The age-related loss of muscle mass is partly driven by a reduction in serial sarcomere number (SSN), and further SSN loss occurs during immobilization. SSN is associated with optimal force and power production and muscle passive tension, thus immobilization-induced SSN loss is especially a concern for older individuals who are often subjected to forced muscle disuse with illness and injury. We previously showed that submaximal eccentric resistance training increased SSN and improved muscle function in old rats. The present study investigated whether this training could prevent the losses of SSN and function when performed intermittently during immobilization. 10 old (32 months) and 10 young (8 months) rats underwent unilateral casting of the plantar flexors in a shortened position for 2 weeks. Thrice weekly, casts were removed for isokinetic eccentric resistance training. Pre- and post-training we assessed in-vivo maximum isometric torque at ankle angles corresponding to stretched and neutral muscle lengths, the passive torque-angle relationship, and isotonic power. The soleus and medial gastrocnemius were harvested for SSN measurements, with the untrained leg as a control. In old and young rats, muscles of the casted leg had smaller muscle wet weights (20-40%), physiological cross-sectional area (16-20%), and SSN (7-29%) than the control leg. Furthermore, maximum isometric torque (37-46%) and isotonic power (≈70%) decreased, and passive torque increased (+≈400%) from pre- to post-training for both age groups. Thus, irrespective of age, submaximal eccentric resistance training 3 days/week was ineffective for preventing the losses of muscle contractile tissue and mechanical function during casting.
{"title":"Submaximal eccentric training during immobilization does not prevent serial sarcomere loss or impairments in mechanical function in old or young rats","authors":"Avery Hinks, Ethan Vlemmix, Geoffrey A Power","doi":"10.1093/gerona/glaf082","DOIUrl":"https://doi.org/10.1093/gerona/glaf082","url":null,"abstract":"The age-related loss of muscle mass is partly driven by a reduction in serial sarcomere number (SSN), and further SSN loss occurs during immobilization. SSN is associated with optimal force and power production and muscle passive tension, thus immobilization-induced SSN loss is especially a concern for older individuals who are often subjected to forced muscle disuse with illness and injury. We previously showed that submaximal eccentric resistance training increased SSN and improved muscle function in old rats. The present study investigated whether this training could prevent the losses of SSN and function when performed intermittently during immobilization. 10 old (32 months) and 10 young (8 months) rats underwent unilateral casting of the plantar flexors in a shortened position for 2 weeks. Thrice weekly, casts were removed for isokinetic eccentric resistance training. Pre- and post-training we assessed in-vivo maximum isometric torque at ankle angles corresponding to stretched and neutral muscle lengths, the passive torque-angle relationship, and isotonic power. The soleus and medial gastrocnemius were harvested for SSN measurements, with the untrained leg as a control. In old and young rats, muscles of the casted leg had smaller muscle wet weights (20-40%), physiological cross-sectional area (16-20%), and SSN (7-29%) than the control leg. Furthermore, maximum isometric torque (37-46%) and isotonic power (≈70%) decreased, and passive torque increased (+≈400%) from pre- to post-training for both age groups. Thus, irrespective of age, submaximal eccentric resistance training 3 days/week was ineffective for preventing the losses of muscle contractile tissue and mechanical function during casting.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837059","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}
Li Xue Wu,Jia Bao Su,Guang Ling Li,Meng Zhuang,Hai Jian Sun,Ji Ru Zhang
BACKGROUNDThe pathophysiology of delirium remains incompletely understood. The relationship between preoperative plasma concentrations of p-tau181, p-tau231, p-tau217, and T-tau proteins and postoperative delirium needs further validation. We aimed to verify whether these markers can identify and predict the occurrence and severity of postoperative delirium.METHODS172 older adults undergoing laparoscopic surgery were selected from a tertiary comprehensive hospital. All patients received intravenous anesthesia. Preoperative plasma concentrations of p-tau181, p-tau231, p-tau217, and T-tau proteins were measured using enzyme-linked immunosorbent assay. The occurrence and severity of postoperative delirium were respectively assessed using the 3D-CAM and DRS-R-98 scales.RESULTSOf 172 patients (mean age: 72±6 years, 34.9% female), 20 (12%) experienced postoperative delirium. Patients who developed postoperative delirium had higher preoperative plasma concentrations of p-tau181, p-tau231, p-tau217, and T-tau than those without. After adjusting for age, ASA, and education, preoperative concentrations of p-tau181 (OR 1.05, 95% CI: 1.03-1.08), p-tau217 (OR 1.02, 95% CI: 1.01-1.04), p-tau231 (OR 1.09, 95% CI: 1.04-1.14), and T-tau (OR 1.01, 95% CI: 1.00-1.02) were independently associated with postoperative delirium(P＜0.001). Preoperative plasma p-tau231 showed the highest diagnostic performance with an AUC of 0.966, surpassing p-tau181 (0.869), p-tau217 (0.775), and T-tau (0.750). P-tau231 also demonstrated the highest sensitivity (0.900) and specificity (0.967) for predicting postoperative delirium, compared to p-tau181, p-tau217, and T-tau.CONCLUSIONPreoperative plasma concentrations of p-tau181, p-tau231, and p-tau217 can effectively predict the occurrence and severity of postoperative delirium in older adult undergoing laparoscopic surgery, with p-tau231 demonstrating higher predictive value.
