Miguel Muñoz-Muñoz, Max Weston, Miguel Sierra-Ramón, Bert Bond, Javier Leal-Martín, Owen W Tomlinson, Iván Baltasar-Fernández, María M Morín-Martín, José Losa-Reyna, Julian Alcazar, Francisco José García-García, Ignacio Ara
Mean middle cerebral artery velocity (MCAv) and the pulsatility index (PI), at rest and in response to exercise, are important markers of cerebrovascular health status in middle-aged adults, when vascular decline assumes substantial relevance. Thus, this study aimed to describe and compare the responses of MCAv and PI to incremental exercise. Two hundred and forty-eight volunteers (50–58 years, 55% women) completed a ramp test on a cycle-ergometer. Gas exchange was assessed on a breath-by-breath basis. MCAv was measured via transcranial Doppler and PI calculated. Cardiovascular disease risk (CVR) factors were determined and comprised of measurements of central obesity, blood pressure, fasted plasma glucose, and lipids. The MCAv and PI responses to exercise were compared across body mass index categories, CVR score, and fitness status. We found sex-specific differences in MCAv and PI at rest. However, both sexes showed a similar relative change to baseline (Δ%MCAvmean). Regarding body mass index, obese women (body mass index > 30 kg m−2) had lower MCAv and Δ%MCAvmean and higher PI compared with normo-weight women during exercise. Apart, women with a 0 CVR score showed higher MCAv and lower PI during exercise than those with a score of +3 CVR. Differences between low and high CVR during exercise in Δ%MCAvmean were also found. Eventually, low fitness showed diminished MCAv and a lower response to exercise than high fitness. This study has highlighted significant variability in MCAv responsiveness to exercise among middle-aged adults. Body composition, CVR, and fitness status may play a significant role in preserving cerebrovascular health. These findings shed light on the importance of understanding the cerebrovascular response to exercise.
平均大脑中动脉流速（MCAv）和搏动指数（PI），在休息和运动反应时，是中年人脑血管健康状况的重要标志，当血管衰退具有实质性的相关性时。因此，本研究旨在描述和比较MCAv和PI对增量运动的反应。248名志愿者（50-58岁，其中55%为女性）在自行车测力仪上完成了斜坡测试。气体交换是在每次呼吸的基础上评估的。经颅多普勒测量MCAv，计算PI。心血管疾病风险（CVR）因素由中心肥胖、血压、空腹血糖和血脂测量组成。MCAv和PI对运动的反应在身体质量指数类别、CVR评分和健康状况之间进行比较。我们发现休息时MCAv和PI存在性别特异性差异。然而，两性都显示出与基线相似的相对变化（Δ%MCAvmean）。关于身体质量指数，肥胖女性(身体质量指数&；gt；与正常体重女性相比，30 kg m−2)运动时的MCAv和Δ%MCAvmean较低，PI较高。此外，与CVR得分为+3的女性相比，CVR得分为0的女性在运动期间表现出更高的MCAv和更低的PI。运动时低CVR和高CVR在Δ%MCAvmean上也存在差异。最终，低健康水平表现出较低的MCAv和较低的运动反应。这项研究强调了中年人MCAv对运动反应的显著变异性。身体成分、CVR和健康状况可能在保持脑血管健康中起重要作用。这些发现揭示了理解脑血管对运动反应的重要性。
{"title":"The Influence of Sex, Fitness, BMI, and Cardiovascular Risk Factors on Cerebral Blood Velocity Responsiveness to Graded Exercise Testing in Middle-Aged Adults","authors":"Miguel Muñoz-Muñoz, Max Weston, Miguel Sierra-Ramón, Bert Bond, Javier Leal-Martín, Owen W Tomlinson, Iván Baltasar-Fernández, María M Morín-Martín, José Losa-Reyna, Julian Alcazar, Francisco José García-García, Ignacio Ara","doi":"10.1093/gerona/glae257","DOIUrl":"https://doi.org/10.1093/gerona/glae257","url":null,"abstract":"Mean middle cerebral artery velocity (MCAv) and the pulsatility index (PI), at rest and in response to exercise, are important markers of cerebrovascular health status in middle-aged adults, when vascular decline assumes substantial relevance. Thus, this study aimed to describe and compare the responses of MCAv and PI to incremental exercise. Two hundred and forty-eight volunteers (50–58 years, 55% women) completed a ramp test on a cycle-ergometer. Gas exchange was assessed on a breath-by-breath basis. MCAv was measured via transcranial Doppler and PI calculated. Cardiovascular disease risk (CVR) factors were determined and comprised of measurements of central obesity, blood pressure, fasted plasma glucose, and lipids. The MCAv and PI responses to exercise were compared across body mass index categories, CVR score, and fitness status. We found sex-specific differences in MCAv and PI at rest. However, both sexes showed a similar relative change to baseline (Δ%MCAvmean). Regarding body mass index, obese women (body mass index > 30 kg m−2) had lower MCAv and Δ%MCAvmean and higher PI compared with normo-weight women during exercise. Apart, women with a 0 CVR score showed higher MCAv and lower PI during exercise than those with a score of +3 CVR. Differences between low and high CVR during exercise in Δ%MCAvmean were also found. Eventually, low fitness showed diminished MCAv and a lower response to exercise than high fitness. This study has highlighted significant variability in MCAv responsiveness to exercise among middle-aged adults. Body composition, CVR, and fitness status may play a significant role in preserving cerebrovascular health. These findings shed light on the importance of understanding the cerebrovascular response to exercise.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992572","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}
