Kyle J Bourassa,Kirsten H Dillon,Rachel L Rodriguez,Melanie E Garrett,Livia Anderson,Paul A Dennis,Terrie E Moffitt,Avshalom Caspi,Harvey Jay Cohen,Katherine S Hall,Gregory A Taylor,Jennifer C Naylor,Allison E Ashley-Koch,Jean C Beckham,Nathan A Kimbrel,
Injuries characterizing recent military service, such as traumatic brain injury and posttraumatic stress disorder, are linked to accelerated biological aging. If recent veterans have accelerated aging, they might also show early onset of aging-related phenotypes, such as frailty. In this study, we examined the prevalence of frailty and associations with biological aging using data from 1,654 post-9/11 veterans, who were followed for an average of 12.6 years. Biological aging was assessed using DunedinPACE and frailty was assessed using 11 years of Jen Frailty Index scores from electronic health records. We found a high proportion of frailty-25.5% of the post-9/11 veterans met criteria for frailty during the study. This is roughly double the prevalence among community-dwelling older adults, despite the cohort's average age of 50.2 years at study end. Veterans with faster aging had higher initial frailty scores (β, 0.21; 95% CI, 0.15-0.27), higher peak frailty scores (β, 0.24; 95% CI, 0.18-0.30), and larger increases in frailty scores over time (β, 0.15; 95% CI, 0.09-0.21, all ps < .001). Faster aging was associated with a 62% (95% CI, 44%-82%) greater rate of incident frailty over the follow up while accounting for demographics, baseline health, and smoking. These results suggest post-9/11 veterans are at risk of early onset frailty and this increased risk could be explained by accelerated rates of biological aging. Future research should replicate these results in nationally representative samples of post-9/11 veterans and explore whether screening for frailty should be implemented at younger ages for veterans.
{"title":"Accelerated Biological Aging and Midlife Frailty among U.S. Military Veterans.","authors":"Kyle J Bourassa,Kirsten H Dillon,Rachel L Rodriguez,Melanie E Garrett,Livia Anderson,Paul A Dennis,Terrie E Moffitt,Avshalom Caspi,Harvey Jay Cohen,Katherine S Hall,Gregory A Taylor,Jennifer C Naylor,Allison E Ashley-Koch,Jean C Beckham,Nathan A Kimbrel, ","doi":"10.1093/gerona/glaf255","DOIUrl":"https://doi.org/10.1093/gerona/glaf255","url":null,"abstract":"Injuries characterizing recent military service, such as traumatic brain injury and posttraumatic stress disorder, are linked to accelerated biological aging. If recent veterans have accelerated aging, they might also show early onset of aging-related phenotypes, such as frailty. In this study, we examined the prevalence of frailty and associations with biological aging using data from 1,654 post-9/11 veterans, who were followed for an average of 12.6 years. Biological aging was assessed using DunedinPACE and frailty was assessed using 11 years of Jen Frailty Index scores from electronic health records. We found a high proportion of frailty-25.5% of the post-9/11 veterans met criteria for frailty during the study. This is roughly double the prevalence among community-dwelling older adults, despite the cohort's average age of 50.2 years at study end. Veterans with faster aging had higher initial frailty scores (β, 0.21; 95% CI, 0.15-0.27), higher peak frailty scores (β, 0.24; 95% CI, 0.18-0.30), and larger increases in frailty scores over time (β, 0.15; 95% CI, 0.09-0.21, all ps < .001). Faster aging was associated with a 62% (95% CI, 44%-82%) greater rate of incident frailty over the follow up while accounting for demographics, baseline health, and smoking. These results suggest post-9/11 veterans are at risk of early onset frailty and this increased risk could be explained by accelerated rates of biological aging. Future research should replicate these results in nationally representative samples of post-9/11 veterans and explore whether screening for frailty should be implemented at younger ages for veterans.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477695","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}