{"title":"Preoperative Plasma p-tau231，p-tau181 and p-tau217 are associated with Postoperative Delirium: a prospective study.","authors":"Li Xue Wu,Jia Bao Su,Guang Ling Li,Meng Zhuang,Hai Jian Sun,Ji Ru Zhang","doi":"10.1093/gerona/glaf058","DOIUrl":"https://doi.org/10.1093/gerona/glaf058","url":null,"abstract":"BACKGROUNDThe pathophysiology of delirium remains incompletely understood. The relationship between preoperative plasma concentrations of p-tau181, p-tau231, p-tau217, and T-tau proteins and postoperative delirium needs further validation. We aimed to verify whether these markers can identify and predict the occurrence and severity of postoperative delirium.METHODS172 older adults undergoing laparoscopic surgery were selected from a tertiary comprehensive hospital. All patients received intravenous anesthesia. Preoperative plasma concentrations of p-tau181, p-tau231, p-tau217, and T-tau proteins were measured using enzyme-linked immunosorbent assay. The occurrence and severity of postoperative delirium were respectively assessed using the 3D-CAM and DRS-R-98 scales.RESULTSOf 172 patients (mean age: 72±6 years, 34.9% female), 20 (12%) experienced postoperative delirium. Patients who developed postoperative delirium had higher preoperative plasma concentrations of p-tau181, p-tau231, p-tau217, and T-tau than those without. After adjusting for age, ASA, and education, preoperative concentrations of p-tau181 (OR 1.05, 95% CI: 1.03-1.08), p-tau217 (OR 1.02, 95% CI: 1.01-1.04), p-tau231 (OR 1.09, 95% CI: 1.04-1.14), and T-tau (OR 1.01, 95% CI: 1.00-1.02) were independently associated with postoperative delirium(P＜0.001). Preoperative plasma p-tau231 showed the highest diagnostic performance with an AUC of 0.966, surpassing p-tau181 (0.869), p-tau217 (0.775), and T-tau (0.750). P-tau231 also demonstrated the highest sensitivity (0.900) and specificity (0.967) for predicting postoperative delirium, compared to p-tau181, p-tau217, and T-tau.CONCLUSIONPreoperative plasma concentrations of p-tau181, p-tau231, and p-tau217 can effectively predict the occurrence and severity of postoperative delirium in older adult undergoing laparoscopic surgery, with p-tau231 demonstrating higher predictive value.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836529","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}
Andrew P Shoubridge, Lucy Carpenter, Erin Flynn, Lito E Papanicolas, Josephine Collins, David Gordon, David J Lynn, Craig Whitehead, Lex E X Leong, Monica Cations, David P De Souza, Vinod K Narayana, Jocelyn M Choo, Steve L Wesselingh, Maria Crotty, Maria C Inacio, Kerry Ivey, Steven L Taylor, Geraint B Rogers
Ageing-associated cognitive decline affects more than half of those in long-term residential aged care. Emerging evidence suggests that gut microbiome-host interactions influence the effects of modifiable risk factors. We investigated the relationship between gut microbiome characteristics and severity of cognitive impairment CI in 159 residents of long-term aged care. Severe CI was associated with a significantly increased abundance of proinflammatory bacterial species, including Methanobrevibacter smithii and Alistipes finegoldii, and decreased relative abundance of beneficial bacterial clades. Severe CI was associated with increased microbial capacity for methanogenesis, and reduced capacity for synthesis of short-chain fatty acids, neurotransmitters glutamate and gamma-aminobutyric acid, and amino acids required for neuro-protective lysosomal activity. These relationships were independent of age, sex, antibiotic exposure, and diet. Our findings implicate multiple gut microbiome-brain pathways in ageing-associated cognitive decline, including inflammation, neurotransmission, and autophagy, and highlight the potential to predict and prevent cognitive decline through microbiome-targeted strategies.
