Sarcopenic obesity (SO), a dual condition characterized by the coexistence of sarcopenia and obesity, elevates the risk of metabolic disorders, disability, and mortality to magnitudes exceeding the combined risks of both conditions individually, demonstrating a "super-additive impairment" effect on health. Therefore, this study aims to investigate the mechanisms underlying the pathogenesis and progression of SO. We utilized natural aging mice fed high-fat diets (HFD) to simulate the progression of muscle mass decline observed in geriatric populations and high-calorie diets prevalent in modern societies, creating an SO animal model with exceptional clinical relevance. Our study demonstrates that HFD exacerbates age-related reductions in muscle mass, accompanied by decreased physical performance and increased lipid accumulation. Importantly, HFD-induced lipid infiltration emerges as a significant contributor to the further decline in skeletal muscle mass in SO mice, and the Nrf2/Prdx6 pathway is a mechanism regulating this factor. Aerobic exercise, a safe and reliable means for older adults, is particularly effective for fat loss and muscle maintenance. In our study, aerobic exercise effectively alleviated the detrimental effects of HFD on muscle health in aging mice. Mechanistic studies revealed that Nrf2 and Prdx6 protein expression was significantly suppressed in vivo by HFD and in vitro following palmitic acid (PA) exposure. Conversely, overexpression of Nrf2 and Prdx6 in vitro was able to mimic the protective effects of aerobic exercise. Our results indicate that the Nrf2/Prdx6 pathway plays a crucial role in counteracting muscle mass loss induced by HFD and may underlie beneficial effects of aerobic exercise on skeletal muscle.
{"title":"High-fat diet exacerbates skeletal muscle mass loss via Nrf2/Prdx6 pathway in sarcopenic obesity mice.","authors":"Danni Wang,Xinyue Zheng,Yang Zhu,Wen Zhang,Sujuan Liu,Yanmei Niu","doi":"10.1093/gerona/glaf271","DOIUrl":"https://doi.org/10.1093/gerona/glaf271","url":null,"abstract":"Sarcopenic obesity (SO), a dual condition characterized by the coexistence of sarcopenia and obesity, elevates the risk of metabolic disorders, disability, and mortality to magnitudes exceeding the combined risks of both conditions individually, demonstrating a \"super-additive impairment\" effect on health. Therefore, this study aims to investigate the mechanisms underlying the pathogenesis and progression of SO. We utilized natural aging mice fed high-fat diets (HFD) to simulate the progression of muscle mass decline observed in geriatric populations and high-calorie diets prevalent in modern societies, creating an SO animal model with exceptional clinical relevance. Our study demonstrates that HFD exacerbates age-related reductions in muscle mass, accompanied by decreased physical performance and increased lipid accumulation. Importantly, HFD-induced lipid infiltration emerges as a significant contributor to the further decline in skeletal muscle mass in SO mice, and the Nrf2/Prdx6 pathway is a mechanism regulating this factor. Aerobic exercise, a safe and reliable means for older adults, is particularly effective for fat loss and muscle maintenance. In our study, aerobic exercise effectively alleviated the detrimental effects of HFD on muscle health in aging mice. Mechanistic studies revealed that Nrf2 and Prdx6 protein expression was significantly suppressed in vivo by HFD and in vitro following palmitic acid (PA) exposure. Conversely, overexpression of Nrf2 and Prdx6 in vitro was able to mimic the protective effects of aerobic exercise. Our results indicate that the Nrf2/Prdx6 pathway plays a crucial role in counteracting muscle mass loss induced by HFD and may underlie beneficial effects of aerobic exercise on skeletal muscle.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"149 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746711","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}
BACKGROUNDFrailty is a key intervention target for older adults with cardiovascular-kidney-metabolic (CKM) syndrome. Evidence suggests that the triglyceride glucose (TyG) index and body roundness index (BRI) are associated with frailty; however, the predictive value of their combination (TyG-BRI) remains unclear.METHODSWe analyzed data from 3,687 middle-aged and older adults with CKM syndrome in the China Health and Retirement Longitudinal Study (CHARLS, 2011 to 2020). The frailty index serving as the outcome variable was constructed based on 30 multidimensional health deficit items. The primary exposure, the TyG-BRI index, was calculated as the product of the TyG index and the BRI. Latent growth mixture modeling (LGMM) was employed to identify frailty trajectories. Multivariable adjusted logistic regression was conducted to explore the association between TyG-BRI and frailty trajectories. Subgroup analyses were performed to elucidate the interactions among these factors further.RESULTSThree distinct frailty trajectories emerged: pre-frailty to frailty deterioration (18.8%), persistent frailty (53.7%), and pre-frailty transition to health (27.4%). The highest TyG-BRI quartile was associated with a higher risk of pre-frailty to frailty deterioration than the lowest quartile (OR = 2.229, 95% CI: 1.137-4.367). Subgroup analysis indicated a significant interaction between age and the association of TyG-BRI with frailty trajectories (P = 0.041), suggesting the need for age-specific intervention strategies.CONCLUSIONThe TyG-BRI may be an early metabolic biomarker for pre-frailty to frailty deterioration in individuals with CKM syndrome, particularly in older adults. These findings suggest a critical intervention window targeting metabolic dysregulation during the pre-frailty stage.
