GeroScience最新文献

{"title":"Semantic processing in older adults is associated with distributed neural activation which varies by association and abstractness of words.","authors":"Amanda Garcia, Ronald A Cohen, Kailey G Langer, Alexandria G O'Neal, Eric C Porges, Adam J Woods, John B Williamson","doi":"10.1007/s11357-024-01216-x","DOIUrl":"10.1007/s11357-024-01216-x","url":null,"abstract":"<p><p>The extent to which the neural systems underlying semantic processes degrade with advanced age remains unresolved, which motivated the current study of neural activation on functional magnetic resonance imaging (fMRI) during semantic judgments of associated vs. unassociated, semantic vs. rhyme, and abstract vs. rhyme word pairs. Thirty-eight older adults, 55-85 years of age, performed semantic association decision tasks in a mixed event-related block fMRI paradigm involving binary judgments as to whether word pairs were related (i.e., semantically associated). As hypothesized, significantly greater activation was evident during processing of associated (vs. unassociated) word pairs in cortical areas implicated in semantic processing, including the angular gyrus, temporal cortex, and inferior frontal cortex. Cortical areas showed greater activation to unassociated (vs. associated) word pairs, primarily within a large occipital cluster. Greater activation was evident in cortical areas when response to semantic vs. phonemic word pairs. Contrasting activation during abstract vs. concrete semantic processing revealed areas of co-activation to both semantic classes, and areas that had greater response to either abstract or concrete word pairs. Neural activation across conditions did not vary as a function of greater age, indicating only minimal age-associated perturbation in neural activation during semantic processing. Therefore, the response of the semantic hubs, semantic control, and secondary association areas appear to be largely preserved with advanced age among older adults exhibiting successful cognitive aging. These findings may provide a useful clinical contrast if compared to activation among adults experiencing cognitive decline due Alzheimer's, frontal-temporal dementia, and other neurodegenerative diseases.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"6195-6212"},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184098","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":"Glycan clock of ageing-analytical precision and time-dependent inter- and i-individual variability.","authors":"Borna Rapčan, Manshu Song, Azra Frkatović-Hodžić, Tea Pribić, Jakov Vuk, Anđelo Beletić, Maja Hanić, Julija Jurić, Petra Tominac, Josip Milas, Vedrana Ivić, Sven Viland, Sara Bonet, Branko Šego, Marija Heffer, Wei Wang, Michael P Snyder, Gordan Lauc","doi":"10.1007/s11357-024-01239-4","DOIUrl":"10.1007/s11357-024-01239-4","url":null,"abstract":"<p><p>Ageing is a complex biological process with variations among individuals, leading to the development of ageing clocks to estimate biological age. Glycans, particularly in immunoglobulin G (IgG), have emerged as potential biomarkers of ageing, with changes in glycosylation patterns correlating with chronological age.For precision analysis, three different plasma pools were analysed over 26 days in tetraplicates, 312 samples in total. In short-term variability analysis, two cohorts were analysed: AstraZeneca MFO cohort of 26 healthy individuals (median age 20) and a cohort of 70 premenopausal Chinese women (median age 22.5) cohort monitored over 3 months. Long-term variability analysis involved two adult men aged 47 and 57, monitored for 5 and 10 years, respectively. Samples were collected every 3 months and 3 weeks, respectively. IgG N-glycan analysis followed a standardized approach by isolating IgG, its subsequent denaturation and deglycosylation followed by glycan cleanup and labelling. Capillary gel electrophoresis with laser-induced fluorescence (CGE-LIF) and ultra-performance liquid chromatography analyses were employed for glycan profiling. Statistical analysis involved normalization, batch correction, and linear mixed models to assess time effects on derived glycan traits.The intermediate precision results consistently exhibited very low coefficient of variation values across all three test samples. This consistent pattern underscores the high level of precision inherent in the CGE method for analysing the glycan clock of ageing. The AstraZeneca MFO cohort did not show any statistically significant trends, whereas the menstrual cycle cohort exhibited statistically significant trends in digalactosylated (G2), agalactosylated (G0) and fucosylation (F). These trends were attributed to the effects of the menstrual cycle. Long-term stability analysis identified enduring age-related trends in both subjects, showing a positive time effect in G0 and bisected N-acetylglucosamine, as well as a negative time effect in G2 and sialylation, aligning with earlier findings. Time effects measured for monogalactosylation, and F remained substantially lower than ones observed for other traits.The study found that IgG N-glycome analysis using CGE-LIF exhibited remarkably high intermediate precision. Moreover, the study highlights the short- and long-term stability of IgG glycome composition, coupled with a notable capacity to adapt and respond to physiological changes and environmental influences such as hormonal changes, disease, and interventions. The discoveries from this study propel personalized medicine forward by deepening our understanding of how IgG glycome relates to age-related health concerns. This study underscores the reliability of glycans as a biomarker for tracking age-related changes and individual health paths.