Age-related changes in gut microbiota composition have been implicated in brain aging and cognitive decline, acting through the gut-brain axis on amyloid accumulation, tau pathology, synapse damage, and glial activation. Live microbial approaches such as probiotics, prebiotics, and fecal microbiota transplantation address this mechanism, but they still suffer from low efficacy and unknown safety issues. We tested whether abdominal ultrasound, an approach that does not involve microbes, can alleviate age-related neurodegeneration in the senescence-accelerated mouse strain SAMP8. We treated 6-month-old male SAMP8 mice for 1 month. We then assessed behavior, neuropathology, and synaptic proteins, and quantified four pre-specified fecal bacterial taxa. Ultrasound preserved neuronal survival in the hippocampal CA3, decreased amyloid-β load in the cortex and CA3, decreased tau hyperphosphorylation in all three regions, reduced Iba-1 and GFAP immunoreactive areas, and increased synaptophysin and cortical PSD-95. Neuronal survival in the cortex and CA1 did not differ significantly from sham-treated SAMP8 mice. In the gut microbiota, ultrasound significantly reduced the enriched taxon Tyzzerella, whereas the changes in Lactobacillus, Akkermansia and Atopobiaceae were large in magnitude but not statistically significant. In an exploratory analysis, four of 64 microbiota–neuropathology associations survived correction for multiple testing. Neither object recognition memory nor spatial memory differed significantly between treated and sham-treated SAMP8 mice. Abdominal ultrasound applied to the periphery therefore reduced age-associated neuropathology in the brain, accompanied by changes in specific gut microbial taxa whose causal contribution remains untested.
{"title":"Abdominal ultrasound mitigates neurodegenerative pathology and alters specific gut microbial taxa in senescence-accelerated mice","authors":"Hanlin Jiang, Tingrui Zhao, Xiaochen Zhang, Hideki Moriyama","doi":"10.1093/gerona/glag250","DOIUrl":"https://doi.org/10.1093/gerona/glag250","url":null,"abstract":"Age-related changes in gut microbiota composition have been implicated in brain aging and cognitive decline, acting through the gut-brain axis on amyloid accumulation, tau pathology, synapse damage, and glial activation. Live microbial approaches such as probiotics, prebiotics, and fecal microbiota transplantation address this mechanism, but they still suffer from low efficacy and unknown safety issues. We tested whether abdominal ultrasound, an approach that does not involve microbes, can alleviate age-related neurodegeneration in the senescence-accelerated mouse strain SAMP8. We treated 6-month-old male SAMP8 mice for 1 month. We then assessed behavior, neuropathology, and synaptic proteins, and quantified four pre-specified fecal bacterial taxa. Ultrasound preserved neuronal survival in the hippocampal CA3, decreased amyloid-β load in the cortex and CA3, decreased tau hyperphosphorylation in all three regions, reduced Iba-1 and GFAP immunoreactive areas, and increased synaptophysin and cortical PSD-95. Neuronal survival in the cortex and CA1 did not differ significantly from sham-treated SAMP8 mice. In the gut microbiota, ultrasound significantly reduced the enriched taxon Tyzzerella, whereas the changes in Lactobacillus, Akkermansia and Atopobiaceae were large in magnitude but not statistically significant. In an exploratory analysis, four of 64 microbiota–neuropathology associations survived correction for multiple testing. Neither object recognition memory nor spatial memory differed significantly between treated and sham-treated SAMP8 mice. Abdominal ultrasound applied to the periphery therefore reduced age-associated neuropathology in the brain, accompanied by changes in specific gut microbial taxa whose causal contribution remains untested.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"285 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221337","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}
Abstract Background Prevailing scientific evidence suggests that extreme heat poses a substantial threat to the health and well-being of older adults in the Sunbelt cities of the United States. However, prior research has not adequately addressed the specific socio-demographic, health-related vulnerabilities, and coping-strategic factors influencing heat stress among older urban populations. Methods Informed by the Socio-Ecological Model, this study adopts a retrospective cohort study design to investigate the predictors and experiences of heat stress among older adults. Data from older adults in Los Angeles, Houston, and Phoenix were analyzed using thematic and multiple binary logistic regression analyses. Results The results reveal that much older adults (aged 80 +) were less likely to experience heat stress compared to their relatively younger counterparts. Also, marital status, income, respiratory diseases, physical activity, taking cool showers, and city of residence were significantly associated with a higher risk of suffering heat stress. The qualitative results uncovered individual-level behavioural adjustment as an effective coping mechanism during extreme heat events. Conclusion These results underscore the complex interplay of behavioral, socio-demographic, and health-related factors influencing heat stress among older adults. The study recommends that urban health strategies prioritize these demographics, enhancing support systems and coping mechanisms to reduce vulnerability to heat stress among older urban populations.