{"title":"Associations between the triglyceride glucose-body roundness index and frailty trajectory in populations with Cardiovascular-Kidney-Metabolic syndrome: A nationwide prospective cohort study.","authors":"Zhongmin Fu,Shulin Song,Yan Ji,Lisi Duan,Ziyan Wang,Yue Chen,Yinning Guo,Kang Zhao,Xinyi Xu,Changqing Wang,Qin Xu","doi":"10.1093/gerona/glaf273","DOIUrl":"https://doi.org/10.1093/gerona/glaf273","url":null,"abstract":"BACKGROUNDFrailty is a key intervention target for older adults with cardiovascular-kidney-metabolic (CKM) syndrome. Evidence suggests that the triglyceride glucose (TyG) index and body roundness index (BRI) are associated with frailty; however, the predictive value of their combination (TyG-BRI) remains unclear.METHODSWe analyzed data from 3,687 middle-aged and older adults with CKM syndrome in the China Health and Retirement Longitudinal Study (CHARLS, 2011 to 2020). The frailty index serving as the outcome variable was constructed based on 30 multidimensional health deficit items. The primary exposure, the TyG-BRI index, was calculated as the product of the TyG index and the BRI. Latent growth mixture modeling (LGMM) was employed to identify frailty trajectories. Multivariable adjusted logistic regression was conducted to explore the association between TyG-BRI and frailty trajectories. Subgroup analyses were performed to elucidate the interactions among these factors further.RESULTSThree distinct frailty trajectories emerged: pre-frailty to frailty deterioration (18.8%), persistent frailty (53.7%), and pre-frailty transition to health (27.4%). The highest TyG-BRI quartile was associated with a higher risk of pre-frailty to frailty deterioration than the lowest quartile (OR = 2.229, 95% CI: 1.137-4.367). Subgroup analysis indicated a significant interaction between age and the association of TyG-BRI with frailty trajectories (P = 0.041), suggesting the need for age-specific intervention strategies.CONCLUSIONThe TyG-BRI may be an early metabolic biomarker for pre-frailty to frailty deterioration in individuals with CKM syndrome, particularly in older adults. These findings suggest a critical intervention window targeting metabolic dysregulation during the pre-frailty stage.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746709","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}
Silvia Vittoria Cracas,Rose Anne Kenny,Siobhan Scarlett,Cathal Mccrory
BACKGROUNDFrailty is a critical public health issue in aging populations, linked to increased disability, hospitalization, and mortality. While biological and clinical risk factors are well established, less is known about how psychological traits, particularly personality, influence frailty development and 'get outside the skin' to affect health.METHODSUsing data from Wave 3 (2014-2015) of The Irish Longitudinal Study on Ageing (TILDA), we examined associations between the Big Five personality traits and frailty among 2,146 community-dwelling older adults. Personality was assessed with the 60-item NEO-FFI-R. Frailty was measured both subjectively (self-reported deficits) and objectively with clinical and functional indicators matched to the subjective items to minimize reporting bias. Mediation analyses explored psychosocial and behavioral pathways, including stress, social support, resilience, smoking, and body composition.RESULTSNeuroticism was consistently associated with higher frailty, especially on the subjective index. In contrast, openness and extraversion were linked to lower objective frailty. Perceived stress emerged as the strongest mediator of the neuroticism-frailty link, followed by WHR and smoking. For openness, resilience and WHR contributed modestly to its protective effect; extraversion's benefit was primarily mediated by social support. Distinct mediation patterns emerged across personality traits and frailty types, underscoring the complexity of these relationships.CONCLUSIONPersonality traits, particularly neuroticism, openness, and extraversion, are meaningfully related to frailty via psychological and behavioral mechanisms. Findings support the integration of psychosocial resources into frailty prevention and healthy aging strategies.