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"5781-5796"},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320838","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":"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":" ","pages":"6625-6639"},"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}

{"title":"Proteomic analysis of lung responses to SARS-CoV-2 infection in aged non-human primates: clinical and research relevance.","authors":"Andreu Garcia-Vilanova, Anna Allué-Guardia, Nadine M Chacon, Anwari Akhter, Dhiraj Kumar Singh, Deepak Kaushal, Blanca I Restrepo, Larry S Schlesinger, Joanne Turner, Susan T Weintraub, Jordi B Torrelles","doi":"10.1007/s11357-024-01264-3","DOIUrl":"10.1007/s11357-024-01264-3","url":null,"abstract":"<p><p>With devastating health and socioeconomic impact worldwide, much work is left to understand the Coronavirus Disease 2019 (COVID-19), with emphasis in the severely affected elderly population. Here, we present a proteomics study of lung tissue obtained from aged vs. young rhesus macaques (Macaca mulatta) and olive baboons (Papio Anubis) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using age as a variable, we identified common proteomic profiles in the lungs of aged infected non-human primates (NHPs), including key regulators of immune function, as well as cell and tissue remodeling, and discuss the potential clinical relevance of such parameters. Further, we identified key differences in proteomic profiles between both NHP species, and compared those to what is known about SARS-CoV-2 in humans. Finally, we explored the translatability of these animal models in the context of aging and the human presentation of the COVID-19.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"6395-6417"},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537815","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":"Impact of visceral adipose tissue on longevity and metabolic health: a comparative study of gene expression in perirenal and epididymal fat of Ames dwarf mice.","authors":"Agnieszka Zaczek, Andrzej Lewiński, Małgorzata Karbownik-Lewińska, Andrea Lehoczki, Adam Gesing","doi":"10.1007/s11357-024-01131-1","DOIUrl":"10.1007/s11357-024-01131-1","url":null,"abstract":"<p><p>Emerging research underscores the pivotal role of adipose tissue in regulating systemic aging processes, particularly when viewed through the lens of the endocrine hypotheses of aging. This study delves into the unique adipose characteristics in an important animal model of aging - the long-lived Ames dwarf (df/df) mice. Characterized by a Prop1^df gene mutation, these mice exhibit a deficiency in growth hormone (GH), prolactin, and TSH, alongside extremely low circulating IGF-1 levels. Intriguingly, while surgical removal of visceral fat (VFR) enhances insulin sensitivity in normal mice, it paradoxically increases insulin resistance in Ames dwarfs. This suggests an altered profile of factors produced in visceral fat in the absence of GH, indicating a unique interplay between adipose tissue function and hormonal influences in these models. Our aim was to analyze the gene expression related to lipid and glucose metabolism, insulin pathways, inflammation, thermoregulation, mitochondrial biogenesis, and epigenetic regulation in the visceral (perirenal and epididymal) adipose tissue of Ames dwarf and normal mice. Our findings reveal an upregulation in the expression of key genes such as Lpl, Adrβ3, Rstn, Foxo1, Foxo3a, Irs1, Cfd, Aldh2, Il6, Tnfα, Pgc1α, Ucp2, and Ezh2 in perirenal and Akt1, Foxo3a, PI3k, Ir, Acly, Il6, Ring1a, and Ring 1b in epididymal fat in df/df mice. These results suggest that the longevity phenotype in Ames dwarfs, which is determined by peripubertal GH/IGF-1 levels, may also involve epigenetic reprogramming of adipose tissue influenced by hormonal changes. The increased expression of genes involved in metabolic regulation, tumor suppression, mitochondrial biogenesis, and insulin pathways in Ames dwarf mice highlights potentially beneficial aspects of this model, opening new avenues for understanding the molecular underpinnings of longevity and aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"5925-5938"},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189640","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":"The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality.","authors":"Julian Mutz, Win Lee Edwin Wong, Timothy R Powell, Allan H Young, Gavin S Dawe, Cathryn M Lewis","doi":"10.1007/s11357-024-01142-y","DOIUrl":"10.1007/s11357-024-01142-y","url":null,"abstract":"<p><p>Lithium is an established first-line treatment for bipolar disorder. Beyond its therapeutic effect as a mood stabiliser, lithium exhibits potential anti-ageing