{"title":"Heat stress and coping strategies among older adults in three Sunbelt cities in the United States","authors":"Cornelius Dassah,Peter Crank,Leah Jones-Crank","doi":"10.1093/gerona/glag239","DOIUrl":"https://doi.org/10.1093/gerona/glag239","url":null,"abstract":"Abstract Background Prevailing scientific evidence suggests that extreme heat poses a substantial threat to the health and well-being of older adults in the Sunbelt cities of the United States. However, prior research has not adequately addressed the specific socio-demographic, health-related vulnerabilities, and coping-strategic factors influencing heat stress among older urban populations. Methods Informed by the Socio-Ecological Model, this study adopts a retrospective cohort study design to investigate the predictors and experiences of heat stress among older adults. Data from older adults in Los Angeles, Houston, and Phoenix were analyzed using thematic and multiple binary logistic regression analyses. Results The results reveal that much older adults (aged 80 +) were less likely to experience heat stress compared to their relatively younger counterparts. Also, marital status, income, respiratory diseases, physical activity, taking cool showers, and city of residence were significantly associated with a higher risk of suffering heat stress. The qualitative results uncovered individual-level behavioural adjustment as an effective coping mechanism during extreme heat events. Conclusion These results underscore the complex interplay of behavioral, socio-demographic, and health-related factors influencing heat stress among older adults. The study recommends that urban health strategies prioritize these demographics, enhancing support systems and coping mechanisms to reduce vulnerability to heat stress among older urban populations.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088802","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 W McDade,Sofia Carrera,Calen P Ryan,Elijah Watson,Linda S Adair,Nanette R Lee,Delia B Carba,Julie L MacIsaac,Kristy Dever,Michael S Kobor,Christopher W Kuzawa
Abstract Age-related increases in chronic systemic inflammation are strong predictors of morbidity and mortality in high income countries, but evidence is lacking from lower- and middle-income settings where infectious diseases are more prevalent and rates of overweight and obesity are relatively low. Here we evaluate two complementary measures of chronic inflammation—plasma C-reactive protein (CRP) and a DNA methylation–based surrogate (DNAm-CRP)—measured at baseline as predictors of physical capacity, cognitive function, and cardiometabolic disease seven years later among women in the Philippines (N = 953; 43-75 years at follow-up). Levels of CRP and DNAm-CRP were not strongly associated with age. Both measures predicted subsequent declines in physical and functional capacity, increased incidence of diabetes and hypertension, and poorer cognitive performance, after adjustment for baseline status and other covariates. DNAm-CRP performed comparably to CRP, and was robust to variation in white blood cell composition and acute infectious symptoms at the time of sampling. These findings demonstrate that chronic inflammation is associated with multiple dimensions of aging in a lower-middle income setting, and highlights the utility of inflammatory biomarkers as scalable tools for global aging research.
{"title":"Chronic inflammation and multiple dimensions of aging among women in the Philippines","authors":"Thomas W McDade,Sofia Carrera,Calen P Ryan,Elijah Watson,Linda S Adair,Nanette R Lee,Delia B Carba,Julie L MacIsaac,Kristy Dever,Michael S Kobor,Christopher W Kuzawa","doi":"10.1093/gerona/glag246","DOIUrl":"https://doi.org/10.1093/gerona/glag246","url":null,"abstract":"Abstract Age-related increases in chronic systemic inflammation are strong predictors of morbidity and mortality in high income countries, but evidence is lacking from lower- and middle-income settings where infectious diseases are more prevalent and rates of overweight and obesity are relatively low. Here we evaluate two complementary measures of chronic inflammation—plasma C-reactive protein (CRP) and a DNA methylation–based surrogate (DNAm-CRP)—measured at baseline as predictors of physical capacity, cognitive function, and cardiometabolic disease seven years later among women in the Philippines (N = 953; 43-75 years at follow-up). Levels of CRP and DNAm-CRP were not strongly associated with age. Both measures predicted subsequent declines in physical and functional capacity, increased incidence of diabetes and hypertension, and poorer cognitive performance, after adjustment for baseline status and other covariates. DNAm-CRP performed comparably to CRP, and was robust to variation in white blood cell composition and acute infectious symptoms at the time of sampling. These findings demonstrate that chronic inflammation is associated with multiple dimensions of aging in a lower-middle income setting, and highlights the utility of inflammatory biomarkers as scalable tools for global aging research.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088803","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}
Paul Diez-Echave,Rosario Ortolá,David Martínez-Gómez,José Luis Peñalvo,Ligia J Domínguez,Fernando Rodríguez-Artalejo,Mercedes Sotos-Prieto