{"title":"Personality Traits Influence Frailty in Older Adults through Health Behaviours and Psychosocial Resources.","authors":"Silvia Vittoria Cracas,Rose Anne Kenny,Siobhan Scarlett,Cathal Mccrory","doi":"10.1093/gerona/glaf274","DOIUrl":"https://doi.org/10.1093/gerona/glaf274","url":null,"abstract":"BACKGROUNDFrailty is a critical public health issue in aging populations, linked to increased disability, hospitalization, and mortality. While biological and clinical risk factors are well established, less is known about how psychological traits, particularly personality, influence frailty development and 'get outside the skin' to affect health.METHODSUsing data from Wave 3 (2014-2015) of The Irish Longitudinal Study on Ageing (TILDA), we examined associations between the Big Five personality traits and frailty among 2,146 community-dwelling older adults. Personality was assessed with the 60-item NEO-FFI-R. Frailty was measured both subjectively (self-reported deficits) and objectively with clinical and functional indicators matched to the subjective items to minimize reporting bias. Mediation analyses explored psychosocial and behavioral pathways, including stress, social support, resilience, smoking, and body composition.RESULTSNeuroticism was consistently associated with higher frailty, especially on the subjective index. In contrast, openness and extraversion were linked to lower objective frailty. Perceived stress emerged as the strongest mediator of the neuroticism-frailty link, followed by WHR and smoking. For openness, resilience and WHR contributed modestly to its protective effect; extraversion's benefit was primarily mediated by social support. Distinct mediation patterns emerged across personality traits and frailty types, underscoring the complexity of these relationships.CONCLUSIONPersonality traits, particularly neuroticism, openness, and extraversion, are meaningfully related to frailty via psychological and behavioral mechanisms. Findings support the integration of psychosocial resources into frailty prevention and healthy aging strategies.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746714","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}
BACKGROUNDThis study investigated domain-specific associations between osteosarcopenia, defined as the coexistence of osteopenia or osteoporosis with low handgrip strength (HGS), and cognitive function in a cohort of older adults (≥65 years) from the 2011-2014 cycles of the National Health and Nutrition Examination Survey (NHANES).METHODSOsteosarcopenia was defined by the presence of osteopenia or osteoporosis (based on femoral T-scores) combined with low HGS. Cognitive function was assessed using the Digit Symbol Substitution, Delayed Recall, Intrusion Word Count, and Animal Fluency tests. Linear regression models examined the bidirectional associations between osteosarcopenia and cognitive performance.RESULTSThe sample included 1355 older adults (mean age 70.3 ± 6.9 years; 57% women). Compared to participants with osteoporosis alone, those with coexisting osteoporosis and low HGS performed significantly worse on the Digit Symbol Test (β = -9.6; 95% CI -16.7 - -2.5; p = 0.01) and had similar Delayed Recall scores (β -0.6; 95% CI -1.3-0.1; p = 0.10). In participants with osteopenia and low HGS, a significant association was observed only for the Digit Symbol Test (β -8.1; 95% CI -13.4 - -2.7; p < 0.01). No significant associations were found for osteoporosis or osteopenia in isolation.CONCLUSIONSOsteosarcopenia, particularly the combination of reduced bone mineral density and low muscle strength, is associated with poorer performance in selected cognitive domains, especially processing speed and memory. These findings underscore the potential value of integrated screening approaches and multidimensional interventions targeting musculoskeletal and cognitive health in aging populations.
背景：本研究调查了2011-2014年国家健康与营养调查（NHANES）中老年人（≥65岁）队列中骨量减少症（定义为骨质减少或骨质疏松症与低握力（HGS）共存）与认知功能之间的特定领域相关性。方法骨质减少症的定义是存在骨质减少或骨质疏松症（基于股骨t评分）并伴有低HGS。使用数字符号替代、延迟回忆、入侵词计数和动物流畅性测试来评估认知功能。线性回归模型检验了骨骼肌减少症与认知能力之间的双向关联。结果老年人1355例，平均年龄70.3±6.9岁，女性占57%。与单独患有骨质疏松症的参与者相比，合并骨质疏松症和低HGS的参与者在数字符号测试中的表现明显较差（β = -9.6; 95% CI -16.7 - -2.5; p = 0.01），延迟回忆得分相似（β -0.6; 95% CI -1.3-0.1; p = 0.10）。在骨质减少和低HGS的参与者中，仅在数字符号测试中观察到显著关联（β -8.1; 95% CI -13.4 - -2.7; p < 0.01）。没有发现骨质疏松或骨质减少单独的显著关联。结论骨骼肌减少症，特别是骨密度降低和肌肉力量低下，与某些认知领域的表现较差有关，特别是处理速度和记忆。这些发现强调了针对老年人群肌肉骨骼和认知健康的综合筛查方法和多维干预的潜在价值。
{"title":"Associations between osteosarcopenia and cognitive function in community-dwelling older adults: evidence from a US cohort.","authors":"Konstantinos Prokopidis,Stefano Cacciatore,Nicola Veronese,Gustavo Duque,Mathias Schlögl","doi":"10.1093/gerona/glaf276","DOIUrl":"https://doi.org/10.1093/gerona/glaf276","url":null,"abstract":"BACKGROUNDThis study investigated domain-specific associations between osteosarcopenia, defined as the coexistence of osteopenia or osteoporosis with low handgrip strength (HGS), and cognitive function in a cohort of older adults (≥65 years) from the 2011-2014 cycles of the National Health and Nutrition Examination Survey (NHANES).METHODSOsteosarcopenia was defined by the presence of osteopenia or osteoporosis (based on femoral T-scores) combined with low HGS. Cognitive function was assessed using the Digit Symbol Substitution, Delayed Recall, Intrusion Word Count, and Animal Fluency tests. Linear regression models examined the bidirectional associations between osteosarcopenia and cognitive performance.RESULTSThe sample included 1355 older adults (mean age 70.3 ± 6.9 years; 57% women). Compared to participants with osteoporosis alone, those with coexisting osteoporosis and low HGS performed significantly worse on the Digit Symbol Test (β = -9.6; 95% CI -16.7 - -2.5; p = 0.01) and had similar Delayed Recall scores (β -0.6; 95% CI -1.3-0.1; p = 0.10). In participants with osteopenia and low HGS, a significant association was observed only for the Digit Symbol Test (β -8.1; 95% CI -13.4 - -2.7; p < 0.01). No significant associations were found for osteoporosis or osteopenia in isolation.CONCLUSIONSOsteosarcopenia, particularly the combination of reduced bone mineral density and low muscle strength, is associated with poorer performance in selected cognitive domains, especially processing speed and memory. These findings underscore the potential value of integrated screening approaches and multidimensional interventions targeting musculoskeletal and cognitive health in aging populations.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"157 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746705","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}