Background Mitochondrial dysfunction has been demonstrated to be an important hallmark of sarcopenia, yet its specific mechanism remains obscure. In this study, mitochondrial-related genes were used as instrumental variables to proxy for mitochondrial dysfunction, and summary data for sarcopenia-related traits were used as outcomes to examine their genetic association. Methods A total of 1,136 mitochondrial-related genes from the human MitoCarta3.0 database were extracted. Genetic instruments for them were obtained from gene expression quantitative trait locus (eQTLs) study (n = 31,684). Aggregated data for sarcopenia-related traits [(including low hand grip strength (LHGS), appendiceal lean mass (ALM), and usual walking pace (UWP) were provided by large-scale genome-wide association studies (GWASs). We integrated eQTLs data with GWAS data to estimate genetic association between mitochondrial dysfunction and sarcopenia using summary-data-based Mendelian randomization (SMR) analysis. Additionally, we implemented colocalization analysis to strengthen their association. Finally, eQTLs data from skeletomuscular tissue (n = 706) was used to validate the primary findings. Results By integrating the analysis results from the three sarcopenia-related traits, two mitochondrial genes genetically associated with sarcopenia were identified, namely UQCC1 (tier 2 evidence) and ETFDH (tier 3 evidence). Specifically, elevated expression levels of UQCC1 increased LHGS risk (OR = 1.114; 95% CI, 1.078–1.152; P-FDR = 1.70 × 10-7), which matched the negative association between it and UWP (Beta = -0.015; 95% CI, -0.021 – -0.010; P-FDR = 6.70 × 10-5). Furthermore, elevated expression levels of ETFDH were found to be associated with both lower ALM (Beta = 0.031; 95% CI, 0.020–0.042; P-FDR = 1.41 × 10-6) and UWP (Beta = 0.013; 95% CI, 0.006–0.021; P-FDR = 0.029). Of note, consistent results were replicated in specific skeletomuscular tissues, further suggesting our findings were robust. Conclusions Our analyses revealed the genetic association between two mitochondrial-related genes, i.e., UQCC1 and ETFDH, and sarcopenia, highlighting the pivotal role of mitochondrial dysfunction driven by these genes in the pathogenesis of sarcopenia. Importantly, these candidate genes represent potential clinical drug targets for the treatment of sarcopenia.
{"title":"Identification of association between mitochondrial dysfunction and sarcopenia using summary-data-based Mendelian randomization and colocalization analyses","authors":"Jiale Xie, Jinrong Hao, Xin Xu, Jiachen Wang, Dinglong Yang, Hui Yu, Junfei Guo, Mingyi Yang, Peng Xu","doi":"10.1093/gerona/glaf006","DOIUrl":"https://doi.org/10.1093/gerona/glaf006","url":null,"abstract":"Background Mitochondrial dysfunction has been demonstrated to be an important hallmark of sarcopenia, yet its specific mechanism remains obscure. In this study, mitochondrial-related genes were used as instrumental variables to proxy for mitochondrial dysfunction, and summary data for sarcopenia-related traits were used as outcomes to examine their genetic association. Methods A total of 1,136 mitochondrial-related genes from the human MitoCarta3.0 database were extracted. Genetic instruments for them were obtained from gene expression quantitative trait locus (eQTLs) study (n = 31,684). Aggregated data for sarcopenia-related traits [(including low hand grip strength (LHGS), appendiceal lean mass (ALM), and usual walking pace (UWP) were provided by large-scale genome-wide association studies (GWASs). We integrated eQTLs data with GWAS data to estimate genetic association between mitochondrial dysfunction and sarcopenia using summary-data-based Mendelian randomization (SMR) analysis. Additionally, we implemented colocalization analysis to strengthen their association. Finally, eQTLs data from skeletomuscular tissue (n = 706) was used to validate the primary findings. Results By integrating the analysis results from the three sarcopenia-related traits, two mitochondrial genes genetically associated with sarcopenia were identified, namely UQCC1 (tier 2 evidence) and ETFDH (tier 3 evidence). Specifically, elevated expression levels of UQCC1 increased LHGS risk (OR = 1.114; 95% CI, 1.078–1.152; P-FDR = 1.70 × 10-7), which matched the negative association between it and UWP (Beta = -0.015; 95% CI, -0.021 – -0.010; P-FDR = 6.70 × 10-5). Furthermore, elevated expression levels of ETFDH were found to be associated with both lower ALM (Beta = 0.031; 95% CI, 0.020–0.042; P-FDR = 1.41 × 10-6) and UWP (Beta = 0.013; 95% CI, 0.006–0.021; P-FDR = 0.029). Of note, consistent results were replicated in specific skeletomuscular tissues, further suggesting our findings were robust. Conclusions Our analyses revealed the genetic association between two mitochondrial-related genes, i.e., UQCC1 and ETFDH, and sarcopenia, highlighting the pivotal role of mitochondrial dysfunction driven by these genes in the pathogenesis of sarcopenia. Importantly, these candidate genes represent potential clinical drug targets for the treatment of sarcopenia.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988536","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}
Tatiana Guncay, Jorge Concha, Pedro Lobos, Jamileth More, Barbara Bruna, Daniel Sansores, Pamela Contreras, Daniela P Ponce, Julian Brañez, Gabriel Quiroz, Genaro Barrientos, Cecilia Hidalgo, Felipe Salech