Abstract Background Frailty is a major determinant of disability and adverse outcomes in older adults. The Planetary Health Diet (PHD), a plant-based dietary pattern promoting environmental sustainability, has been associated with lower mortality and reduced chronic disease risk. We examined the association between adherence to the Planetary Health Diet Index (PHDI) and frailty over time using repeated frailty assessments. Methods Data came from two cohorts of community-dwelling older adults: Seniors-ENRICA-1 (2008-2015; ≥60 years; n = 3,289) and Seniors-ENRICA-2 (2015-2023; ≥65 years; n = 3,273). Baseline diet was assessed using a validated diet history, and adherence to the PHD was assessed using the PHDI (0-140), based on 15 food groups. Frailty was defined by the Fried phenotype (≥3 criteria of exhaustion, low physical activity, slow gait, muscle weakness, unintentional weight loss). Generalized estimating equation (GEE) models estimated odds ratios (OR) and 95% confidence intervals (CI) for frailty across PHDI tertiles, adjusting for sociodemographic, lifestyle, and clinical factors. Results Higher PHDI adherence was consistently associated with lower odds of frailty over time. Comparing highest vs. lowest tertiles, multivariable-adjusted ORs (95% CI) were 0.62 (0.42, 0.92) in Seniors-ENRICA-1, 0.40 (0.24, 0.65) in Seniors-ENRICA-2 and 0.52 (0.38, 0.70) in the pooled analyses. Higher PHDI adherence was primarily associated with lower odds of low physical activity, while vegetables and fruits showed the strongest independent associations among individual PHDI components. Conclusions Greater PHDI adherence is associated with lower odds of frailty in Spanish older adults, supporting the potential role of sustainable, plant-based dietary patterns for healthy ageing.
{"title":"Planetary Health Diet Adherence and Frailty in Older Adults: Evidence from the Seniors-ENRICA Cohorts","authors":"Paul Diez-Echave,Rosario Ortolá,David Martínez-Gómez,José Luis Peñalvo,Ligia J Domínguez,Fernando Rodríguez-Artalejo,Mercedes Sotos-Prieto","doi":"10.1093/gerona/glag244","DOIUrl":"https://doi.org/10.1093/gerona/glag244","url":null,"abstract":"Abstract Background Frailty is a major determinant of disability and adverse outcomes in older adults. The Planetary Health Diet (PHD), a plant-based dietary pattern promoting environmental sustainability, has been associated with lower mortality and reduced chronic disease risk. We examined the association between adherence to the Planetary Health Diet Index (PHDI) and frailty over time using repeated frailty assessments. Methods Data came from two cohorts of community-dwelling older adults: Seniors-ENRICA-1 (2008-2015; ≥60 years; n = 3,289) and Seniors-ENRICA-2 (2015-2023; ≥65 years; n = 3,273). Baseline diet was assessed using a validated diet history, and adherence to the PHD was assessed using the PHDI (0-140), based on 15 food groups. Frailty was defined by the Fried phenotype (≥3 criteria of exhaustion, low physical activity, slow gait, muscle weakness, unintentional weight loss). Generalized estimating equation (GEE) models estimated odds ratios (OR) and 95% confidence intervals (CI) for frailty across PHDI tertiles, adjusting for sociodemographic, lifestyle, and clinical factors. Results Higher PHDI adherence was consistently associated with lower odds of frailty over time. Comparing highest vs. lowest tertiles, multivariable-adjusted ORs (95% CI) were 0.62 (0.42, 0.92) in Seniors-ENRICA-1, 0.40 (0.24, 0.65) in Seniors-ENRICA-2 and 0.52 (0.38, 0.70) in the pooled analyses. Higher PHDI adherence was primarily associated with lower odds of low physical activity, while vegetables and fruits showed the strongest independent associations among individual PHDI components. Conclusions Greater PHDI adherence is associated with lower odds of frailty in Spanish older adults, supporting the potential role of sustainable, plant-based dietary patterns for healthy ageing.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088804","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}
Abstract Background Within gerontology, various theoretical perspectives on what it means to age successfully have emerged over recent decades (5) and garnered empirical support. Similarly, within medicine and related healthcare fields, research and practice have focused on healthy living in terms of physical health, mental health, and well-being. In recent years, the practice of Lifestyle Medicine (nutrition, physical activity, stress management, restorative sleep, social connection, and avoidance of risky substances) has emerged to describe the role of such lifestyle factors on health. Methods The present article proposes a pathway to integrate lifestyle medicine with successful aging. We take a holistic approach to develop a model that merges the foundational pillars of lifestyle medicine with the principles of successful aging. Conclusions This new approach to exploring the linkages between the principles of lifestyle medicine and the essential components of successful aging highlights how proactive behavioral health strategies related to nutrition, exercise, sleep, stress, and substances could play a role in fostering optimal aging in cognitive and physical functioning and disease prevention, thereby potentially yielding more positive outcomes for aging well.