Cognitive impairment is a significant health concern in aging populations, but the interplay between biological aging, lifestyle factors, and genetic susceptibility remains unclear. This study examined whether accelerated biological aging is associated with cognitive impairment, whether lifestyle modifies this association, and how genetic background influences these relationships in Chinese older adults. In this cross-sectional study (2022-2023), 7,033 participants from southwestern China were included. Accelerated biological aging was calculated as the residual difference between biological age (based on 10 biomarkers) and chronological age. Lifestyle was assessed via a composite index (smoking, alcohol, physical activity, diet, sleep). Cognitive function was measured using the Chinese Mini-Mental State Examination (C-MMSE), and genetic risk was evaluated through polygenic scores and APOE ε4 status. Linear and logistic regression models assessed associations between accelerated aging and cognition. Accelerated biological aging was associated with lower MMSE scores (β = -0.243, 95% CI: -0.354, -0.133) and higher cognitive impairment prevalence (OR = 1.098, 95% CI: 1.040, 1.158). An unhealthy lifestyle exacerbated cognitive impairment in biologically older individuals (RERI = 0.25). Those with both accelerated aging and unhealthy lifestyle had the lowest MMSE scores (β = -1.424, 95% CI: -1.846, -1.003) and highest odds of cognitive impairment (OR = 1.467, 95% CI: 1.194, 1.803). These effects were consistent across all genetic background subgroups. Accelerated aging was associated with lower cognitive function, especially in individuals with unhealthy lifestyles, regardless of genetic susceptibility. This highlights lifestyle modification as a potential intervention target for aging-related cognitive impairment.
{"title":"Interplay of Accelerated Biological Aging, Lifestyle Factors, and Genetic Susceptibility in Cognitive Function: A Community Study.","authors":"Tianpei Ma,Xin Chen,Qingwen Zhao,Xinyin Xu,Xingyu Zhang,Xiaoxue Liu,Diji Zhuoma,Mengjie Hu,Haiyu Yan,Lei Lin,Ke Jiang,Xinyang Dui,Xunying Zhao,Xueyao Wu,Jinyu Xiao,Xia Jiang,Tao Zhang,Mengyu Fan,Lu Long,Ying Deng,Jiaqiang Liao,Jiayuan Li","doi":"10.1093/gerona/glaf277","DOIUrl":"https://doi.org/10.1093/gerona/glaf277","url":null,"abstract":"Cognitive impairment is a significant health concern in aging populations, but the interplay between biological aging, lifestyle factors, and genetic susceptibility remains unclear. This study examined whether accelerated biological aging is associated with cognitive impairment, whether lifestyle modifies this association, and how genetic background influences these relationships in Chinese older adults. In this cross-sectional study (2022-2023), 7,033 participants from southwestern China were included. Accelerated biological aging was calculated as the residual difference between biological age (based on 10 biomarkers) and chronological age. Lifestyle was assessed via a composite index (smoking, alcohol, physical activity, diet, sleep). Cognitive function was measured using the Chinese Mini-Mental State Examination (C-MMSE), and genetic risk was evaluated through polygenic scores and APOE ε4 status. Linear and logistic regression models assessed associations between accelerated aging and cognition. Accelerated biological aging was associated with lower MMSE scores (β = -0.243, 95% CI: -0.354, -0.133) and higher cognitive impairment prevalence (OR = 1.098, 95% CI: 1.040, 1.158). An unhealthy lifestyle exacerbated cognitive impairment in biologically older individuals (RERI = 0.25). Those with both accelerated aging and unhealthy lifestyle had the lowest MMSE scores (β = -1.424, 95% CI: -1.846, -1.003) and highest odds of cognitive impairment (OR = 1.467, 95% CI: 1.194, 1.803). These effects were consistent across all genetic background subgroups. Accelerated aging was associated with lower cognitive function, especially in individuals with unhealthy lifestyles, regardless of genetic susceptibility. This highlights lifestyle modification as a potential intervention target for aging-related cognitive impairment.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746712","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}
Jatupol Kositsawat,George A Kuchel,Kelin Zhong,Shangshu Zhao,Richard H Fortinsky,Chia-Ling Kuo
BACKGROUNDAging is multifactorial, yet aging research emphasizes independent risk factors. Endocrine and inflammatory factors have been linked to opposing and synergistic associations with suboptimal aging.METHODSGiven the importance of multifactorial nonlinear approaches, we interrogated interactions of vitamin D deficiency (VDD; 25-hydroxyvitamin D (25(OH)D) < 20 ng/mL) and high C-reactive protein (CRP) levels (≥ 2.6 mg/L; the third quartile among the included sample) with biological aging acceleration (BAA) in 313,444 UK Biobank participants. BAA (chronological < expected BA) was derived from PhenoAgeAccel (Phenotypic age (PhenoAge) adjusted for chronological age and covariates). 25(OH)D and CRP levels were linked to BAA using restricted cubic spline regression models.RESULTSWe observed moderation effects of CRP on VDD-BAA association, and that of 25(OH)D on the high CRP-BAA association. PhenoAgeAccel values for participants with VDD were 0.576 (95% CI 0.570 to 0.583) years at CRP z-score 2 compared to 0.121 (95% CI 0.120 to 0.122) years at CRP z-score 0. In contrast to a U-shaped relationship between 25(OH)D and BAA, all higher CRP levels were more strongly associated with higher BAA. Association between VDD and BAA was greater in participants with higher CRP levels, yet participants with high CRP levels showed similar BAA regardless of vitamin D levels.CONCLUSIONSOur findings illustrate these risk factors' nonlinear and interactive nature, highlighting the importance of targeting resulting heterogeneity in aging trajectories by developing more targeted interventions via Precision Gerontology. Approaches may include interventions targeting inflammation in individuals with both VDD and inflammation.