Nahed El Kassar,Amy E DeZern,Janis Abkowitz,Andrew Artz,Isabel Beerman,Kelly Bolton,Maria M Brooks,Uma Borate,William B Ershler,Tomas Ganz,Theodosia A Kalfa,Alice Kuaban,Sean Leng,Daisuke Nakada,Aziz Nazha,Claudia Grossmann,Michael Pfeilstöcker,Chengxuan Qiu,Jennifer St Sauver,Mikkael A Sekeres,Eleanor M Simonsick,Kenneth E White,Dachuan Zhang,Luigi Ferrucci,George A Kuchel
Approximately 17% of people aged 65 years and older are anemic, and 10% of death certificates report anemia as a secondary cause of death in the US. Nonetheless, anemia remains unexplained in 30-50% of older adults. This unexplained anemia of aging (UAA) is a diagnosis of exclusion. The mechanism, impact, and progression of UAA remain unknown. At older ages, anemia adds to pre-existing co-morbidities with significant adverse health consequences, representing a compelling unmet clinical concern. The National Institute on Aging held a workshop in 2024 to discuss current knowledge and research opportunities. Topics included the epidemiology of anemia at older age, its clinical implications; probable mechanism(s) underlying UAA, ie; low grade inflammation's effects on erythropoiesis; the role of microbiota in iron regulation in bone marrow; the importance of ruling out a diagnosis of leukemic clonal hematopoiesis (CH), which is more prevalent in older age; the role of senescence and aging governing hematopoiesis, and effects of sex hormones on hematopoietic stem cell aging. Understanding the roles of these factors could reduce the proportion of the older anemic population whose anemia remains unexplained and offer insights into new potential diagnostic and intervention strategies. Speakers reviewed previous clinical trials in patients with UAA and CH. They discussed lessons learned, and future research priorities ., including efforts to develop new diagnostic algorithms and potential uses of machine learning.
{"title":"A Proposed Path to Explaining the Unexplained Anemia of Aging.","authors":"Nahed El Kassar,Amy E DeZern,Janis Abkowitz,Andrew Artz,Isabel Beerman,Kelly Bolton,Maria M Brooks,Uma Borate,William B Ershler,Tomas Ganz,Theodosia A Kalfa,Alice Kuaban,Sean Leng,Daisuke Nakada,Aziz Nazha,Claudia Grossmann,Michael Pfeilstöcker,Chengxuan Qiu,Jennifer St Sauver,Mikkael A Sekeres,Eleanor M Simonsick,Kenneth E White,Dachuan Zhang,Luigi Ferrucci,George A Kuchel","doi":"10.1093/gerona/glaf251","DOIUrl":"https://doi.org/10.1093/gerona/glaf251","url":null,"abstract":"Approximately 17% of people aged 65 years and older are anemic, and 10% of death certificates report anemia as a secondary cause of death in the US. Nonetheless, anemia remains unexplained in 30-50% of older adults. This unexplained anemia of aging (UAA) is a diagnosis of exclusion. The mechanism, impact, and progression of UAA remain unknown. At older ages, anemia adds to pre-existing co-morbidities with significant adverse health consequences, representing a compelling unmet clinical concern. The National Institute on Aging held a workshop in 2024 to discuss current knowledge and research opportunities. Topics included the epidemiology of anemia at older age, its clinical implications; probable mechanism(s) underlying UAA, ie; low grade inflammation's effects on erythropoiesis; the role of microbiota in iron regulation in bone marrow; the importance of ruling out a diagnosis of leukemic clonal hematopoiesis (CH), which is more prevalent in older age; the role of senescence and aging governing hematopoiesis, and effects of sex hormones on hematopoietic stem cell aging. Understanding the roles of these factors could reduce the proportion of the older anemic population whose anemia remains unexplained and offer insights into new potential diagnostic and intervention strategies. Speakers reviewed previous clinical trials in patients with UAA and CH. They discussed lessons learned, and future research priorities ., including efforts to develop new diagnostic algorithms and potential uses of machine learning.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477694","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}