Postoperative delirium (POD), an acute cognitive dysfunction linked to morbidity and mortality, is characterized by memory impairments and disturbances in consciousness, particularly in patients aged 65 and older. Neuroinflammation and NAD+ imbalance are key mechanisms behind POD, leading to synaptic and cognitive deterioration. However, how surgery contributes to POD and neuroinflammation remains unclear, and effective treatments are lacking. Here we used a rodent model of bone fracture to examine the impact of surgery on synaptic plasticity, inflammation, and cognition. Additionally, we explored whether treatment with Nicotinamide (NAM), a NAD+ precursor, reduced the neuroinflammation and metabolic imbalance caused by surgery. Female C57BL/6J mice aged 20-22 months underwent tibial fracture surgery and received pre- and post-surgery NAM treatment. Neuroinflammation, synaptic plasticity, and cognition were assessed 72 hours post-surgery via long-term potentiation (LTP) assays, dendritic spine counting, and behavioral tests (open field maze and Y-maze). Tibial fracture surgery decreased LTP, dendritic spine density, and hippocampal-dependent memory function, and increased hippocampal inflammatory markers (IL-1 beta mRNA, CD38, and SIRT1 protein content); NAM pretreatment prevented these changes. Given surgery adverse effects on LTP and dendritic spine density, we assessed cellular oxidative state and BDNF protein levels. We found that surgery increased the oxidation of ryanodine receptor calcium channels (cellular redox sensors), and decreased BDNF protein levels; NAM supplementation mitigated both effects and prevented the cognitive decline and synaptic plasticity deficits while reducing inflammation post-surgery by lowering IL-1 beta and CD38 protein levels. We propose that the CD38 signaling pathway mediates these NAM protective effects.
{"title":"Nicotinamide Prevents The Plasticity Impairments And The Cognitive Dysfunction Caused By Bone Fracture In Older Mice","authors":"Tatiana Guncay, Jorge Concha, Pedro Lobos, Jamileth More, Barbara Bruna, Daniel Sansores, Pamela Contreras, Daniela P Ponce, Julian Brañez, Gabriel Quiroz, Genaro Barrientos, Cecilia Hidalgo, Felipe Salech","doi":"10.1093/gerona/glae303","DOIUrl":"https://doi.org/10.1093/gerona/glae303","url":null,"abstract":"Postoperative delirium (POD), an acute cognitive dysfunction linked to morbidity and mortality, is characterized by memory impairments and disturbances in consciousness, particularly in patients aged 65 and older. Neuroinflammation and NAD+ imbalance are key mechanisms behind POD, leading to synaptic and cognitive deterioration. However, how surgery contributes to POD and neuroinflammation remains unclear, and effective treatments are lacking. Here we used a rodent model of bone fracture to examine the impact of surgery on synaptic plasticity, inflammation, and cognition. Additionally, we explored whether treatment with Nicotinamide (NAM), a NAD+ precursor, reduced the neuroinflammation and metabolic imbalance caused by surgery. Female C57BL/6J mice aged 20-22 months underwent tibial fracture surgery and received pre- and post-surgery NAM treatment. Neuroinflammation, synaptic plasticity, and cognition were assessed 72 hours post-surgery via long-term potentiation (LTP) assays, dendritic spine counting, and behavioral tests (open field maze and Y-maze). Tibial fracture surgery decreased LTP, dendritic spine density, and hippocampal-dependent memory function, and increased hippocampal inflammatory markers (IL-1 beta mRNA, CD38, and SIRT1 protein content); NAM pretreatment prevented these changes. Given surgery adverse effects on LTP and dendritic spine density, we assessed cellular oxidative state and BDNF protein levels. We found that surgery increased the oxidation of ryanodine receptor calcium channels (cellular redox sensors), and decreased BDNF protein levels; NAM supplementation mitigated both effects and prevented the cognitive decline and synaptic plasticity deficits while reducing inflammation post-surgery by lowering IL-1 beta and CD38 protein levels. We propose that the CD38 signaling pathway mediates these NAM protective effects.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988539","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}
Thomas M Gill, Jingchen Liang, Brent Vander Wyk, Linda Leo-Summers, Yi Wang, Robert D Becher, Kendra Davis-Plourde
Background In longitudinal studies of older persons, complete ascertainment of mortality is needed to minimize potential biases. To ascertain mortality in the National Health and Aging Trends Study (NHATS), investigators are advised to use its Sensitive files, which include month and year of death on most decedents who had not dropped out of the study. Because losses to follow-up are not insubstantial, ascertainment of mortality is likely incomplete. Methods We used linked Medicare data as the reference standard to determine the extent by which mortality is underestimated in NHATS through use of its recommended strategy. Ascertainment of mortality was compared between the two strategies over 10 years for 7,608 members of the 2011 cohort and 5 years for 7,498 members of the 2015 cohort. Results The Sensitive files did not identify a large number of decedents, leading to suboptimal sensitivity, ranging from 61.3% (2011 cohort, 10 years) to 75.5% (2015 cohort, 5 years). Some non-decedents were also misclassified as dead using the Sensitive files. Cumulative mortality rates were modestly lower for the recommended strategy, although the number of participants at risk decreased markedly over time. Mortality incidence rates were also modestly lower for the recommended strategy, with incidence rate ratios ranging from 0.88 (2011 cohort, 10 years) to 0.94 (2011 cohort, 5 years). Conclusions The strategy recommended by NHATS leads to incomplete ascertainment and, to a lesser degree, misclassification of mortality. Caution may be warranted when interpreting results of longitudinal analyses in NHATS that evaluate mortality using the recommended strategy.