衰老是一个多因素的过程，但衰老研究强调的是独立的危险因素。内分泌和炎症因素与亚理想衰老有拮抗和协同作用。方法考虑到多因素非线性方法的重要性，我们在313444名英国生物银行参与者中研究了维生素D缺乏症(VDD; 25(OH)D) < 20 ng/mL)和高c反应蛋白（CRP）水平（≥2.6 mg/L；在所包括样本中的第三个四分位数）与生物衰老加速（BAA）的相互作用。BAA（实际年龄<预期年龄）来源于PhenoAgeAccel（根据实际年龄和协变量调整的表型年龄（PhenoAge））。25(OH)D和CRP水平与BAA使用限制三次样条回归模型相关联。结果我们观察到CRP对VDD-BAA关联的调节作用，以及25(OH)D对高CRP- baa关联的调节作用。VDD患者的PhenoAgeAccel值在CRP z-score 2时为0.576 （95% CI 0.570至0.583）年，而在CRP z-score 0时为0.121 （95% CI 0.120至0.122）年。与25(OH)D和BAA呈u型关系相反，所有较高的CRP水平都与较高的BAA密切相关。在CRP水平较高的参与者中，VDD和BAA之间的关联更大，然而，无论维生素D水平如何，高CRP水平的参与者表现出相似的BAA。结论我们的研究结果说明了这些风险因素的非线性和相互作用性质，强调了通过精确老年学开发更有针对性的干预措施来针对衰老轨迹的异质性的重要性。方法可能包括针对VDD和炎症个体的炎症干预。
{"title":"The nonlinear U-shaped association between vitamin D deficiency and biological aging acceleration is enhanced in individuals with higher inflammation levels.","authors":"Jatupol Kositsawat,George A Kuchel,Kelin Zhong,Shangshu Zhao,Richard H Fortinsky,Chia-Ling Kuo","doi":"10.1093/gerona/glaf272","DOIUrl":"https://doi.org/10.1093/gerona/glaf272","url":null,"abstract":"BACKGROUNDAging is multifactorial, yet aging research emphasizes independent risk factors. Endocrine and inflammatory factors have been linked to opposing and synergistic associations with suboptimal aging.METHODSGiven the importance of multifactorial nonlinear approaches, we interrogated interactions of vitamin D deficiency (VDD; 25-hydroxyvitamin D (25(OH)D) < 20 ng/mL) and high C-reactive protein (CRP) levels (≥ 2.6 mg/L; the third quartile among the included sample) with biological aging acceleration (BAA) in 313,444 UK Biobank participants. BAA (chronological < expected BA) was derived from PhenoAgeAccel (Phenotypic age (PhenoAge) adjusted for chronological age and covariates). 25(OH)D and CRP levels were linked to BAA using restricted cubic spline regression models.RESULTSWe observed moderation effects of CRP on VDD-BAA association, and that of 25(OH)D on the high CRP-BAA association. PhenoAgeAccel values for participants with VDD were 0.576 (95% CI 0.570 to 0.583) years at CRP z-score 2 compared to 0.121 (95% CI 0.120 to 0.122) years at CRP z-score 0. In contrast to a U-shaped relationship between 25(OH)D and BAA, all higher CRP levels were more strongly associated with higher BAA. Association between VDD and BAA was greater in participants with higher CRP levels, yet participants with high CRP levels showed similar BAA regardless of vitamin D levels.CONCLUSIONSOur findings illustrate these risk factors' nonlinear and interactive nature, highlighting the importance of targeting resulting heterogeneity in aging trajectories by developing more targeted interventions via Precision Gerontology. Approaches may include interventions targeting inflammation in individuals with both VDD and inflammation.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746710","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}
Laboratory inbred strains respond strongly to dietary restriction (DR), whereas genetically diverse populations may not experience comparable benefits. The exceptionally short-lived fish, Nothobranchius furzeri, offers several genetically distinct captive populations; however, only the severely inbred GRZ strain has been tested for DR effects. Here, individually kept males (N = 111) of the outbred MZCS 222 strain of N. furzeri were assigned to 1/high-protein diet and two DR forms: 2/low-protein (isocaloric to high-protein but half the protein concentration), or 3/caloric-restriction (half the dose of HP at the feeding time). Neither form of DR significantly extended the lifespan of N. furzeri males. The limited efficacy of protein and caloric restriction in outbred N. furzeri may stem from insensitivity to these forms of DR or from the genetic diversity of the strain in comparison to earlier reported life extension through intermittent fasting in the inbred GRZ strain.