{"title":"The Role of Lifestyle Medicine in Shaping and Supporting Successful Aging","authors":"Teri A Undem,Heather R Fuller","doi":"10.1093/gerona/glag243","DOIUrl":"https://doi.org/10.1093/gerona/glag243","url":null,"abstract":"Abstract Background Within gerontology, various theoretical perspectives on what it means to age successfully have emerged over recent decades (5) and garnered empirical support. Similarly, within medicine and related healthcare fields, research and practice have focused on healthy living in terms of physical health, mental health, and well-being. In recent years, the practice of Lifestyle Medicine (nutrition, physical activity, stress management, restorative sleep, social connection, and avoidance of risky substances) has emerged to describe the role of such lifestyle factors on health. Methods The present article proposes a pathway to integrate lifestyle medicine with successful aging. We take a holistic approach to develop a model that merges the foundational pillars of lifestyle medicine with the principles of successful aging. Conclusions This new approach to exploring the linkages between the principles of lifestyle medicine and the essential components of successful aging highlights how proactive behavioral health strategies related to nutrition, exercise, sleep, stress, and substances could play a role in fostering optimal aging in cognitive and physical functioning and disease prevention, thereby potentially yielding more positive outcomes for aging well.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088805","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}
Rong Du, Swarna Vishwanath, Zimu Wu, Aung Zaw Zaw Phyo, Suzanne G Orchard, Kerry Sheets, Michael E Ernst, Joanne Ryan
Background Multimorbidity is common in older adults, but sex differences in chronic condition clustering remain unclear. This study explored multimorbidity clusters and their associations with all-cause mortality among community-dwelling adults aged 70 years and over. Methods This was a secondary analysis of data from 16,095 Australian ASPREE participants aged ≥70 years without prior dementia or cardiovascular disease. Fifteen baseline chronic conditions were grouped using latent class analysis (LCA). Observed-to-expected (O/E) ratios characterized conditions over-represented within clusters, and Cox proportional hazards models assessed associations with all-cause mortality. Results Among 16,095 participants (mean age 75.3 years), 88.3% had multimorbidity at baseline; 4,217 deaths occurred over a median follow-up of 10.85 years. Five clusters were identified overall: hypertension & dyslipidemia (52.1%), gout & metabolic (14.4%), depressive symptoms, osteoporosis & frailty (10.0%), anemia & kidney disease (10.2%), and hypotension, thyroid disorder & past cancer (13.3%). Sex-stratified analyses revealed three clusters in males and four in females. The frailty, depressive symptoms & osteoporosis cluster was associated with higher mortality in both sexes (aHR 1.56 [95% CI 1.40–1.73] in males; 1.68 [1.49–1.89] in females). Higher mortality was also observed for the metabolic, gout & kidney disease cluster in males (aHR 1.63 [1.47–1.81]) and the gout, anemia & kidney disease cluster in females (aHR 1.96 [1.74–2.21]). Conclusions Distinct multimorbidity clusters were identified overall and in sex-stratified analyses. These hypothesis-generating findings suggest the potential clinical utility of multimorbidity clusters to identify individuals at increased risk of death, but further research is needed.