BACKGROUNDThe effect of dietary micronutrient adequacy on hearing loss is unknown. The aim of this study was to examine the cross-sectional association between dietary micronutrient adequacy and hearing loss among community-dwelling older adults.METHODSThis study included 1608 adults aged 65 y from the Seniors-ENRICA-2 cohort. Habitual diet was assessed with a validated computerized diet history. The intakes of 10 micronutrients (calcium, magnesium, potassium, zinc, iodine, vitamins A, C, D, E, and folate) were expressed as percentages relative to dietary reference intakes, with higher scores indicating greater adequacy. Dietary micronutrient adequacy was computed as the average of all nutrient scores. Hearing loss was defined as pure-tone average >40 dB-aHL in the better ear for standard frequency (0.5, 1, and 2 kHz), speech frequency (0.5, 1, 2, and 4 kHz), and high frequency pure tone average (PTA) (3, 4, and 8 kHz). Logistic regression models were conducted, after adjusting for sociodemographic factors, lifestyle, comorbidities, cognitive impairment and hearing-related variables.RESULTSOf the 1608 participants, 813 were men (50.6%); mean (SD) age was 73.8 (4.3) years. The prevalence of hearing loss was 13.3% at speech frequency. A high dietary micronutrient adequacy index was associated with hearing loss: OR (95% CI) for tertile 3 vs. 1 was 0.57 (0.35-0.94) for standard frequency, 0.58 (0.38-0.89) for speech frequency, and 0.69 (0.51-0.93) for high frequency PTA. No differences were observed for the association among the subgroups of participants defined by sex, body mass index, physical activity and chronic diseases.CONCLUSIONHigher dietary-based micronutrient adequacy was associated with lower prevalence of hearing loss across all frequency ranges.
{"title":"Association between a dietary-based micronutrient adequacy index and hearing loss in community-dwelling older adults.","authors":"Humberto Yévenes-Briones,Erika Tapia-Portilla,Veronica Vega-Cabello,Jorge Rey-Martinez,Alberto Lana,Francisco Félix Caballero,Esther Lopez-Garcia","doi":"10.1093/gerona/glaf252","DOIUrl":"https://doi.org/10.1093/gerona/glaf252","url":null,"abstract":"BACKGROUNDThe effect of dietary micronutrient adequacy on hearing loss is unknown. The aim of this study was to examine the cross-sectional association between dietary micronutrient adequacy and hearing loss among community-dwelling older adults.METHODSThis study included 1608 adults aged 65 y from the Seniors-ENRICA-2 cohort. Habitual diet was assessed with a validated computerized diet history. The intakes of 10 micronutrients (calcium, magnesium, potassium, zinc, iodine, vitamins A, C, D, E, and folate) were expressed as percentages relative to dietary reference intakes, with higher scores indicating greater adequacy. Dietary micronutrient adequacy was computed as the average of all nutrient scores. Hearing loss was defined as pure-tone average >40 dB-aHL in the better ear for standard frequency (0.5, 1, and 2 kHz), speech frequency (0.5, 1, 2, and 4 kHz), and high frequency pure tone average (PTA) (3, 4, and 8 kHz). Logistic regression models were conducted, after adjusting for sociodemographic factors, lifestyle, comorbidities, cognitive impairment and hearing-related variables.RESULTSOf the 1608 participants, 813 were men (50.6%); mean (SD) age was 73.8 (4.3) years. The prevalence of hearing loss was 13.3% at speech frequency. A high dietary micronutrient adequacy index was associated with hearing loss: OR (95% CI) for tertile 3 vs. 1 was 0.57 (0.35-0.94) for standard frequency, 0.58 (0.38-0.89) for speech frequency, and 0.69 (0.51-0.93) for high frequency PTA. No differences were observed for the association among the subgroups of participants defined by sex, body mass index, physical activity and chronic diseases.CONCLUSIONHigher dietary-based micronutrient adequacy was associated with lower prevalence of hearing loss across all frequency ranges.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477699","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}