实验室自交系对饮食限制（DR）反应强烈，而遗传多样性种群可能没有类似的益处。这种特别短命的鱼，狐尾Nothobranchius furzeri，提供了几个基因上不同的圈养种群；然而，只有严重自交系的GRZ菌株进行了DR效应测试。在这里，单独饲养的MZCS 222型furzeri N = 111只雄虫（N = 111）被分配到1/高蛋白饮食和两种DR形式：2/低蛋白（等量热量到高蛋白，但蛋白质浓度减半），或3/热量限制（饲喂时HP剂量的一半）。两种形式的DR均不能显著延长狐尾扁虱雄性的寿命。在近交系中限制蛋白质和热量的有限效果可能源于对这些DR形式的不敏感，或者与早期报道的近交系GRZ菌株通过间歇性禁食延长寿命相比，该菌株的遗传多样性。
{"title":"Neither caloric nor protein restriction increases the male lifespan of outbred short-lived fish.","authors":"Jakub Žák,Martin Reichard","doi":"10.1093/gerona/glaf278","DOIUrl":"https://doi.org/10.1093/gerona/glaf278","url":null,"abstract":"Laboratory inbred strains respond strongly to dietary restriction (DR), whereas genetically diverse populations may not experience comparable benefits. The exceptionally short-lived fish, Nothobranchius furzeri, offers several genetically distinct captive populations; however, only the severely inbred GRZ strain has been tested for DR effects. Here, individually kept males (N = 111) of the outbred MZCS 222 strain of N. furzeri were assigned to 1/high-protein diet and two DR forms: 2/low-protein (isocaloric to high-protein but half the protein concentration), or 3/caloric-restriction (half the dose of HP at the feeding time). Neither form of DR significantly extended the lifespan of N. furzeri males. The limited efficacy of protein and caloric restriction in outbred N. furzeri may stem from insensitivity to these forms of DR or from the genetic diversity of the strain in comparison to earlier reported life extension through intermittent fasting in the inbred GRZ strain.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746713","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}
Johanna Pöyhönen, Hanna-Maria Roitto, Jenni Lehtisalo, Esko Levälahti, Timo Strandberg, Miia Kivipelto, Jenni Kulmala, Riitta Antikainen, Hilkka Soininen, Jaakko Tuomilehto, Tiina Laatikainen, Tiia Ngandu
Background Cognitive frailty (CF), a condition with physical frailty and mild cognitive impairment (MCI) without dementia, is potentially reversible and linked to adverse outcomes. We aimed to investigate the impact of a multidomain lifestyle intervention on temporal dynamics of CF in older adults at risk of dementia. Methods In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), 1259 participants, aged 60–77, were randomized to a 2-year multidomain lifestyle intervention or standard health advice. Frailty was defined by modified Fried phenotype and MCI by lowest quintile in Neuropsychological Test Battery z score. Having pre-frailty/frailty and MCI was classified as CF. Transition probabilities and predictiveness of CF by four different baseline groups (healthy; MCI; pre-frail/frail; CF) were examined using multinomial logistic regression. Results At baseline, 219 participants (18%) had CF. The risk for developing CF at two years was higher in the control group (RR 1.88, p = 0.003). The intervention effect was not modified by baseline CF (p = 0.493). Reversal from CF to no-CF group was more likely in the intervention group, and progression to or persisting with CF in the control group. Compared with healthy participants (n = 401) at baseline, MCI group (n = 244) had RR of 5.10, pre-frail/frail (n = 336) of 3.06, and CF of 30.61 for having CF at two years, with no difference between MCI and pre-frail/frail groups (p = 0.116). Conclusions The two-year multidomain lifestyle intervention was effective in preventing and reversing CF. Participants with MCI or pre-frailty/frailty were both at increased risk for CF compared with healthy.