{"title":"Severe cognitive decline in long-term care is related to gut microbiome production of metabolites involved in neurotransmission, immunomodulation, and autophagy","authors":"Andrew P Shoubridge, Lucy Carpenter, Erin Flynn, Lito E Papanicolas, Josephine Collins, David Gordon, David J Lynn, Craig Whitehead, Lex E X Leong, Monica Cations, David P De Souza, Vinod K Narayana, Jocelyn M Choo, Steve L Wesselingh, Maria Crotty, Maria C Inacio, Kerry Ivey, Steven L Taylor, Geraint B Rogers","doi":"10.1093/gerona/glaf053","DOIUrl":"https://doi.org/10.1093/gerona/glaf053","url":null,"abstract":"Ageing-associated cognitive decline affects more than half of those in long-term residential aged care. Emerging evidence suggests that gut microbiome-host interactions influence the effects of modifiable risk factors. We investigated the relationship between gut microbiome characteristics and severity of cognitive impairment CI in 159 residents of long-term aged care. Severe CI was associated with a significantly increased abundance of proinflammatory bacterial species, including Methanobrevibacter smithii and Alistipes finegoldii, and decreased relative abundance of beneficial bacterial clades. Severe CI was associated with increased microbial capacity for methanogenesis, and reduced capacity for synthesis of short-chain fatty acids, neurotransmitters glutamate and gamma-aminobutyric acid, and amino acids required for neuro-protective lysosomal activity. These relationships were independent of age, sex, antibiotic exposure, and diet. Our findings implicate multiple gut microbiome-brain pathways in ageing-associated cognitive decline, including inflammation, neurotransmission, and autophagy, and highlight the potential to predict and prevent cognitive decline through microbiome-targeted strategies.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745078","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}
Scientific progress depends on the generosity of reviewers who assist editors by sharing their time and expertise in the peer review process. Lewis Lipsitz, Editor-in-Chief of The Medical Sciences Section of the Journal of Gerontology Series A, on behalf of the editorial leadership team, wishes to thank the following individuals for their assistance in reviewing manuscripts during 2024.
{"title":"Reviewer Acknowledgement - 2024","authors":"","doi":"10.1093/gerona/glaf012","DOIUrl":"https://doi.org/10.1093/gerona/glaf012","url":null,"abstract":"Scientific progress depends on the generosity of reviewers who assist editors by sharing their time and expertise in the peer review process. Lewis Lipsitz, Editor-in-Chief of The Medical Sciences Section of the Journal of Gerontology Series A, on behalf of the editorial leadership team, wishes to thank the following individuals for their assistance in reviewing manuscripts during 2024.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745011","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}
Marianne Chanti-Ketterl, María P Aranda, Brenda L Plassman
Background Organochlorine pesticides persist in the environment and body for extended periods. However, little is known about their long-term impact on cognition in older adults and if their influence differs by race/ethnicity (hereinafter ethnicity) and sex. Methods We evaluated cognitive function and organochlorine levels by ethnicity and sex in 979 adults, age 60+ from the National Health and Nutrition Examination Surveys (2011-2014). We utilized weighted linear generalized estimating equations to measure differences between seven log-transformed lipid-adjusted organochlorines (ng/g) and cognitive function. A composite cognitive function score was created using the mean of the z-scores from immediate and delayed of a word-list memory test, verbal fluency, and digit substitution test. Covariates included age, education, marital status, sex, and ethnicity. Exploratory sensitivity analyses included BMI, Ratio of Income-to-Poverty (IPR), and occupation, which were added to the models individually. Weighted sample included: 55.4% females; 79.8% NH-White; 9.2% NH-Black; 3.4% Mexican-American; 4.0% Other-Hispanic; 3.5% NH-Asian. Results We found significant differences in cognitive outcomes and organochlorine levels across ethnic and sex groups. The variability in cognitive performance and organochlorine exposure both within and between these groups, suggests that organochlorines may play a role in cognitive disparities, despite limited significant interaction effects. Sensitivity analyses adjusting for BMI, IPR, and longest occupation held indicated that most specific-organochlorine associations remained significant. Conclusion Our findings emphasize the importance of examining both the distributions of organochlorines and cognition by ethnicity and sex and their interactions to understand how each may contribute to cognitive health disparities in older adults.