effects. This study aimed to examine the relationship between the duration of lithium use, biological ageing and mortality. The UK Biobank is an observational study of middle-aged and older adults. We tested associations between the duration of lithium use (number of prescriptions, total duration of use and duration of the first prescription period) and telomere length, frailty, metabolomic age (MileAge) delta, pulse rate and all-cause mortality. Five hundred ninety-one individuals (mean age = 57.49 years; 55% females) had been prescribed lithium. There was no evidence that the number of prescriptions (β =  - 0.022, 95% CI - 0.081 to 0.037, p = 0.47), the total duration of use (β =  - 0.005, 95% CI - 0.023 to 0.013, p = 0.57) or the duration of the first prescription period (β =  - 0.018, 95% CI - 0.051 to 0.015, p = 0.29) correlated with telomere length. There was also no evidence that the duration of lithium use correlated with frailty or MileAge delta. However, a higher prescription count and a longer duration of use was associated with a lower pulse rate. The duration of lithium use did not predict all-cause mortality. We observed no evidence of associations between the duration of lithium use and biological ageing markers, including telomere length. Our findings suggest that the potential anti-ageing effects of lithium do not differ by the duration of use.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"5981-5994"},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305392","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":"Linking peripheral atherosclerosis to blood-brain barrier disruption: elucidating its role as a manifestation of cerebral small vessel disease in vascular cognitive impairment.","authors":"Ádám Nyúl-Tóth, Roland Patai, Anna Csiszar, Anna Ungvari, Rafal Gulej, Peter Mukli, Andriy Yabluchanskiy, Zoltan Benyo, Peter Sotonyi, Calin I Prodan, Eric M Liotta, Peter Toth, Fanny Elahi, Péter Barsi, Pál Maurovich-Horvat, Farzaneh A Sorond, Stefano Tarantini, Zoltan Ungvari","doi":"10.1007/s11357-024-01194-0","DOIUrl":"10.1007/s11357-024-01194-0","url":null,"abstract":"<p><p>Aging plays a pivotal role in the pathogenesis of cerebral small vessel disease (CSVD), contributing to the onset and progression of vascular cognitive impairment and dementia (VCID). In older adults, CSVD often leads to significant pathological outcomes, including blood-brain barrier (BBB) disruption, which in turn triggers neuroinflammation and white matter damage. This damage is frequently observed as white matter hyperintensities (WMHs) in neuroimaging studies. There is mounting evidence that older adults with atherosclerotic vascular diseases, such as peripheral artery disease, ischemic heart disease, and carotid artery stenosis, face a heightened risk of developing CSVD and VCID. This review explores the complex relationship between peripheral atherosclerosis, the pathogenesis of CSVD, and BBB disruption. It explores the continuum of vascular aging, emphasizing the shared pathomechanisms that underlie atherosclerosis in large arteries and BBB disruption in the cerebral microcirculation, exacerbating both CSVD and VCID. By reviewing current evidence, this paper discusses the impact of endothelial dysfunction, cellular senescence, inflammation, and oxidative stress on vascular and neurovascular health. This review aims to enhance understanding of these complex interactions and advocate for integrated approaches to manage vascular health, thereby mitigating the risk and progression of CSVD and VCID.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"6511-6536"},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237459","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":"Cerebrovascular dysregulation and postoperative cognitive alterations after carotid endarterectomy.","authors":"Ágnes Dóra Sándor, Zsófia Czinege, András Szabó, Eszter Losoncz, Krisztina Tóth, Zsuzsanna Mihály, Péter Sótonyi, Béla Merkely, Andrea Székely","doi":"10.1007/s11357-024-01237-6","DOIUrl":"10.1007/s11357-024-01237-6","url":null,"abstract":"<p><p>There are controversial data about the effect of carotid endarterectomy regarding postoperative cognitive function. Our aim was to analyze the effect of cerebral tissue saturation monitored by near-infrared spectroscopy (NIRS) on cognitive function. Perioperative data of 103 asymptomatic patients undergoing elective carotid surgery under general anesthesia were analyzed. Preoperatively and 3 months after the operation, MMSE (Mini Mental State Examination) and MoCA (Montreal Cognitive Assessment) tests were conducted. For cerebral monitoring, NIRS was used, and the lowest rSO₂ value and the degree of desaturation were calculated. Cognitive changes were defined as one standard deviation change from the preoperative test scores, defined as postoperative neurocognitive decline (PNCD) and cognitive improvement (POCI). PNCD was found in 37 patients (35.92%), and POCI was found in 18 patients (17.47%). Female gender, patients with diabetes, and the degree of desaturation were independently associated with PNCD. The degree of desaturation during the cross-clamp period negatively correlated with the change in the MoCA scores (R =  - 0.707, p = 0.001). The 15.5% desaturation ratio had 86.5% sensitivity and 78.8% specificity for discrimination. For POCI, a desaturation of less than 12.65% had 72.2% sensitivity and 67.1% specificity. POCI was associated with lower preoperative MOCA scores and a lower degree of desaturation. We found a significant relation between the change of postoperative cognitive function proven by the MoCA test and cerebral tissue saturation during the clamping period in patients undergoing carotid endarterectomy.