背景：多病在老年人中很常见，但慢性疾病聚类的性别差异尚不清楚。本研究探讨了70岁及以上社区居民的多发病群及其与全因死亡率的关系。方法：对16095名年龄≥70岁、既往无痴呆或心血管疾病的澳大利亚ASPREE参与者的资料进行二次分析。使用潜类分析（LCA）对15种基线慢性疾病进行分组。观察到的期望比率（O/E）表征了群集中过度代表的疾病，Cox比例风险模型评估了与全因死亡率的关联。结果在16095名参与者（平均年龄75.3岁）中，88.3%的人在基线时患有多重疾病；在10.85年的中位随访期间发生了4217例死亡。总体上确定了5类：高血压和血脂异常（52.1%）、痛风和代谢（14.4%）、抑郁症状、骨质疏松和虚弱（10.0%）、贫血和肾脏疾病（10.2%）、低血压、甲状腺疾病和既往癌症（13.3%）。性别分层分析显示男性中有3个集群，女性中有4个集群。虚弱、抑郁症状和骨质疏松群集与两性较高的死亡率相关（男性aHR为1.56 [95% CI 1.40-1.73]，女性为1.68[1.49-1.89]）。男性代谢、痛风和肾脏疾病组（aHR 1.63[1.47-1.81]）和女性痛风、贫血和肾脏疾病组（aHR 1.96[1.74-2.21]）的死亡率也较高。结论：在性别分层分析中发现了明显的多发病群。这些产生假设的发现表明，多病聚集性在识别死亡风险增加的个体方面具有潜在的临床应用价值，但还需要进一步的研究。
{"title":"Sex-specific multimorbidity clusters and all-cause mortality among community-dwelling older adults: findings from the ASPREE cohort","authors":"Rong Du, Swarna Vishwanath, Zimu Wu, Aung Zaw Zaw Phyo, Suzanne G Orchard, Kerry Sheets, Michael E Ernst, Joanne Ryan","doi":"10.1093/gerona/glag245","DOIUrl":"https://doi.org/10.1093/gerona/glag245","url":null,"abstract":"Background Multimorbidity is common in older adults, but sex differences in chronic condition clustering remain unclear. This study explored multimorbidity clusters and their associations with all-cause mortality among community-dwelling adults aged 70 years and over. Methods This was a secondary analysis of data from 16,095 Australian ASPREE participants aged ≥70 years without prior dementia or cardiovascular disease. Fifteen baseline chronic conditions were grouped using latent class analysis (LCA). Observed-to-expected (O/E) ratios characterized conditions over-represented within clusters, and Cox proportional hazards models assessed associations with all-cause mortality. Results Among 16,095 participants (mean age 75.3 years), 88.3% had multimorbidity at baseline; 4,217 deaths occurred over a median follow-up of 10.85 years. Five clusters were identified overall: hypertension & dyslipidemia (52.1%), gout & metabolic (14.4%), depressive symptoms, osteoporosis & frailty (10.0%), anemia & kidney disease (10.2%), and hypotension, thyroid disorder & past cancer (13.3%). Sex-stratified analyses revealed three clusters in males and four in females. The frailty, depressive symptoms & osteoporosis cluster was associated with higher mortality in both sexes (aHR 1.56 [95% CI 1.40–1.73] in males; 1.68 [1.49–1.89] in females). Higher mortality was also observed for the metabolic, gout & kidney disease cluster in males (aHR 1.63 [1.47–1.81]) and the gout, anemia & kidney disease cluster in females (aHR 1.96 [1.74–2.21]). Conclusions Distinct multimorbidity clusters were identified overall and in sex-stratified analyses. These hypothesis-generating findings suggest the potential clinical utility of multimorbidity clusters to identify individuals at increased risk of death, but further research is needed.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086408","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}
Kenneth Ladd Seldeen, Saurav Saha, Baolin Wang, Bhavana Sreevelu, Ramkumar Thiyagarajan, Ilsa Nadeem, Iqra Nadeem, Yonas Z Redae, Merced Marie Leiker, Bruce Robert Troen
Frailty and cognitive decline are common among older adults, increasing risks of disability and loss of independence. We have previously demonstrated in mice that short session (≤10 minute) high-intensity interval training (HIIT) is an effective intervention for frailty, but benefits for cognitive function and reducing hallmarks of aging have not been examined. Thus, we studied 24-month-old female C57BL/6J mice from our previous study that remained sedentary or performed a 10-minute HIIT regimen 3-days-a-week for 8 weeks. We found HIIT improved cognitive aspects including an increase in T-maze alternation % and novel object recognition, but no differences were observed in Barnes maze or light-dark preference. To explore HIIT impacts on the hallmarks of aging, we examined liver, gastrocnemius muscle, and cortex brain tissues for mitochondria expression, autophagy, cellular senescence, and telomere length. HIIT increased expression of mitochondrial complexes I and V, as well as PGC1α and SIRT3 in all tissues. Autophagy marker beclin was elevated across all tissues, while p62 was increased in liver and muscle but not in the cortex, and LC3-II was lower in muscle and liver. Senescence marker p16 was lower in HIIT muscle and liver, whereas p21 decreased in liver but increased in muscle. Telomere lengths were greater in liver, but no changes in muscle or cortex. Additionally, within the group of sedentary mice, we identified differences in hallmarks of aging that potentially underlie frailty as measured using different mouse frailty assessment tools. These results highlight the potential for multi-tissue geroprotective benefits of short session HIIT to reduce frailty and improve cognition for healthy aging.