{"title":"Ethnic and Sex Differences in the Association Between Organochlorine Exposure and Cognitive Function in Late Life","authors":"Marianne Chanti-Ketterl, María P Aranda, Brenda L Plassman","doi":"10.1093/gerona/glaf037","DOIUrl":"https://doi.org/10.1093/gerona/glaf037","url":null,"abstract":"Background Organochlorine pesticides persist in the environment and body for extended periods. However, little is known about their long-term impact on cognition in older adults and if their influence differs by race/ethnicity (hereinafter ethnicity) and sex. Methods We evaluated cognitive function and organochlorine levels by ethnicity and sex in 979 adults, age 60+ from the National Health and Nutrition Examination Surveys (2011-2014). We utilized weighted linear generalized estimating equations to measure differences between seven log-transformed lipid-adjusted organochlorines (ng/g) and cognitive function. A composite cognitive function score was created using the mean of the z-scores from immediate and delayed of a word-list memory test, verbal fluency, and digit substitution test. Covariates included age, education, marital status, sex, and ethnicity. Exploratory sensitivity analyses included BMI, Ratio of Income-to-Poverty (IPR), and occupation, which were added to the models individually. Weighted sample included: 55.4% females; 79.8% NH-White; 9.2% NH-Black; 3.4% Mexican-American; 4.0% Other-Hispanic; 3.5% NH-Asian. Results We found significant differences in cognitive outcomes and organochlorine levels across ethnic and sex groups. The variability in cognitive performance and organochlorine exposure both within and between these groups, suggests that organochlorines may play a role in cognitive disparities, despite limited significant interaction effects. Sensitivity analyses adjusting for BMI, IPR, and longest occupation held indicated that most specific-organochlorine associations remained significant. Conclusion Our findings emphasize the importance of examining both the distributions of organochlorines and cognition by ethnicity and sex and their interactions to understand how each may contribute to cognitive health disparities in older adults.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661375","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}
Giorgio DI GESSA, Mikaela Bloomberg, Rina So, Shaun Scholes, Thomas Byrne, Jinkook Lee, Sara D Adar, Paola Zaninotto
Background Although air pollution is associated with worse cognitive performance, whether these relationships differ by cognitive domain and which sources of air pollution are particularly detrimental to cognition remains understudied. This study examined associations between cognitive scores across three domains in older adults and 8-10 years of exposure to air pollutants (NO2, total PM2.5, and PM2.5 from different emission sources). Methods We used data from the 2018 Harmonized Cognitive Assessment Protocol sub-study of the English Longitudinal Study of Ageing (N=1,127). Outdoor concentrations of each pollutant were estimated for 2008/10-2017 and summarised using means and group-based trajectories. Linear regression models were used to assess long-term air pollution exposure relationships with memory, executive function, language, and global cognitive function after adjustment for key individual and neighbourhood-level confounders. Results Associations between air pollution trajectories and cognition are mostly inverted j-shaped, with respondents exposed to the highest residential levels of NO2 and total PM2.5 having worse performance for global cognition [β=-0.241; 95%CI=(-0.46,-0.02) and β=-0.334; 95%CI=(-0.55,-0.12) respectively] than those exposed to average levels of pollution. Similar associations were also found for executive function and memory (PM2.5 only), whereas more compelling dose-response evidence was found for language. Higher emissions from industry and residential combustion, as well as biofuel, coal, oil and natural gas combustion, were associated with worse language scores. Conclusions Air pollution and its sources have domain-specific associations with cognitive performance, with most consistent evidence observed for language. Continued efforts to reduce air pollution, particularly where levels are the highest, might benefit cognitive performance.