Malcolm P Forbes, Mark W Cox, Katharine Brewster, Mojtaba Lotfaliany, Mohammadreza Mohebbi, Gary Rance, Robyn L Woods, Carlene Britt, John J Mcneil, Michael Berk
Background Hearing loss (HL) is common in older adults and is associated with several adverse health outcomes. Although previous research has demonstrated a link between hearing impairment and depression, most studies have been cross-sectional or relied on a single baseline measure of hearing. Aims To investigate the association between longitudinal, time-varying audiometric measures of hearing and incident depression in older adults. A secondary aim was to assess whether hearing aid use modifies this association over time in those with moderate to severe HL. Methods We included 1,260 participants who underwent pure-tone audiometry at baseline, 18 months, and 36 months. Depression was defined using the CES-D-10 scale, with a cut-score of ≥ 8. Cox proportional hazards analyses were used to examine the link between hearing status (normal, mild HL, moderate/severe HL) and depression, adjusted for demographic, lifestyle, and clinical variables. Results Over a median follow-up of 7.3 years, participants with moderate to severe HL had a higher risk of incident depression (adjusted HR [aHR] 1.24; 95% CI 1.08–1.43, p < 0.01) compared with participants with normal hearing. Hearing aid use (≥ 6 hours self-reported use per day on average) in those with moderate to severe HL was associated with significantly reduced risk of incident depression (aHR 0.65; 95% CI 0.49–0.87, p < 0.01). Conclusion Moderate to severe HL is a significant risk factor for incident depression among older adults. Hearing aid use attenuated this risk. Future research should investigate mechanistic pathways linking HL and mood disturbances.
背景：听力损失（HL）在老年人中很常见，并与几种不良健康结果相关。虽然以前的研究已经证明听力障碍和抑郁症之间存在联系，但大多数研究都是横向的，或者依赖于单一的听力基线测量。目的探讨老年人纵向时变听力测量与抑郁症的关系。第二个目的是评估在中度至重度HL患者中，助听器的使用是否会随着时间的推移改变这种关联。方法我们纳入了1260名参与者，他们在基线、18个月和36个月时接受了纯音听力测量。采用CES-D-10量表定义抑郁，cut-score≥8。Cox比例风险分析用于检查听力状况（正常、轻度HL、中度/重度HL）与抑郁症之间的联系，并根据人口统计学、生活方式和临床变量进行调整。结果在中位随访7.3年期间，与听力正常的参与者相比，中度至重度HL患者发生抑郁症的风险更高（调整后HR [aHR] 1.24; 95% CI 1.08-1.43, p < 0.01）。中度至重度HL患者使用助听器（平均每天自述使用≥6小时）与抑郁症发生风险显著降低相关（aHR 0.65; 95% CI 0.49-0.87, p < 0.01）。结论中重度HL是老年人发生抑郁的重要危险因素。助听器的使用降低了这种风险。未来的研究应探讨HL与情绪障碍之间的机制途径。
{"title":"The Association Between Hearing Impairment and Incident Depression in Older Adults: A Longitudinal Analysis","authors":"Malcolm P Forbes, Mark W Cox, Katharine Brewster, Mojtaba Lotfaliany, Mohammadreza Mohebbi, Gary Rance, Robyn L Woods, Carlene Britt, John J Mcneil, Michael Berk","doi":"10.1093/gerona/glaf250","DOIUrl":"https://doi.org/10.1093/gerona/glaf250","url":null,"abstract":"Background Hearing loss (HL) is common in older adults and is associated with several adverse health outcomes. Although previous research has demonstrated a link between hearing impairment and depression, most studies have been cross-sectional or relied on a single baseline measure of hearing. Aims To investigate the association between longitudinal, time-varying audiometric measures of hearing and incident depression in older adults. A secondary aim was to assess whether hearing aid use modifies this association over time in those with moderate to severe HL. Methods We included 1,260 participants who underwent pure-tone audiometry at baseline, 18 months, and 36 months. Depression was defined using the CES-D-10 scale, with a cut-score of ≥ 8. Cox proportional hazards analyses were used to examine the link between hearing status (normal, mild HL, moderate/severe HL) and depression, adjusted for demographic, lifestyle, and clinical variables. Results Over a median follow-up of 7.3 years, participants with moderate to severe HL had a higher risk of incident depression (adjusted HR [aHR] 1.24; 95% CI 1.08–1.43, p &lt; 0.01) compared with participants with normal hearing. Hearing aid use (≥ 6 hours self-reported use per day on average) in those with moderate to severe HL was associated with significantly reduced risk of incident depression (aHR 0.65; 95% CI 0.49–0.87, p &lt; 0.01). Conclusion Moderate to severe HL is a significant risk factor for incident depression among older adults. Hearing aid use attenuated this risk. Future research should investigate mechanistic pathways linking HL and mood disturbances.