{"title":"Impact of Multidomain Lifestyle Intervention on Dynamics of Cognitive Frailty: Post-hoc Analysis of the FINGER Trial","authors":"Johanna Pöyhönen, Hanna-Maria Roitto, Jenni Lehtisalo, Esko Levälahti, Timo Strandberg, Miia Kivipelto, Jenni Kulmala, Riitta Antikainen, Hilkka Soininen, Jaakko Tuomilehto, Tiina Laatikainen, Tiia Ngandu","doi":"10.1093/gerona/glaf275","DOIUrl":"https://doi.org/10.1093/gerona/glaf275","url":null,"abstract":"Background Cognitive frailty (CF), a condition with physical frailty and mild cognitive impairment (MCI) without dementia, is potentially reversible and linked to adverse outcomes. We aimed to investigate the impact of a multidomain lifestyle intervention on temporal dynamics of CF in older adults at risk of dementia. Methods In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), 1259 participants, aged 60–77, were randomized to a 2-year multidomain lifestyle intervention or standard health advice. Frailty was defined by modified Fried phenotype and MCI by lowest quintile in Neuropsychological Test Battery z score. Having pre-frailty/frailty and MCI was classified as CF. Transition probabilities and predictiveness of CF by four different baseline groups (healthy; MCI; pre-frail/frail; CF) were examined using multinomial logistic regression. Results At baseline, 219 participants (18%) had CF. The risk for developing CF at two years was higher in the control group (RR 1.88, p = 0.003). The intervention effect was not modified by baseline CF (p = 0.493). Reversal from CF to no-CF group was more likely in the intervention group, and progression to or persisting with CF in the control group. Compared with healthy participants (n = 401) at baseline, MCI group (n = 244) had RR of 5.10, pre-frail/frail (n = 336) of 3.06, and CF of 30.61 for having CF at two years, with no difference between MCI and pre-frail/frail groups (p = 0.116). Conclusions The two-year multidomain lifestyle intervention was effective in preventing and reversing CF. Participants with MCI or pre-frailty/frailty were both at increased risk for CF compared with healthy.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759570","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}
Manuel E Hernandez, Robert W Motl, Frederick W Foley, Meltem Izzetoglu, Mark Wagshul, Roee Holtzer
Background Falls and gait variability are prevalent in older adults with and without multiple sclerosis. Gait variability has been associated with an increased likelihood of reporting falls in older adults, yet its prediction of falls in older adults with multiple sclerosis remains unclear. Methods We examined whether gait variability measured under single- and dual-task walking conditions predicted falls during longitudinal follow-up in older adults with multiple sclerosis (OAMS) and healthy older adults (HOA). HOA (n = 106, mean age=69 years) and OAMS (n = 95, mean age=65 years) completed a single and dual-task walking paradigm and reported falls during a longitudinal follow-up. Gait variability was measured using an instrumented walkway. Results Cox-regression models indicated that larger coefficients of variation (CVs) of dual-task-walk stride length (HR = 1.04, p = 0.017), dual-task-walk swing time (HR = 1.03, p = 0.044), and single-task-walk swing time (HR = 1.05, p < 0.001) were significantly associated with increased hazards of incident falls, even after adjustment. Cohort-stratified cox-regression models with adjustment showed that larger single-task-walk swing time CV was associated with a higher hazard of incident falls in HOA (HR = 1.10, p = 0.028), while larger CVs in dual-task-walk stride velocity (HR = 1.04, p = 0.017), stride length (HR = 1.06, p = 0.016), and swing time (HR = 1.05, p = 0.018) were significantly associated with a higher hazard of incident falls in OAMS. Conclusions Findings suggest that greater gait variability predicts increased fall risk in OAMS and HOA participants, with a 1% increase in CV associated with a 4-10% fall hazard increase. However, walking condition influenced this association with single-task-walk variability being predictive in HOA, while dual-task-walk variability is more predictive in OAMS.
背景：跌倒和步态变异性在有或没有多发性硬化症的老年人中很普遍。步态变异性与老年人报告跌倒的可能性增加有关，但其对多发性硬化症老年人跌倒的预测仍不清楚。方法：我们研究了在单任务和双任务步行条件下测量的步态变异性是否能预测多发性硬化症（OAMS）和健康老年人（HOA）的纵向随访。HOA （n = 106，平均年龄=69岁）和OAMS （n = 95，平均年龄=65岁）完成了单任务和双任务步行范式，并在纵向随访中报告跌倒。步态变异性测量使用仪器人行道。结果cox回归模型显示，即使经过调整，双任务步行步幅（HR = 1.04, p = 0.017）、双任务步行摆动时间（HR = 1.03, p = 0.044）和单任务步行摆动时间（HR = 1.05, p < 0.001）的较大变异系数（cv）也与意外跌倒风险增加显著相关。校正后的队列分层cox回归模型显示，较大的单任务步行摆动时间CV与较高的HOA事件跌倒风险相关（HR = 1.10, p = 0.028），而较大的双任务步行步幅CV （HR = 1.04, p = 0.017）、步幅长度CV （HR = 1.06, p = 0.016）和摆动时间CV （HR = 1.05, p = 0.018）与较高的OAMS事件跌倒风险相关。研究结果表明，更大的步态变异性预示着OAMS和HOA参与者跌倒风险增加，CV增加1%与跌倒风险增加4-10%相关。然而，步行条件影响了这种关联，单任务步行变异性在HOA中具有预测性，而双任务步行变异性在OAMS中更具预测性。
{"title":"Gait variability predicts falls in older adults with multiple sclerosis","authors":"Manuel E Hernandez, Robert W Motl, Frederick W Foley, Meltem Izzetoglu, Mark Wagshul, Roee Holtzer","doi":"10.1093/gerona/glaf269","DOIUrl":"https://doi.org/10.1093/gerona/glaf269","url":null,"abstract":"Background Falls and gait variability are prevalent in older adults with and without multiple sclerosis. Gait variability has been associated with an increased likelihood of reporting falls in older adults, yet its prediction of falls in older adults with multiple sclerosis remains unclear. Methods We examined whether gait variability measured under single- and dual-task walking conditions predicted falls during longitudinal follow-up in older adults with multiple sclerosis (OAMS) and healthy older adults (HOA). HOA (n = 106, mean age=69 years) and OAMS (n = 95, mean age=65 years) completed a single and dual-task walking