{"title":"Incomplete Ascertainment of Mortality in a Nationally Representative Longitudinal Study of Community-Living Older Americans","authors":"Thomas M Gill, Jingchen Liang, Brent Vander Wyk, Linda Leo-Summers, Yi Wang, Robert D Becher, Kendra Davis-Plourde","doi":"10.1093/gerona/glaf014","DOIUrl":"https://doi.org/10.1093/gerona/glaf014","url":null,"abstract":"Background In longitudinal studies of older persons, complete ascertainment of mortality is needed to minimize potential biases. To ascertain mortality in the National Health and Aging Trends Study (NHATS), investigators are advised to use its Sensitive files, which include month and year of death on most decedents who had not dropped out of the study. Because losses to follow-up are not insubstantial, ascertainment of mortality is likely incomplete. Methods We used linked Medicare data as the reference standard to determine the extent by which mortality is underestimated in NHATS through use of its recommended strategy. Ascertainment of mortality was compared between the two strategies over 10 years for 7,608 members of the 2011 cohort and 5 years for 7,498 members of the 2015 cohort. Results The Sensitive files did not identify a large number of decedents, leading to suboptimal sensitivity, ranging from 61.3% (2011 cohort, 10 years) to 75.5% (2015 cohort, 5 years). Some non-decedents were also misclassified as dead using the Sensitive files. Cumulative mortality rates were modestly lower for the recommended strategy, although the number of participants at risk decreased markedly over time. Mortality incidence rates were also modestly lower for the recommended strategy, with incidence rate ratios ranging from 0.88 (2011 cohort, 10 years) to 0.94 (2011 cohort, 5 years). Conclusions The strategy recommended by NHATS leads to incomplete ascertainment and, to a lesser degree, misclassification of mortality. Caution may be warranted when interpreting results of longitudinal analyses in NHATS that evaluate mortality using the recommended strategy.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988537","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}
Tariq Faquih, Astrid van Hylckama Vlieg, Praveen Surendran, Adam S Butterworth, Ruifang Li-Gao, Renée de Mutsert, Frits R Rosendaal, Raymond Noordam, Diana van Heemst, Ko Willems van Dijk, Dennis O Mook-Kanamori
Chronological age is a major risk factor for numerous diseases. However, chronological age does not capture the complex biological aging process. the difference between the chronological age and biologically driven aging could be more informative in reflecting health status. Here, we set out to develop a metabolomic age prediction model by applying ridge regression and bootstrapping with 826 metabolites (678 endogenous and 148 xenobiotics) measured by an untargeted platform in relatively healthy blood donors aged 18-75 years from the INTERVAL study (N=11,977;50.2% men). After bootstrapping internal validation, the metabolomic age prediction models demonstrated high performance with an adjusted R2 of 0.83 using all metabolites and 0.82 using only endogenous metabolites. The former was significantly associated with obesity and cardiovascular disease (CVD) in the NEO study (N=599;47.0% men; age range=45-65) due to the contribution of medication derived metabolites—namely salicylate and ibuprofen—and environmental exposures such as cotinine. Additional metabolomic age prediction models using all metabolites were developed for men and women separately. The models had high performance (R²=0.85 and 0.86) but shared a moderate correlation of 0.72. Furthermore, we observed 163 sex-dimorphic metabolites, including threonine, glycine, cholesterol, and androgenic and progesterone-related metabolites. Our strongest predictors across all models were novel and included hydroxyasparagine (Model Endo+Xeno β=4.74), vanillylmandelate (β=4.07), and 5,6-dihydrouridine (β=-4.2). Our study presents a robust metabolomic age model that reveals distinct sex-based age-related metabolic patterns and illustrates the value of including xenobiotic to enhance metabolomic prediction accuracy.