{"title":"Cognitive Performance and Long-term Exposure to Outdoor Air Pollution: Findings from the Harmonised Cognitive Assessment Protocol Sub-Study of the English Longitudinal Study of Ageing (ELSA-HCAP)","authors":"Giorgio DI GESSA, Mikaela Bloomberg, Rina So, Shaun Scholes, Thomas Byrne, Jinkook Lee, Sara D Adar, Paola Zaninotto","doi":"10.1093/gerona/glaf060","DOIUrl":"https://doi.org/10.1093/gerona/glaf060","url":null,"abstract":"Background Although air pollution is associated with worse cognitive performance, whether these relationships differ by cognitive domain and which sources of air pollution are particularly detrimental to cognition remains understudied. This study examined associations between cognitive scores across three domains in older adults and 8-10 years of exposure to air pollutants (NO2, total PM2.5, and PM2.5 from different emission sources). Methods We used data from the 2018 Harmonized Cognitive Assessment Protocol sub-study of the English Longitudinal Study of Ageing (N=1,127). Outdoor concentrations of each pollutant were estimated for 2008/10-2017 and summarised using means and group-based trajectories. Linear regression models were used to assess long-term air pollution exposure relationships with memory, executive function, language, and global cognitive function after adjustment for key individual and neighbourhood-level confounders. Results Associations between air pollution trajectories and cognition are mostly inverted j-shaped, with respondents exposed to the highest residential levels of NO2 and total PM2.5 having worse performance for global cognition [β=-0.241; 95%CI=(-0.46,-0.02) and β=-0.334; 95%CI=(-0.55,-0.12) respectively] than those exposed to average levels of pollution. Similar associations were also found for executive function and memory (PM2.5 only), whereas more compelling dose-response evidence was found for language. Higher emissions from industry and residential combustion, as well as biofuel, coal, oil and natural gas combustion, were associated with worse language scores. Conclusions Air pollution and its sources have domain-specific associations with cognitive performance, with most consistent evidence observed for language. Continued efforts to reduce air pollution, particularly where levels are the highest, might benefit cognitive performance.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"183 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641052","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}
Eileen M Crimmins, Belinda Hernandez, Claire Potter, Jung Ki Kim, Albert Higgins-Chen, Rose Anne Kenny, Aisling M O’Halloran, Bernadette McGuinness, Laura J Smyth, Claire Hill, Giovanni Fiorito, Jessica Faul, Amy Jayne McKnight, Cathal McCrory
Background Measures of epigenetic age have been linked to life circumstances and health outcomes in older populations. The similarity of these relationships across multiple populations in well-harmonized data has not been addressed. We examine links between epigenetic age, based on currently widely used indicators and key health outcomes in the Republic of Ireland, the United States, and Northern Ireland with harmonized, nationally representative data on their populations age 50 and older. Methods Data from 6,336 participants from the Irish Longitudinal Study on Ageing (TILDA), the Health and Retirement Study of the United States (HRS) and the Northern Ireland COhort for the Longitudinal study of Ageing (NICOLA) are used to investigate the association of accelerated epigenetic age based on three clocks (PhenoAge, GrimAge and DunedinPACE) with four health outcomes (mobility, grip strength, cognitive functioning, and mortality). Importantly, survey questions, population characteristics, and analysis pipelines are harmonized, and similar metrics are used for each health outcome. Results The three countries are remarkably similar in interrelationships among the clocks and in how the clocks relate to health outcomes across the three countries. These second- and third-generation clocks are significantly related to mortality, cognitive loss, strength, and mobility in the three countries. Conclusions For these three countries, epigenetic clocks appear to be highly comparable in their associations with aging health outcomes that reflect physical and cognitive functioning and mortality suggesting they capture a fundamental aging process.