{"title":"Hallmarks of Aging Associate with High Intensity Interval Training Benefits and Frailty in Female C57Bl/6J Mice","authors":"Kenneth Ladd Seldeen, Saurav Saha, Baolin Wang, Bhavana Sreevelu, Ramkumar Thiyagarajan, Ilsa Nadeem, Iqra Nadeem, Yonas Z Redae, Merced Marie Leiker, Bruce Robert Troen","doi":"10.1093/gerona/glag242","DOIUrl":"https://doi.org/10.1093/gerona/glag242","url":null,"abstract":"Frailty and cognitive decline are common among older adults, increasing risks of disability and loss of independence. We have previously demonstrated in mice that short session (≤10 minute) high-intensity interval training (HIIT) is an effective intervention for frailty, but benefits for cognitive function and reducing hallmarks of aging have not been examined. Thus, we studied 24-month-old female C57BL/6J mice from our previous study that remained sedentary or performed a 10-minute HIIT regimen 3-days-a-week for 8 weeks. We found HIIT improved cognitive aspects including an increase in T-maze alternation % and novel object recognition, but no differences were observed in Barnes maze or light-dark preference. To explore HIIT impacts on the hallmarks of aging, we examined liver, gastrocnemius muscle, and cortex brain tissues for mitochondria expression, autophagy, cellular senescence, and telomere length. HIIT increased expression of mitochondrial complexes I and V, as well as PGC1α and SIRT3 in all tissues. Autophagy marker beclin was elevated across all tissues, while p62 was increased in liver and muscle but not in the cortex, and LC3-II was lower in muscle and liver. Senescence marker p16 was lower in HIIT muscle and liver, whereas p21 decreased in liver but increased in muscle. Telomere lengths were greater in liver, but no changes in muscle or cortex. Additionally, within the group of sedentary mice, we identified differences in hallmarks of aging that potentially underlie frailty as measured using different mouse frailty assessment tools. These results highlight the potential for multi-tissue geroprotective benefits of short session HIIT to reduce frailty and improve cognition for healthy aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048826","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}
Daisy V Zavala, Sharon H Kim, John M Felt, Zita Oravecz, Martin J Sliwinski, Jennifer E Graham-Engeland, Christopher G Engeland, Kristin Bernard, Krishna R Veeramah, Stacey B Scott
Greater age deviation (AgeDev), in which a person’s biological age is older than their chronological age, is associated with worse cognitive performance. Most findings, however, rely on lab-administered cognitive measures and do not account for time-ordered effects of practice. The present study leveraged a measurement burst dataset to examine six distinct features of cognitive performance (peak performance, change in peak performance, intraindividual variability, forgetting, retest-related gains), and explored whether individual differences in these features can be predicted by AgeDev. In a sample of 139 adults aged 25-65, baseline AgeDev (Horvath1, Horvath2, Hannum, PhenoAge, GrimAge), DunedinPACE, and SystemsAge were derived from DNA methylation. Across four annual high-frequency assessment bursts, processing speed and working memory were assessed via a Symbol Search and N-Back task, respectively. Using Bayesian Double Exponential Models (BDEMs), we found that baseline peak performance was lower for individuals with greater AgeDev, DunedinPACE, and chronological age. Interestingly, individuals with greater AgeDev and faster DunedinPACE showed greater retest-related gains within and across bursts. Neither AgeDev nor chronological age predicted differences in cognitive change across time. Individuals with greater AgeDev showed more intraindividual variability in processing speed. Finally, greater chronological age (but not AgeDev) was linked with more forgetting between bursts in both tasks. These findings underscore the value of multidimensional indices of cognitive performance. Importantly, even in a sample spanning young adulthood through early old age, such indices may provide unique information regarding the nature of longitudinal patterns in cognition associated with chronological or biological aging.
{"title":"Exploring Epigenetic Aging and Cognitive Change in Middle Adulthood","authors":"Daisy V Zavala, Sharon H Kim, John M Felt, Zita Oravecz, Martin J Sliwinski, Jennifer E Graham-Engeland, Christopher G Engeland, Kristin Bernard, Krishna R Veeramah, Stacey B Scott","doi":"10.1093/gerona/glag240","DOIUrl":"https://doi.org/10.1093/gerona/glag240","url":null,"abstract":"Greater age deviation (AgeDev), in which a person’s biological age is older than their chronological age, is associated with worse cognitive performance. Most findings, however, rely on lab-administered cognitive measures and do not account for time-ordered effects of practice. The present study leveraged a measurement burst dataset to examine six distinct features of cognitive performance (peak performance, change in peak performance, intraindividual variability, forgetting, retest-related gains), and explored whether individual differences in these features can be predicted by AgeDev. In a sample of 139 adults aged 25-65, baseline AgeDev (Horvath1, Horvath2, Hannum, PhenoAge, GrimAge), DunedinPACE, and SystemsAge were derived from DNA methylation. Across four annual high-frequency assessment bursts, processing speed and working memory were assessed via a Symbol Search and N-Back task, respectively. Using Bayesian Double Exponential Models (BDEMs), we found that baseline peak performance was lower for individuals with greater AgeDev, DunedinPACE, and chronological age. Interestingly, individuals with greater AgeDev and faster DunedinPACE showed greater retest-related gains within and across bursts. Neither AgeDev nor chronological age predicted differences in cognitive change across time. Individuals with greater AgeDev showed more intraindividual variability in processing speed. Finally, greater chronological age (but not AgeDev) was linked with more forgetting between bursts in both tasks. These findings underscore the value of multidimensional indices of cognitive performance. Importantly, even in a sample spanning young adulthood through early old age, such indices may provide unique information regarding the nature of longitudinal patterns in cognition associated with chronological or biological aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"103 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048828","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}