{"title":"Robust metabolomic age prediction based on a wide selection of metabolites","authors":"Tariq Faquih, Astrid van Hylckama Vlieg, Praveen Surendran, Adam S Butterworth, Ruifang Li-Gao, Renée de Mutsert, Frits R Rosendaal, Raymond Noordam, Diana van Heemst, Ko Willems van Dijk, Dennis O Mook-Kanamori","doi":"10.1093/gerona/glae280","DOIUrl":"https://doi.org/10.1093/gerona/glae280","url":null,"abstract":"Chronological age is a major risk factor for numerous diseases. However, chronological age does not capture the complex biological aging process. the difference between the chronological age and biologically driven aging could be more informative in reflecting health status. Here, we set out to develop a metabolomic age prediction model by applying ridge regression and bootstrapping with 826 metabolites (678 endogenous and 148 xenobiotics) measured by an untargeted platform in relatively healthy blood donors aged 18-75 years from the INTERVAL study (N=11,977;50.2% men). After bootstrapping internal validation, the metabolomic age prediction models demonstrated high performance with an adjusted R2 of 0.83 using all metabolites and 0.82 using only endogenous metabolites. The former was significantly associated with obesity and cardiovascular disease (CVD) in the NEO study (N=599;47.0% men; age range=45-65) due to the contribution of medication derived metabolites—namely salicylate and ibuprofen—and environmental exposures such as cotinine. Additional metabolomic age prediction models using all metabolites were developed for men and women separately. The models had high performance (R²=0.85 and 0.86) but shared a moderate correlation of 0.72. Furthermore, we observed 163 sex-dimorphic metabolites, including threonine, glycine, cholesterol, and androgenic and progesterone-related metabolites. Our strongest predictors across all models were novel and included hydroxyasparagine (Model Endo+Xeno β=4.74), vanillylmandelate (β=4.07), and 5,6-dihydrouridine (β=-4.2). Our study presents a robust metabolomic age model that reveals distinct sex-based age-related metabolic patterns and illustrates the value of including xenobiotic to enhance metabolomic prediction accuracy.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987532","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}
Eleanor Gallagher, Amanda Lavan, Rose Anne Kenny, Robert Briggs
Background It has been suggested that dog walking may protect against falls and mobility problems in later life, but little work to date has examined this. The aim of this study was to assess if regular dog walking was associated with reduced likelihood of falls, fear of falling and mobility problems in a large cohort of community-dwelling older people. Methods Participants ≥60 years at Wave 5 of The Irish Longitudinal Study on Ageing were included. Regular dog walking was ≥4 days/week by self-report. The control group consisted of participants who did not own a dog or who did not regularly walk their dog. Falls and fear of falling were by self-report. Mobility was measured with Timed-Up-and-Go (TUG). Logistic Regression models assessed associations between regular dog walking and outcomes of interest. Results Regular dog walkers (629/4,161, 15%) had a significantly faster TUG (10.3 (10.1-10.5) vs 11.7 (11.1-12.2) seconds, t=2.11, p=0.0343) and lower likelihood of unexplained falls (OR 0.60 (0.38–0.96; p=0.034), fear of falling (OR 0.79 (95% CI 0.64–0.98); p=0.032) and mobility problems (0.64 (0.45–0.91); p=0.015) in fully-adjusted models. Regular dog walking was also associated with a significantly lower likelihood of fear of falling (OR 0.79 (95% CI 0.64–0.98); p = 0.032). Discussion This study demonstrates a significantly lower prevalence of mobility impairment, falls and fear of falling amongst community-dwelling older people who regularly walk their dog. While longitudinal and dedicated studies are required, older people should be encouraged to continue regular dog walking where feasible, as it may help in maintaining mobility and reducing falls.
有人认为遛狗可以预防跌倒和晚年行动不便，但迄今为止很少有研究对此进行研究。这项研究的目的是评估定期遛狗是否与减少跌倒、害怕跌倒和行动不便的可能性有关，研究对象是一大批居住在社区的老年人。方法纳入爱尔兰老龄化纵向研究第5期≥60岁的参与者。自述定期遛狗≥4天/周。对照组由没有养狗或不经常遛狗的参与者组成。跌倒和害怕跌倒都是自我报告。移动性用time - up -and- go （TUG）测量。逻辑回归模型评估了定期遛狗与感兴趣的结果之间的关系。结果常规遛狗者（629/4,161,15%）的TUG速度显著加快(10.3 (10.1-10.5)vs 11.7（11.1-12.2）秒，t=2.11, p=0.0343)，不明原因跌倒的可能性较低(OR 0.60 (0.38-0.96；p=0.034)，害怕跌倒(OR 0.79 (95% CI 0.64-0.98)；P =0.032)和活动能力问题(0.64 (0.45-0.91)；P =0.015)。经常遛狗也与害怕摔倒的可能性显著降低相关(OR 0.79 (95% CI 0.64-0.98)；P = 0.032)。这项研究表明，在经常遛狗的社区老年人中，行动障碍、跌倒和害怕跌倒的患病率明显较低。虽然需要进行纵向和专门的研究，但应鼓励老年人在可行的情况下继续定期遛狗，因为这可能有助于保持活动能力并减少跌倒。
{"title":"The Association of Regular Dog Walking with Mobility, Falls and Fear of Falling in Later Life","authors":"Eleanor Gallagher, Amanda Lavan, Rose Anne Kenny, Robert Briggs","doi":"10.1093/gerona/glaf010","DOIUrl":"https://doi.org/10.1093/gerona/glaf010","url":null,"abstract":"Background It has been suggested that dog walking may protect against falls and mobility problems in later life, but little work to date has examined this. The aim of this study was to assess if regular dog walking was associated with reduced likelihood of falls, fear of falling and mobility problems in a large cohort of community-dwelling older people. Methods Participants ≥60 years at Wave 5 of The Irish Longitudinal Study on Ageing were included. Regular dog walking was ≥4 days/week by self-report. The control group consisted of participants who did not own a dog or who did not regularly walk their dog. Falls and fear of falling were by self-report. Mobility was measured with Timed-Up-and-Go (TUG). Logistic Regression models assessed associations between regular dog walking and outcomes of interest. Results Regular dog walkers (629/4,161, 15%) had a significantly faster TUG (10.3 (10.1-10.5) vs 11.7 (11.1-12.2) seconds, t=2.11, p=0.0343) and lower likelihood of unexplained falls (OR 0.60 (0.38–0.96; p=0.034), fear of falling (OR 0.79 (95% CI 0.64–0.98); p=0.032) and mobility problems (0.64 (0.45–0.91); p=0.015) in fully-adjusted models. Regular dog walking was also associated with a significantly lower likelihood of fear of falling (OR 0.79 (95% CI 0.64–0.98); p = 0.032). Discussion This study demonstrates a significantly lower prevalence of mobility impairment, falls and fear of falling amongst community-dwelling older people who regularly walk their dog. While longitudinal and dedicated studies are required, older people should be encouraged to continue regular dog walking where feasible, as it may help in maintaining mobility and reducing falls.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962808","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}
s Background Glucagon-like peptide-1 receptor agonists (GLP1RAs) are widely used in manageing type 2 diabetes mellitus and weight control. Their potential in treating ageing-related diseases has been gaining attention in recent years. However, the long-term effects of GLP1RAs on these diseases have yet to be fully revealed. Methods Using genetic variant in the GLP1R gene to model the long-term effects of GLP1RAs, this Mendelian randomization (MR) study systematically explored potential causal associations between GLP1R agonism and 12 ageing-related diseases and indicators. Genetic summary datasets used in this study were obtained from previous genome-wide association studies. Results The primary MR analysis results suggested that GLP1R agonism was potentially positively causally associated with appendicular lean mass (Beta = 0.246, 95% CI = 0.096 - 0.396), whole body fat-free mass (Beta = 0.202, 95% CI = 0.048 - 0.355), and lung function (FVC) (Beta = 0.179, 95% CI = 0.152 - 0.205) (p < 0.05). Additionally, a potential negative causal association was observed with myocardial infarction (OR = 0.430, 95% CI = 0.249 - 0.745) (p < 0.05). Conclusion The present MR study provides exploratory evidence suggesting potential causal associations between GLP1R agonism and appendicular lean mass, whole-body fat-free mass, lung function (FVC), and myocardial infarction. Given the exploratory nature of these findings and the limitations of the MR methodology, further research is needed to validate these results and investigate the underlying biological mechanisms.
