and the 1st and 9th decile of the change of these features were calculated. The primary outcome was the development of a machine-learning model for AoS detection, investigating multiple classifiers and training on the area under the receiver-operating curve (AUROC). In total, 101 patients with AoS and 48 patients without AoS were included. Patients with AoS showed an increase in left ventricular ejection time (0.02 s, p = 0.001), a delayed maximum upstroke in the systolic phase (0.015 s, p < 0.001), and a delayed maximal systolic pressure (0.03 s, p < 0.001) compared to patients without AoS. With the logistic regression model, a sensitivity of 0.81, specificity of 0.67, and AUROC of 0.79 were found. The majority of the population without AoS was male (85%), whereas in the population with AoS this was evenly distributed (54% males). Age was significantly (5 years, p < 0.001) higher in the population with AoS. In the present study, we developed a novel model able to distinguish no to mild AoS from moderate to severe AoS, based on blood pressure features with high accuracy. Clinical registration number: The study entailing patients with TAVR treatment was registered at ClinicalTrials.gov (NCT03088787, https://clinicaltrials.gov/ct2/show/NCT03088787 ). The study with elective cardiac surgery patients was registered with the Netherland Trial Register (NL7810, https://trialsearch.who.int/Trial2.aspx?TrialID=NL7810 ).</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174245","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}
引用次数: 0
Modulation of neural gene networks by estradiol in old rhesus macaque females. 雌二醇对老年猕猴神经基因网络的影响
IF 5.3 2区 医学
GeroScience Pub Date : 2024-12-01 Epub Date: 2024-03-20 DOI: 10.1007/s11357-024-01133-z
Rita Cervera-Juanes, Kip D Zimmerman, Larry Wilhelm, Dongqin Zhu, Jessica Bodie, Steven G Kohama, Henryk F Urbanski
{"title":"Modulation of neural gene networks by estradiol in old rhesus macaque females.","authors":"Rita Cervera-Juanes, Kip D Zimmerman, Larry Wilhelm, Dongqin Zhu, Jessica Bodie, Steven G Kohama, Henryk F Urbanski","doi":"10.1007/s11357-024-01133-z","DOIUrl":"10.1007/s11357-024-01133-z","url":null,"abstract":"<p><p>The postmenopausal decrease in circulating estradiol (E2) levels has been shown to contribute to several adverse physiological and psychiatric effects. To elucidate the molecular effects of E2 on the brain, we examined differential gene expression and DNA methylation (DNAm) patterns in the nonhuman primate brain following ovariectomy (Ov) and subsequent subcutaneous bioidentical E2 chronic treatment. We identified several dysregulated molecular networks, including MAPK signaling and dopaminergic synapse response, that are associated with ovariectomy and shared across two different brain areas, the occipital cortex (OC) and prefrontal cortex (PFC). The finding that hypomethylation (p = 1.6 × 10<sup>-51</sup>) and upregulation (p = 3.8 × 10<sup>-3</sup>) of UBE2M across both brain regions provide strong evidence for molecular differences in the brain induced by E2 depletion. Additionally, differential expression (p = 1.9 × 10<sup>-4</sup>; interaction p = 3.5 × 10<sup>-2</sup>) of LTBR in the PFC provides further support for the role E2 plays in the brain, by demonstrating that the regulation of some genes that are altered by ovariectomy may also be modulated by Ov followed by hormone replacement therapy (HRT). These results present real opportunities to understand the specific biological mechanisms that are altered with depleted E2. Given E2's potential role in cognitive decline and neuroinflammation, our findings could lead to the discovery of novel therapeutics to slow cognitive decline. Together, this work represents a major step toward understanding molecular changes in the brain that are caused by ovariectomy and how E2 treatment may revert or protect against the negative neuro-related consequences caused by a depletion in estrogen as women approach menopause.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174246","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}
引用次数: 0
Relationship of psychotropic medication use with physical function among postmenopausal women. 绝经后妇女服用精神药物与身体功能的关系。
IF 5.3 2区 医学
GeroScience Pub Date : 2024-12-01 Epub Date: 2024-03-22 DOI: 10.1007/s11357-024-01141-z
Hind A Beydoun, May A Beydoun, Edward Kwon, Brook T Alemu, Alan B Zonderman, Robert Brunner