{"title":"Epigenetic Clocks Relate to Four Age-Related Health Outcomes Similarly across Three Countries","authors":"Eileen M Crimmins, Belinda Hernandez, Claire Potter, Jung Ki Kim, Albert Higgins-Chen, Rose Anne Kenny, Aisling M O’Halloran, Bernadette McGuinness, Laura J Smyth, Claire Hill, Giovanni Fiorito, Jessica Faul, Amy Jayne McKnight, Cathal McCrory","doi":"10.1093/gerona/glaf036","DOIUrl":"https://doi.org/10.1093/gerona/glaf036","url":null,"abstract":"Background Measures of epigenetic age have been linked to life circumstances and health outcomes in older populations. The similarity of these relationships across multiple populations in well-harmonized data has not been addressed. We examine links between epigenetic age, based on currently widely used indicators and key health outcomes in the Republic of Ireland, the United States, and Northern Ireland with harmonized, nationally representative data on their populations age 50 and older. Methods Data from 6,336 participants from the Irish Longitudinal Study on Ageing (TILDA), the Health and Retirement Study of the United States (HRS) and the Northern Ireland COhort for the Longitudinal study of Ageing (NICOLA) are used to investigate the association of accelerated epigenetic age based on three clocks (PhenoAge, GrimAge and DunedinPACE) with four health outcomes (mobility, grip strength, cognitive functioning, and mortality). Importantly, survey questions, population characteristics, and analysis pipelines are harmonized, and similar metrics are used for each health outcome. Results The three countries are remarkably similar in interrelationships among the clocks and in how the clocks relate to health outcomes across the three countries. These second- and third-generation clocks are significantly related to mortality, cognitive loss, strength, and mobility in the three countries. Conclusions For these three countries, epigenetic clocks appear to be highly comparable in their associations with aging health outcomes that reflect physical and cognitive functioning and mortality suggesting they capture a fundamental aging process.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641054","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}
Karen Bandeen-Roche, Jiafeng Zhu, Qian-Li Xue, Brian Buta, Thomas Laskow, Jeremy D Walston, Ravi Varadhan
Resilience to stressors has emerged as a major gerontological concept aiming to promote more positive outcomes for older adults. Achieving this aim relies on determining mechanisms underlying capacity to respond resiliently. This paper seeks proof of principle for the hypothesis that physical aspects of said capacity are rooted in the fitness of one’s physiology governing stress response, conceptualized as a dynamical system. The Study of Physical Resilience in Aging (“SPRING”) leveraged stimulus-response experiments to characterize physiological fitness in older adults scheduled for one of three major stressors: Total knee replacement, incident hemodialysis, or bone marrow transplant in hematological cancer. Here we analyze Holter monitor time series characterizing heart rate variability (HRV), cortisol responses to adrenocorticotropic hormone (ACTH) stimulation, and repeated diurnal salivary cortisol assessment in the SPRING pilot (n=79). Principal component analysis was applied anticipating steady-state and “adaptation” mechanisms underlying the repeated physiological measures. Analytic features evidenced these mechanisms, supporting construct validity. Component scores were analyzed by major stressor, hypothesized surrogate physiologic measures (physical frailty phenotype, self-report of health), and demographic, health and behavioral characteristics. Scores differed substantially by stressor type and the surrogate physiologic measures, evidencing criterion validity. Our data support that HRV, ACTH and salivary cortisol stimulus-response data jointly assess adaptation capacity across three major stressors. We believe that SPRING is the first study in humans to concurrently query multiple physiologic systems using stimulus-response tests. Our findings lay groundwork for future validation with further data and to better forecast resilience of older adults to clinical stressors.