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"6301-6315"},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320837","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":"Home-based monitoring of cerebral oxygenation in response to postural changes using near-infrared spectroscopy.","authors":"Marjolein Klop, Jurgen A H R Claassen, Marianne J Floor-Westerdijk, Richard J A van Wezel, Andrea B Maier, Carel G M Meskers","doi":"10.1007/s11357-024-01241-w","DOIUrl":"10.1007/s11357-024-01241-w","url":null,"abstract":"<p><p>Orthostatic hypotension (OH) is prevalent in older adults and can cause falls and hospitalization. Diagnostic intermittent blood pressure (BP) measurements are only a proxy for cerebral perfusion and do not reflect daily-life BP fluctuations. Near-infrared spectroscopy (NIRS)-measured cerebral oxygenation potentially overcomes these drawbacks. This study aimed to determine feasibility, face validity, and reliability of NIRS in the home environment. Ten participants with OH (2 female, mean age 77, SD 3.7) and 11 without OH (5 female, mean age 78, SD 6.7) wore a NIRS sensor at home on two different days for 10-11 h per day. Preceded by a laboratory-situated test, cerebral oxygenation was measured during three standardized supine-stand tests per day and during unsupervised daily life activities. Data availability, quality, and user experience were assessed (feasibility), as well as differences in posture-related oxygenation responses between participants with and without OH and between symptomatic (dizziness, light-headedness, blurred vision) and asymptomatic postural changes (face validity). Reliability was assessed through repetitive supine-stand tests. Up to 80% of the standardized home-based supine-stand tests could be analyzed. Oxygenation recovery values were lower for participants with OH (p = 0 .03-0.15); in those with OH, oxygenation showed a deeper maximum drop for symptomatic than asymptomatic postural changes (p = 0.04). Intra-class correlation coefficients varied from 0.07 to 0.40, with no consistent differences over measurements. This proof-of-concept study shows feasibility and face validity of at-home oxygenation monitoring using NIRS, confirming its potential value for diagnosis and monitoring in OH and OH-related symptoms. Further data are needed for conclusions about reliability.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"6331-6346"},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418547","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":"Systemic metabolic benefits of 17α-estradiol are not exclusively mediated by ERα in glutamatergic or GABAergic neurons.","authors":"Celine Camon, Mel Prescott, Christine Neyt, Caroline Decourt, Michael B Stout, Rebecca E Campbell, Michael Garratt","doi":"10.1007/s11357-024-01192-2","DOIUrl":"10.1007/s11357-024-01192-2","url":null,"abstract":"<p><p>17α-Estradiol (17αE2), a less-feminising enantiomer of 17β-estradiol, has been shown to prolong lifespan and improve metabolic health in a sex-specific manner in male, but not in female mice. Recent studies have demonstrated the pivotal role of estrogen receptor α (ERα) in mediating the effects of 17αE2 on metabolic health. However, the specific tissues and/or neuronal signalling pathways that 17αE2 acts through remain to be elucidated. ERα expression in glutamatergic and GABAergic neurons (principal excitatory and inhibitory neurons respectively) in the hypothalamus is essential for estradiol signalling. Therefore, we hypothesised that knocking out ERα from one of these neuronal populations would attenuate the established beneficial metabolic effects of 17αE2 in male mice exposed to a high fat diet. To test this hypothesis we used two established brain specific ERα KO models, targeting either glutamatergic or GABAergic neurons (Vglut2/Vgat-ERαKO). We show that both of these ERα KO models exhibit a strong reduction in ERα expression in the arcuate nucleus of the hypothalamus, a control centre for metabolic regulation. Deletion of ERα from GABAergic neurons significantly diminished the effect of 17αE2 on body weight relative to controls, although these animals still show metabolic benefits with 17αE2 treatment. The response to 17αE2 was unaffected by ERα deletion in glutamatergic neurons. Our results support a benefit of 17αE2 treatment in protection against metabolic dysfunction, but these effects do not depend on exclusive ERα expression in glutamatergic and GABAergic neurons and persist when ERα expression is strongly reduced in the arcuate nucleus of the hypothalamus.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"6127-6140"},"PeriodicalIF":5.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075622","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}