胰高血糖素样肽-1受体激动剂（GLP1RAs）广泛用于治疗2型糖尿病和控制体重。近年来，它们在治疗与衰老有关的疾病方面的潜力受到了人们的关注。然而，GLP1RAs对这些疾病的长期影响尚未完全揭示。方法利用GLP1R基因的遗传变异来模拟GLP1RAs的长期影响，这项孟德尔随机化（MR）研究系统地探索了GLP1R激动作用与12种衰老相关疾病和指标之间的潜在因果关系。本研究中使用的遗传汇总数据集来自先前的全基因组关联研究。结果初步MR分析结果显示，GLP1R受体兴奋性与阑尾瘦质量（Beta = 0.246, 95% CI = 0.096 ~ 0.396）、全身无脂质量（Beta = 0.202, 95% CI = 0.048 ~ 0.355）和肺功能（FVC） （Beta = 0.179, 95% CI = 0.152 ~ 0.205）呈潜在正相关(p <；0.05)。此外，观察到心肌梗死与潜在的负相关因果关系（OR = 0.430, 95% CI = 0.249 - 0.745） (p <；0.05)。结论本MR研究提供了探索性证据，提示GLP1R激动作用与阑尾瘦质量、全身无脂质量、肺功能（FVC）和心肌梗死之间存在潜在的因果关系。鉴于这些发现的探索性和MR方法的局限性，需要进一步的研究来验证这些结果并调查潜在的生物学机制。
{"title":"Exploring the Potential Effect of GLP1R Agonism on Common Ageing-Related Diseases via Glucose Reduction: A Mendelian Randomization Study","authors":"Wei Jiang, Kaixi Ding, Maoyi Yang, Zhipeng Hu, Rensong Yue","doi":"10.1093/gerona/glaf007","DOIUrl":"https://doi.org/10.1093/gerona/glaf007","url":null,"abstract":"s Background Glucagon-like peptide-1 receptor agonists (GLP1RAs) are widely used in manageing type 2 diabetes mellitus and weight control. Their potential in treating ageing-related diseases has been gaining attention in recent years. However, the long-term effects of GLP1RAs on these diseases have yet to be fully revealed. Methods Using genetic variant in the GLP1R gene to model the long-term effects of GLP1RAs, this Mendelian randomization (MR) study systematically explored potential causal associations between GLP1R agonism and 12 ageing-related diseases and indicators. Genetic summary datasets used in this study were obtained from previous genome-wide association studies. Results The primary MR analysis results suggested that GLP1R agonism was potentially positively causally associated with appendicular lean mass (Beta = 0.246, 95% CI = 0.096 - 0.396), whole body fat-free mass (Beta = 0.202, 95% CI = 0.048 - 0.355), and lung function (FVC) (Beta = 0.179, 95% CI = 0.152 - 0.205) (p &lt; 0.05). Additionally, a potential negative causal association was observed with myocardial infarction (OR = 0.430, 95% CI = 0.249 - 0.745) (p &lt; 0.05). Conclusion The present MR study provides exploratory evidence suggesting potential causal associations between GLP1R agonism and appendicular lean mass, whole-body fat-free mass, lung function (FVC), and myocardial infarction. Given the exploratory nature of these findings and the limitations of the MR methodology, further research is needed to validate these results and investigate the underlying biological mechanisms.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"013 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962791","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}
Taylor McClennen, Hari Sharma, Douglas P Kiel, Richard H Fortinsky, Camelia P Guild, Denise Orwig, Jay Magaziner, Ellen F Binder, Sarah D Berry
Background High psychological resilience is associated with improved functional outcomes for older adults recovering from hip fracture. The objective of this study was to identify factors associated with increased psychological resilience in older women after hip fracture. Methods 129 women aged ≥65 years with recent surgically-repaired hip fracture were enrolled in a trial of exercise and testosterone therapy. The Brief Resilience Scale (BRS) measured baseline resilience, and was categorized as low (BRS<4) or high (BRS≥4). Sociodemographic (e.g., education), medical, and neuropsychological factors (e.g., cognition by Short Blessed Test, mental health by a Global Mental Health Score (PROMIS-GMH), and depressive symptoms by Geriatric Depression Score (GDS)) were considered as independent variables. Individual factors were evaluated for their association with resilience using bivariate regression, and those having a significance level of p≤0.10 were entered into age-adjusted multivariate logistic regression models. Results 57 women (44%) reported high resilience. Neither education nor cognition was significantly associated with resilience. Lower GDS and better PROMIS-GMH scores were associated with high resilience in adjusted models. For every one-point worsening in GDS, the adjusted odds ratio (AOR) for high vs. low resilience was 0.76 (95% CI 0.61,0.93). In a model with GDS, PROMIS-GMH, and age, positive mental health remained significantly associated with higher resilience (AOR 1.34, 95% CI 1.14,1.58). Conclusions In older women after hip fracture, fewer depressive symptoms and better mental health were associated with higher psychological resilience. Addressing overall mental health when recovering from hip fracture could contribute to increasing psychological resilience thereby maximizing recovery potential.