{"title":"Characterization of Dynamic Adaptation to Stressors using Multi-System Stimulus-Response Data: The Study of Physical Resilience in Aging Pilot","authors":"Karen Bandeen-Roche, Jiafeng Zhu, Qian-Li Xue, Brian Buta, Thomas Laskow, Jeremy D Walston, Ravi Varadhan","doi":"10.1093/gerona/glaf056","DOIUrl":"https://doi.org/10.1093/gerona/glaf056","url":null,"abstract":"Resilience to stressors has emerged as a major gerontological concept aiming to promote more positive outcomes for older adults. Achieving this aim relies on determining mechanisms underlying capacity to respond resiliently. This paper seeks proof of principle for the hypothesis that physical aspects of said capacity are rooted in the fitness of one’s physiology governing stress response, conceptualized as a dynamical system. The Study of Physical Resilience in Aging (“SPRING”) leveraged stimulus-response experiments to characterize physiological fitness in older adults scheduled for one of three major stressors: Total knee replacement, incident hemodialysis, or bone marrow transplant in hematological cancer. Here we analyze Holter monitor time series characterizing heart rate variability (HRV), cortisol responses to adrenocorticotropic hormone (ACTH) stimulation, and repeated diurnal salivary cortisol assessment in the SPRING pilot (n=79). Principal component analysis was applied anticipating steady-state and “adaptation” mechanisms underlying the repeated physiological measures. Analytic features evidenced these mechanisms, supporting construct validity. Component scores were analyzed by major stressor, hypothesized surrogate physiologic measures (physical frailty phenotype, self-report of health), and demographic, health and behavioral characteristics. Scores differed substantially by stressor type and the surrogate physiologic measures, evidencing criterion validity. Our data support that HRV, ACTH and salivary cortisol stimulus-response data jointly assess adaptation capacity across three major stressors. We believe that SPRING is the first study in humans to concurrently query multiple physiologic systems using stimulus-response tests. Our findings lay groundwork for future validation with further data and to better forecast resilience of older adults to clinical stressors.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631476","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}
Michelle M Mielke, Nicole R Fowler, Heather E Whitson, Heidi D Klepin, Antoine R Trammell, Ambar Kulshreshtha, Kyra S O’Brien, Margaret Manchester, Marcel E Salive, Jeff Williamson
The Alzheimer’s Disease in Older Adults with Chronic Conditions (ADACC) Network is funded by the National Institute on Aging as a U24 cooperative agreement. ADACC is an inclusive, multidisciplinary group across multiple institutions that is charged with the task of developing evidence-based strategies for the use and implementation of Alzheimer’s disease and related dementias (AD/ADRD) biomarkers among older adults with cognitive impairment and multiple chronic conditions (MCCs). This report summarizes highlights of the First Annual Symposium of ADACC, which was held in Winston-Salem, North Carolina, in April 2024. An overview of the ADACC network and goals were initially described, followed by a state of the science integrating biomarkers, AD/ADRD, and multiple chronic conditions. Multiple presentations on a variety of topics were featured, including the significance of MCCs in AD/ADRD, the effects of MCCs on Alzheimer’s blood-based biomarkers, the incorporation of AD/ADRD biomarkers into cancer care, the need to address racial and biomarker disparities, clinician and patient perspectives on plasma AD/ADRD biomarker testing, and ethical considerations. ADACC emphasized the importance of supporting emerging researchers and fostering a collaborative environment.