paradigm and reported falls during a longitudinal follow-up. Gait variability was measured using an instrumented walkway. Results Cox-regression models indicated that larger coefficients of variation (CVs) of dual-task-walk stride length (HR = 1.04, p = 0.017), dual-task-walk swing time (HR = 1.03, p = 0.044), and single-task-walk swing time (HR = 1.05, p &lt; 0.001) were significantly associated with increased hazards of incident falls, even after adjustment. Cohort-stratified cox-regression models with adjustment showed that larger single-task-walk swing time CV was associated with a higher hazard of incident falls in HOA (HR = 1.10, p = 0.028), while larger CVs in dual-task-walk stride velocity (HR = 1.04, p = 0.017), stride length (HR = 1.06, p = 0.016), and swing time (HR = 1.05, p = 0.018) were significantly associated with a higher hazard of incident falls in OAMS. Conclusions Findings suggest that greater gait variability predicts increased fall risk in OAMS and HOA participants, with a 1% increase in CV associated with a 4-10% fall hazard increase. However, walking condition influenced this association with single-task-walk variability being predictive in HOA, while dual-task-walk variability is more predictive in OAMS.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"226 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730710","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}
Aitana Vázquez-Fernández,Humberto Yévenes-Briones,Ana Baylin,Francisco F Caballero,Esther Lopez-Garcia
BACKGROUNDMultimorbidity is a major determinant of lifespan in older adults. We aimed to examine the association between overall, healthy and unhealthy Low-Carbohydrate diets (LCD) and Low-Fat diets (LFD) with the incidence of multimorbidity.METHODS112,710 individuals (40-70 years) from the UK Biobank were included. Food consumption was assessed using up to five 24-hour dietary recalls. LCD and LFD scores were calculated based on macronutrient quality. We calculated three versions of each score-overall, healthy and unhealthy. Multimorbidity was defined as the coexistence of ≥ 2 of nine chronic diseases, including cancer, chronic obstructive pulmonary disease, dementia, Parkinson's disease, stroke, depression, osteoarthritis, diabetes, and coronary heart disease.RESULTSThere were 8,387 individuals with multimorbidity during a median follow-up of 10.7-years. Overall LCD and LFD scores were not associated with higher multimorbidity risk. There was a higher multimorbidity risk for individuals in the highest quintile (Q5) of unhealthy LCD vs. lowest quintile (Q1) [fully adjusted hazard ratio (HR): 1.07, 95%CI: 1.01, 1.15, p-trend=.16] overall as well as among non-tobacco smokers [1.11 (1.00, 1.23, p-trend=.09]. The unhealthy LFD score was associated with multimorbidity overall [1.07 (1.00, 1.14), p-trend=.07] and never-smokers [1.12 (1.01, 1.24); p-trend=.01]. Healthy scores results were less consistent. The plant protein component had an inverse association with incident multimorbidity risk, whereas the low-quality-fat and animal protein components were each associated with higher risk of multimorbidity.CONCLUSIONDiet scores defined only by the total amount of carbohydrates or fat were not associated with risk of multimorbidity. Unhealthy diet scores including low-quality macronutrients and animal protein were associated with increased risk of multimorbidity.
{"title":"Macronutrient content and quality, and risk of multimorbidity in the UK biobank.","authors":"Aitana Vázquez-Fernández,Humberto Yévenes-Briones,Ana Baylin,Francisco F Caballero,Esther Lopez-Garcia","doi":"10.1093/gerona/glaf267","DOIUrl":"https://doi.org/10.1093/gerona/glaf267","url":null,"abstract":"BACKGROUNDMultimorbidity is a major determinant of lifespan in older adults. We aimed to examine the association between overall, healthy and unhealthy Low-Carbohydrate diets (LCD) and Low-Fat diets (LFD) with the incidence of multimorbidity.METHODS112,710 individuals (40-70 years) from the UK Biobank were included. Food consumption was assessed using up to five 24-hour dietary recalls. LCD and LFD scores were calculated based on macronutrient quality. We calculated three versions of each score-overall, healthy and unhealthy. Multimorbidity was defined as the coexistence of ≥ 2 of nine chronic diseases, including cancer, chronic obstructive pulmonary disease, dementia, Parkinson's disease, stroke, depression, osteoarthritis, diabetes, and coronary heart disease.RESULTSThere were 8,387 individuals with multimorbidity during a median follow-up of 10.7-years. Overall LCD and LFD scores were not associated with higher multimorbidity risk. There was a higher multimorbidity risk for individuals in the highest quintile (Q5) of unhealthy LCD vs. lowest quintile (Q1) [fully adjusted hazard ratio (HR): 1.07, 95%CI: 1.01, 1.15, p-trend=.16] overall as well as among non-tobacco smokers [1.11 (1.00, 1.23, p-trend=.09]. The unhealthy LFD score was associated with multimorbidity overall [1.07 (1.00, 1.14), p-trend=.07] and never-smokers [1.12 (1.01, 1.24); p-trend=.01]. Healthy scores results were less consistent. The plant protein component had an inverse association with incident multimorbidity risk, whereas the low-quality-fat and animal protein components were each associated with higher risk of multimorbidity.CONCLUSIONDiet scores defined only by the total amount of carbohydrates or fat were not associated with risk of multimorbidity. Unhealthy diet scores including low-quality macronutrients and animal protein were associated with increased risk of multimorbidity.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710894","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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