背景：高心理弹性与老年人髋部骨折后功能恢复的改善有关。本研究的目的是确定老年女性髋部骨折后心理恢复能力增强的相关因素。方法对129例年龄≥65岁近期手术修复髋部骨折的女性进行运动和睾酮治疗试验。简要弹性量表（BRS）测量基线弹性，分为低（BRS<4）和高（BRS≥4）。社会人口学（如教育）、医学和神经心理因素（如Short Blessed Test的认知、全球心理健康评分（promisi - gmh）的心理健康和老年抑郁评分（GDS）的抑郁症状）被视为独立变量。采用双变量回归评估个体因素与心理弹性的相关性，p≤0.10的显著性水平进入年龄调整后的多变量logistic回归模型。结果57名女性（44%）报告了高弹性。教育和认知都与恢复力无关。在调整后的模型中，较低的GDS和较好的promise - gmh得分与高弹性相关。GDS每恶化1点，高恢复力与低恢复力的调整优势比（AOR）为0.76 （95% CI 0.61,0.93）。在GDS、promise - gmh和年龄的模型中，积极的心理健康仍然与更高的恢复力显著相关（AOR 1.34, 95% CI 1.14,1.58）。结论老年女性髋部骨折后抑郁症状较少，心理健康状况较好，心理弹性较高。从髋部骨折中恢复时解决整体心理健康问题有助于提高心理弹性，从而最大限度地提高恢复潜力。
{"title":"Better mental health and fewer depressive symptoms are associated with greater psychological resilience after hip fracture","authors":"Taylor McClennen, Hari Sharma, Douglas P Kiel, Richard H Fortinsky, Camelia P Guild, Denise Orwig, Jay Magaziner, Ellen F Binder, Sarah D Berry","doi":"10.1093/gerona/glaf008","DOIUrl":"https://doi.org/10.1093/gerona/glaf008","url":null,"abstract":"Background High psychological resilience is associated with improved functional outcomes for older adults recovering from hip fracture. The objective of this study was to identify factors associated with increased psychological resilience in older women after hip fracture. Methods 129 women aged ≥65 years with recent surgically-repaired hip fracture were enrolled in a trial of exercise and testosterone therapy. The Brief Resilience Scale (BRS) measured baseline resilience, and was categorized as low (BRS&lt;4) or high (BRS≥4). Sociodemographic (e.g., education), medical, and neuropsychological factors (e.g., cognition by Short Blessed Test, mental health by a Global Mental Health Score (PROMIS-GMH), and depressive symptoms by Geriatric Depression Score (GDS)) were considered as independent variables. Individual factors were evaluated for their association with resilience using bivariate regression, and those having a significance level of p≤0.10 were entered into age-adjusted multivariate logistic regression models. Results 57 women (44%) reported high resilience. Neither education nor cognition was significantly associated with resilience. Lower GDS and better PROMIS-GMH scores were associated with high resilience in adjusted models. For every one-point worsening in GDS, the adjusted odds ratio (AOR) for high vs. low resilience was 0.76 (95% CI 0.61,0.93). In a model with GDS, PROMIS-GMH, and age, positive mental health remained significantly associated with higher resilience (AOR 1.34, 95% CI 1.14,1.58). Conclusions In older women after hip fracture, fewer depressive symptoms and better mental health were associated with higher psychological resilience. Addressing overall mental health when recovering from hip fracture could contribute to increasing psychological resilience thereby maximizing recovery potential.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937062","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}
Eric Tsz-Chun Lai, Irene Yuk-Ying Ho, Hung Chak Ho, Pui-Hing Chau, Terry Cheuk-Fung Yip, Grace Lai-Hung Wong, Jean Woo
Background The older population is more vulnerable to the impact of extreme hot weather events (EHWEs), while the impact on the frailer institutionalised older population was seldom assessed. Our objective was to assess the relationship between EHWEs and hospitalisation risks among institutionalised and community-dwelling older people. Methods We used territory-wide hospitalisation record of Hong Kong from year 2012 to 2018 to assess the associations between EHWEs and cardiovascular and respiratory disease hospitalisations in the population aged 65 or above. A very hot day (VHD) was defined as the daily maximum temperature ≥ 33°C, and a hot night (HN) was defined as the daily minimum temperature ≥ 28°C. We assessed whether prolonged exposure to high temperatures (defined as 3 consecutive VHDs (3VHD) or HNs (3HN)) was related to higher risk of hospitalisation over a lag period of 0-21 days. Time-stratified case-crossover design was used. Analyses were stratified by old age home (OAH) residence status. Results Exposure to 3VHDs was related to higher risk of cardiovascular disease admissions for community-dwelling older people [relative risk (RR): 1.09; 95% confidence interval (95%CI): 1.03 to 1.14 (lagged 4 days, i.e. delayed manifestation up to 4 days)] while for OAH residents, the association could have a lag of 18 days (RR: 1.28; 95%CI 1.05 to 1.54). For respiratory disease admissions, such relatively long delayed relationship was not clearly observed. Conclusions The warming climate could increase healthcare demand in the long run. Frailer patients could present with a generally more marked and delayed onset of cardiovascular disease aggravation than the community-dwelling population.