{"title":"Proceedings of the Alzheimer’s Diagnosis in Older Adults with Chronic Conditions (ADACC) Network Inaugural Annual Conference","authors":"Michelle M Mielke, Nicole R Fowler, Heather E Whitson, Heidi D Klepin, Antoine R Trammell, Ambar Kulshreshtha, Kyra S O’Brien, Margaret Manchester, Marcel E Salive, Jeff Williamson","doi":"10.1093/gerona/glaf052","DOIUrl":"https://doi.org/10.1093/gerona/glaf052","url":null,"abstract":"The Alzheimer’s Disease in Older Adults with Chronic Conditions (ADACC) Network is funded by the National Institute on Aging as a U24 cooperative agreement. ADACC is an inclusive, multidisciplinary group across multiple institutions that is charged with the task of developing evidence-based strategies for the use and implementation of Alzheimer’s disease and related dementias (AD/ADRD) biomarkers among older adults with cognitive impairment and multiple chronic conditions (MCCs). This report summarizes highlights of the First Annual Symposium of ADACC, which was held in Winston-Salem, North Carolina, in April 2024. An overview of the ADACC network and goals were initially described, followed by a state of the science integrating biomarkers, AD/ADRD, and multiple chronic conditions. Multiple presentations on a variety of topics were featured, including the significance of MCCs in AD/ADRD, the effects of MCCs on Alzheimer’s blood-based biomarkers, the incorporation of AD/ADRD biomarkers into cancer care, the need to address racial and biomarker disparities, clinician and patient perspectives on plasma AD/ADRD biomarker testing, and ethical considerations. ADACC emphasized the importance of supporting emerging researchers and fostering a collaborative environment.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576304","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}
Grazielle Caroline da Silva, Maisa Nascimento Soares Amaral, Diogo Barros Peruchetti, Virginia Soares Lemos
Aging is a major risk factor for cardiovascular disease, with hypertension being the most common outcome. Hypertension often stems from resistance arteries endothelial dysfunction. Recent research highlights the pivotal role of perivascular adipose tissue (PVAT) in regulating endothelial function. We hypothesized that PVAT senescence contributes to vascular dysfunction and hypertension during aging. We showed that naturally aged mice developed hypertension and elevated pro-inflammatory cytokines levels. Moreover, resistance mesenteric arteries showed impaired vascular relaxation that was normalized by apocynin, an antioxidant. The vascular dysfunction was endothelium- and PVAT-dependent, and marked by: decreased NO- and COX-dependent vascular relaxation, decreased expression of endothelial nitric oxide synthase (eNOS), and increased cyclooxygenase 2 (COX-2) and NADPH oxidase subunits p22phox and gp91phox expressions in the endothelium and PVAT. Additionally, we observed that PVAT shows greater signs of senescence, particularly with higher p16 expression, indicating that PVAT is more prone to age-related cellular aging. Our findings suggest that in resistance mesenteric arteries PVAT-derived factors are crucial for triggering and amplifying vascular dysfunction in aging, leading to hypertension. The underlying mechanisms involve downregulation of eNOS-derived NO, NADPH-oxidase-dependent oxidative stress, and COX-2-derived vascular contractile factors. This research improves our understanding of the mechanisms behind age-related vascular dysfunction and associated hypertension and opens perspectives for targeted therapeutic strategies.
{"title":"Upregulation of COX-2 and NADPH oxidase and reduced eNOS in perivascular adipose tissue are associated with resistance artery dysfunction and hypertension in naturally aged mice","authors":"Grazielle Caroline da Silva, Maisa Nascimento Soares Amaral, Diogo Barros Peruchetti, Virginia Soares Lemos","doi":"10.1093/gerona/glaf050","DOIUrl":"https://doi.org/10.1093/gerona/glaf050","url":null,"abstract":"Aging is a major risk factor for cardiovascular disease, with hypertension being the most common outcome. Hypertension often stems from resistance arteries endothelial dysfunction. Recent research highlights the pivotal role of perivascular adipose tissue (PVAT) in regulating endothelial function. We hypothesized that PVAT senescence contributes to vascular dysfunction and hypertension during aging. We showed that naturally aged mice developed hypertension and elevated pro-inflammatory cytokines levels. Moreover, resistance mesenteric arteries showed impaired vascular relaxation that was normalized by apocynin, an antioxidant. The vascular dysfunction was endothelium- and PVAT-dependent, and marked by: decreased NO- and COX-dependent vascular relaxation, decreased expression of endothelial nitric oxide synthase (eNOS), and increased cyclooxygenase 2 (COX-2) and NADPH oxidase subunits p22phox and gp91phox expressions in the endothelium and PVAT. Additionally, we observed that PVAT shows greater signs of senescence, particularly with higher p16 expression, indicating that PVAT is more prone to age-related cellular aging. Our findings suggest that in resistance mesenteric arteries PVAT-derived factors are crucial for triggering and amplifying vascular dysfunction in aging, leading to hypertension. The underlying mechanisms involve downregulation of eNOS-derived NO, NADPH-oxidase-dependent oxidative stress, and COX-2-derived vascular contractile factors. This research improves our understanding of the mechanisms behind age-related vascular dysfunction and associated hypertension and opens perspectives for targeted therapeutic strategies.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546486","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}
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