Tengfei Liang, Lixia Wang, Shujuan Kang, Xiaoyan Pang, Hexin Yan
Although mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in aging and age-related neurodegenerative diseases, the impact of ALDH2 on age-related cognitive deficits and its underlying mechanisms have not been fully elucidated. This study aimed to explore the effects of ALDH2 on cognitive deficits in D-galactose-induced aging mice and illustrate the potential molecular mechanisms. We treated D-galactose-induced aging mice with Alda-1 (a potent agonist of ALDH2) for eight weeks and observed the alterations in behavior, levels of oxidative stress and neuroinflammation, mitochondrial function, and expression of mitochondrial biogenesis-related genes. The results revealed that Alda-1 alleviated neuropathological changes in the hippocampus and ameliorated cognitive deficits in D-galactose-induced aging mice. Administration of Alda-1 further reduced the levels of 4-HNE, MDA, 3-NT, IL-6, TNF-α, and IL-1β; enhanced Mn-SOD and CAT activities; increased GSH and ATP levels and mitochondrial content; and upregulated PGC-1α/NRF-1/TFAM expression in the hippocampus of D-galactose-induced aging mice. Moreover, in D-galactose-treated HT22 cells, we found that the SIRT1 inhibitor EX527 reversed the Alda-1-induced upregulation of PGC-1α, suggesting that the Alda-1-induced upregulation of PGC-1α is associated with SIRT1 signaling. Collectively, Alda-1 ameliorated cognitive deficits in D-galactose-induced aging mice by reducing neuroinflammation, enhancing antioxidative capability, promoting mitochondrial biogenesis, and modulating the SIRT1/PGC-1α signaling pathway.
{"title":"Alda-1 Alleviates the Cognitive Deficits in D-galactose-induced Aging Mice by Regulating Oxidative Stress, Neuroinflammation, and Mitochondrial Biogenesis","authors":"Tengfei Liang, Lixia Wang, Shujuan Kang, Xiaoyan Pang, Hexin Yan","doi":"10.1093/gerona/glag241","DOIUrl":"https://doi.org/10.1093/gerona/glag241","url":null,"abstract":"Although mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in aging and age-related neurodegenerative diseases, the impact of ALDH2 on age-related cognitive deficits and its underlying mechanisms have not been fully elucidated. This study aimed to explore the effects of ALDH2 on cognitive deficits in D-galactose-induced aging mice and illustrate the potential molecular mechanisms. We treated D-galactose-induced aging mice with Alda-1 (a potent agonist of ALDH2) for eight weeks and observed the alterations in behavior, levels of oxidative stress and neuroinflammation, mitochondrial function, and expression of mitochondrial biogenesis-related genes. The results revealed that Alda-1 alleviated neuropathological changes in the hippocampus and ameliorated cognitive deficits in D-galactose-induced aging mice. Administration of Alda-1 further reduced the levels of 4-HNE, MDA, 3-NT, IL-6, TNF-α, and IL-1β; enhanced Mn-SOD and CAT activities; increased GSH and ATP levels and mitochondrial content; and upregulated PGC-1α/NRF-1/TFAM expression in the hippocampus of D-galactose-induced aging mice. Moreover, in D-galactose-treated HT22 cells, we found that the SIRT1 inhibitor EX527 reversed the Alda-1-induced upregulation of PGC-1α, suggesting that the Alda-1-induced upregulation of PGC-1α is associated with SIRT1 signaling. Collectively, Alda-1 ameliorated cognitive deficits in D-galactose-induced aging mice by reducing neuroinflammation, enhancing antioxidative capability, promoting mitochondrial biogenesis, and modulating the SIRT1/PGC-1α signaling pathway.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"194 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048827","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}
Maryam Ghahremani, Dylan X Guan, Clive Ballard, Byron Creese, Anne Corbett, Ellie Pickering, Eric E Smith, Zahinoor Ismail
Background Cognitive reserve (CR) is thought to buffer against the clinical manifestation of dementia, preserving cognitive function despite accumulating pathology. However, less is known about how CR relates to the capacity to independently perform activities of daily living (ADL), particularly among cognitively unimpaired (CU) older adults. Here, we investigated this association. Methods Baseline data from 1,571 CU participants (mean age: 64.7±7.6; 81.3% female) from the CAN-PROTECT study were analyzed. A composite CR score was derived from education, occupational complexity, and engagement in cognitively stimulating activities. Functional ability was measured using the Standard Assessment of Global Everyday Activities (SAGEA) scale, capturing cognitive, applied cognitive, instrumental, and basic ADL, and mobility. Negative binomial models examined associations between CR and global and domain-specific ADL, adjusting for age, sex, cognition, behaviour, and physical/sensory limitations. Additional models tested the independent contribution of CR components to functional outcomes. Mediation analyses assessed the effect of CR on quality of life (QoL) through ADL abilities. Results Higher CR was associated with lower global ADL impairment (count ratio=0.58, 95%CI: 0.36-0.94, p = 0.027), driven by 49% less impairment in applied cognitive ADL (95%CI: 0.26-0.97, p = 0.038). Among CR domains, education showed the most consistent association with lower impairment across all ADL domains and was indirectly linked to better QoL through improved function. Conclusions CR, particularly education, may play an important role in supporting functional abilities and QoL among CU older adults. Enhancing CR may be a promising avenue to promote functional independence and healthy aging, even in the absence of cognitive impairment.