{"title":"Extreme hot weather events and risk of hospitalisation for cardiovascular and respiratory diseases in older people in Hong Kong in 2012 to 2018","authors":"Eric Tsz-Chun Lai, Irene Yuk-Ying Ho, Hung Chak Ho, Pui-Hing Chau, Terry Cheuk-Fung Yip, Grace Lai-Hung Wong, Jean Woo","doi":"10.1093/gerona/glaf002","DOIUrl":"https://doi.org/10.1093/gerona/glaf002","url":null,"abstract":"Background The older population is more vulnerable to the impact of extreme hot weather events (EHWEs), while the impact on the frailer institutionalised older population was seldom assessed. Our objective was to assess the relationship between EHWEs and hospitalisation risks among institutionalised and community-dwelling older people. Methods We used territory-wide hospitalisation record of Hong Kong from year 2012 to 2018 to assess the associations between EHWEs and cardiovascular and respiratory disease hospitalisations in the population aged 65 or above. A very hot day (VHD) was defined as the daily maximum temperature ≥ 33°C, and a hot night (HN) was defined as the daily minimum temperature ≥ 28°C. We assessed whether prolonged exposure to high temperatures (defined as 3 consecutive VHDs (3VHD) or HNs (3HN)) was related to higher risk of hospitalisation over a lag period of 0-21 days. Time-stratified case-crossover design was used. Analyses were stratified by old age home (OAH) residence status. Results Exposure to 3VHDs was related to higher risk of cardiovascular disease admissions for community-dwelling older people [relative risk (RR): 1.09; 95% confidence interval (95%CI): 1.03 to 1.14 (lagged 4 days, i.e. delayed manifestation up to 4 days)] while for OAH residents, the association could have a lag of 18 days (RR: 1.28; 95%CI 1.05 to 1.54). For respiratory disease admissions, such relatively long delayed relationship was not clearly observed. Conclusions The warming climate could increase healthcare demand in the long run. Frailer patients could present with a generally more marked and delayed onset of cardiovascular disease aggravation than the community-dwelling population.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935939","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}
Ribosome-associated quality control (RQC), a ubiquitous process essential for maintaining protein homeostasis in eukaryotes, acts as a critical surveillance system for protein translation. By identifying and eliminating stalled ribosomes, RQC prevents aberrant translation and the production of potentially toxic misfolded proteins. The review focuses on the role of RQC in mammals, where its complete functionality remains to be elucidated. This study delves into the mechanisms through which dysfunction in RQC plays a role in the development of neurological disorders, focusing on neurodegenerative and neurodevelopmental diseases. We explore the underlying mechanisms by which RQC dysfunction contributes to the pathogenesis of neurological disorders, particularly neurodegenerative and neurodevelopmental diseases. Further research is crucial to unravel the intricate mechanisms governing RQC's influence on neurological function. This knowledge will pave the way for exploring therapeutic avenues targeting RQC factors as potential interventions for these debilitating diseases. By shedding light on RQC's contribution to neurological disorders, this review opens doors for developing targeted therapies and interventions.
{"title":"The relationship between Ribosome-associated Quality Control and neurological disorders","authors":"Juan Wang, Jianhua Wang, Hanshuai Cao, Yingming Xing, Zhuoran Wang, Jing Ma, Rongjuan Zhao, Wei Zhang, Junhong Guo, Xueli Chang","doi":"10.1093/gerona/glae304","DOIUrl":"https://doi.org/10.1093/gerona/glae304","url":null,"abstract":"Ribosome-associated quality control (RQC), a ubiquitous process essential for maintaining protein homeostasis in eukaryotes, acts as a critical surveillance system for protein translation. By identifying and eliminating stalled ribosomes, RQC prevents aberrant translation and the production of potentially toxic misfolded proteins. The review focuses on the role of RQC in mammals, where its complete functionality remains to be elucidated. This study delves into the mechanisms through which dysfunction in RQC plays a role in the development of neurological disorders, focusing on neurodegenerative and neurodevelopmental diseases. We explore the underlying mechanisms by which RQC dysfunction contributes to the pathogenesis of neurological disorders, particularly neurodegenerative and neurodevelopmental diseases. Further research is crucial to unravel the intricate mechanisms governing RQC's influence on neurological function. This knowledge will pave the way for exploring therapeutic avenues targeting RQC factors as potential interventions for these debilitating diseases. By shedding light on RQC's contribution to neurological disorders, this review opens doors for developing targeted therapies and interventions.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884135","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：