{"title":"Relationship of psychotropic medication use with physical function among postmenopausal women.","authors":"Hind A Beydoun, May A Beydoun, Edward Kwon, Brook T Alemu, Alan B Zonderman, Robert Brunner","doi":"10.1007/s11357-024-01141-z","DOIUrl":"10.1007/s11357-024-01141-z","url":null,"abstract":"<p><p>To examine cross-sectional and longitudinal relationships of psychotropic medications with physical function after menopause. Analyses involved 4557 Women's Health Initiative Long Life Study (WHI-LLS) participants (mean age at WHI enrollment (1993-1998): 62.8 years). Antidepressant, anxiolytic, and sedative/hypnotic medications were evaluated at WHI enrollment and 3-year follow-up visits. Performance-based physical function [Short Physical Performance Battery (SPPB)] was assessed at the 2012-2013 WHI-LLS visit. Self-reported physical function [RAND-36] was examined at WHI enrollment and the last available follow-up visit-an average of 22 [±2.8] (range: 12-27) years post-enrollment. Multivariable regression models controlled for socio-demographic, lifestyle, and health characteristics. Anxiolytics were not related to physical function. At WHI enrollment, antidepressant use was cross-sectionally related to worse self-reported physical function defined as a continuous (β = -6.27, 95% confidence interval [CI]: -8.48, -4.07) or as a categorical (< 78 vs. ≥ 78) (odds ratio [OR] = 2.10, 95% CI: 1.48, 2.98) outcome. Antidepressant use at WHI enrollment was also associated with worse performance-based physical function (SPPB) [< 10 vs. ≥ 10] (OR = 1.53, 95% CI: 1.05, 2.21) at the 2012-2013 WHI-LLS visit. Compared to non-users, those using sedative/hypnotics at WHI enrollment but not at the 3-year follow-up visit reported a faster decline in physical function between WHI enrollment and follow-up visits. Among postmenopausal women, antidepressant use was cross-sectionally related to worse self-reported physical function, and with worse performance-based physical function after > 20 years of follow-up. Complex relationships found for hypnotic/sedatives were unexpected and necessitate further investigation.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189641","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}
引用次数: 0
Clinical biomarker-based biological age predicts deaths in Brazilian adults: the ELSA-Brasil study. 基于临床生物标志物的生物年龄预测巴西成年人的死亡:ELSA-Brasil 研究。
IF 5.3 2区 医学
GeroScience Pub Date : 2024-12-01 Epub Date: 2024-05-16 DOI: 10.1007/s11357-024-01186-0
Amanda Viana Machado, Juliana Freitas de Mello E Silva, Enrico Antônio Colosimo, Belinda L Needham, Chams Bicalho Maluf, Luana Giatti, Lidyane V Camelo, Sandhi Maria Barreto
{"title":"Clinical biomarker-based biological age predicts deaths in Brazilian adults: the ELSA-Brasil study.","authors":"Amanda Viana Machado, Juliana Freitas de Mello E Silva, Enrico Antônio Colosimo, Belinda L Needham, Chams Bicalho Maluf, Luana Giatti, Lidyane V Camelo, Sandhi Maria Barreto","doi":"10.1007/s11357-024-01186-0","DOIUrl":"10.1007/s11357-024-01186-0","url":null,"abstract":"<p><p>Biological age is a construct that seeks to evaluate the biological wear and tear process of the organism that cannot be observed by chronological age. We estimate individuals' biological age based on biomarkers from multiple systems and validate it through its association with mortality from natural causes. Biological age was estimated in 12,109 participants (6621 women and 5488 men) from the first visit of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who had valid data for the biomarkers used in the analyses. Biological age was estimated using the Klemera and Doubal method. The difference between chronological age and biological age (Δage) was computed. Cox proportional hazard models stratified by sex were used to assess whether Δage was associated with mortality risk after a median follow-up of 9.1 years. The accuracy of the models was estimated by the area under the curve (AUC). Δage had equal mean for men and women, with greater variability for men. Cox models showed that every 1-year increase in Δage was associated with increased mortality in men (HR (95% CI) 1.21; 1.17-1.25) and women (HR (95% CI) 1.24; 1.15-1.34), independently of chronological age. Results of the AUC demonstrated that the predictive power of models that only included chronological age (AUC chronological age = 0.7396) or Δage (AUC Δage = 0.6842) was lower than those that included both, chronological age and Δage (AUC chronological age + Δage = 0.802), in men. This difference was not observed in women. We demonstrate that biological age is strongly related to mortality in both genders and is a valid predictor of death in Brazilian adults, especially among men.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943766","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}
引用次数: 0
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