认知储备（Cognitive reserve， CR）被认为可以缓冲痴呆症的临床表现，在病理积累的情况下保持认知功能。然而，关于CR与独立进行日常生活活动（ADL）的能力之间的关系，特别是在认知未受损（CU）的老年人中，所知甚少。在这里，我们调查了这种关联。方法分析来自CAN-PROTECT研究的1571名CU参与者（平均年龄：64.7±7.6岁，81.3%为女性）的基线数据。综合CR评分来源于教育程度、职业复杂性和参与认知刺激活动。使用全球日常活动标准评估（SAGEA）量表测量功能能力，包括认知、应用认知、工具性和基本ADL以及移动性。负二项模型研究了CR与整体和特定领域ADL之间的关系，调整了年龄、性别、认知、行为和身体/感官限制。其他模型测试了CR成分对功能结果的独立贡献。中介分析通过ADL能力评估CR对生活质量（QoL）的影响。结果较高的CR与较低的整体ADL功能障碍相关（计数比=0.58,95%CI: 0.36-0.94, p = 0.027），应用认知ADL功能障碍减少49% （95%CI: 0.26-0.97, p = 0.038）。在CR域中，教育与所有ADL域中较低的损伤表现出最一致的关联，并通过改善功能间接与更好的生活质量相关。结论CR，特别是教育，可能在CU老年人的功能能力和生活质量支持中起重要作用。即使在没有认知障碍的情况下，增强CR可能是促进功能独立和健康老龄化的有希望的途径。
{"title":"Cognitive reserve and everyday functioning in cognitively unimpaired older adults: evidence from the CAN-PROTECT study","authors":"Maryam Ghahremani, Dylan X Guan, Clive Ballard, Byron Creese, Anne Corbett, Ellie Pickering, Eric E Smith, Zahinoor Ismail","doi":"10.1093/gerona/glag227","DOIUrl":"https://doi.org/10.1093/gerona/glag227","url":null,"abstract":"Background Cognitive reserve (CR) is thought to buffer against the clinical manifestation of dementia, preserving cognitive function despite accumulating pathology. However, less is known about how CR relates to the capacity to independently perform activities of daily living (ADL), particularly among cognitively unimpaired (CU) older adults. Here, we investigated this association. Methods Baseline data from 1,571 CU participants (mean age: 64.7±7.6; 81.3% female) from the CAN-PROTECT study were analyzed. A composite CR score was derived from education, occupational complexity, and engagement in cognitively stimulating activities. Functional ability was measured using the Standard Assessment of Global Everyday Activities (SAGEA) scale, capturing cognitive, applied cognitive, instrumental, and basic ADL, and mobility. Negative binomial models examined associations between CR and global and domain-specific ADL, adjusting for age, sex, cognition, behaviour, and physical/sensory limitations. Additional models tested the independent contribution of CR components to functional outcomes. Mediation analyses assessed the effect of CR on quality of life (QoL) through ADL abilities. Results Higher CR was associated with lower global ADL impairment (count ratio=0.58, 95%CI: 0.36-0.94, p = 0.027), driven by 49% less impairment in applied cognitive ADL (95%CI: 0.26-0.97, p = 0.038). Among CR domains, education showed the most consistent association with lower impairment across all ADL domains and was indirectly linked to better QoL through improved function. Conclusions CR, particularly education, may play an important role in supporting functional abilities and QoL among CU older adults. Enhancing CR may be a promising avenue to promote functional independence and healthy aging, even in the absence of cognitive impairment.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946733","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：