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472708","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}
Jia Liu, Wei Xiang Gao, Wei Sen Zhang, Ya Li Jin, Lin Xu, Jiao Wang
Background China’s dramatic decline in fertility rates due to family planning policies and socioeconomic changes have significant impacts on women’s long-term health. We examined the associations of individual reproductive factors and reproductive risk scores (RRS) with all-cause, cardiovascular disease (CVD), and cancer mortality in Chinese women. Methods 19,833 women aged 50+ years from the Guangzhou Biobank Cohort Study were included. Reproductive factors include gravidity, parity, number of abortions, age at first pregnancy, duration of breastfeeding, age at menarche, age at menopause, and contraceptive use. Weighted and unweighted RRS was constructed by six reproductive characteristics associated with long-term mortality. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results During an average follow-up of 16.7 years, 4,310 deaths occurred. Per one-point increase in weighted RRS was associated with higher risks of all-cause (adjusted HR: 1.05, 95% CI: 1.03–1.07) and CVD mortality (1.07, 1.04–1.10), but not with cancer mortality (1.03, 0.99–1.07). Mortality was higher for 0 or ≥ 4 pregnancies than 3 pregnancies (1.32, 1.06–1.64 and 1.12, 1.02–1.22), 0 or ≥ 4 childbirths than 2 childbirths (1.46, 1.20–1.79 and 1.15, 1.05–1.25), ≥4 abortions than no abortions (1.10, 1.02–1.19), age at first pregnancy <22 years than 22–29 years (1.21, 1.13–1.30), and breastfeeding duration <3 months than the longer (1.23, 1.09–1.38). Age at menopause was negatively associated with all-cause mortality (0.99, 0.98–1.00 per one-year increase). Conclusion Reproductive factors, including gravidity, parity, abortion, age at first pregnancy, breastfeeding duration, and menopausal age, were significant determinants of mortality risk in older Chinese women.
{"title":"Reproductive Factors and Risk of Mortality in Older Women: A 16-year Follow-up of Guangzhou Biobank Cohort Study","authors":"Jia Liu, Wei Xiang Gao, Wei Sen Zhang, Ya Li Jin, Lin Xu, Jiao Wang","doi":"10.1093/gerona/glaf246","DOIUrl":"https://doi.org/10.1093/gerona/glaf246","url":null,"abstract":"Background China’s dramatic decline in fertility rates due to family planning policies and socioeconomic changes have significant impacts on women’s long-term health. We examined the associations of individual reproductive factors and reproductive risk scores (RRS) with all-cause, cardiovascular disease (CVD), and cancer mortality in Chinese women. Methods 19,833 women aged 50+ years from the Guangzhou Biobank Cohort Study were included. Reproductive factors include gravidity, parity, number of abortions, age at first pregnancy, duration of breastfeeding, age at menarche, age at menopause, and contraceptive use. Weighted and unweighted RRS was constructed by six reproductive characteristics associated with long-term mortality. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results During an average follow-up of 16.7 years, 4,310 deaths occurred. Per one-point increase in weighted RRS was associated with higher risks of all-cause (adjusted HR: 1.05, 95% CI: 1.03–1.07) and CVD mortality (1.07, 1.04–1.10), but not with cancer mortality (1.03, 0.99–1.07). Mortality was higher for 0 or ≥ 4 pregnancies than 3 pregnancies (1.32, 1.06–1.64 and 1.12, 1.02–1.22), 0 or ≥ 4 childbirths than 2 childbirths (1.46, 1.20–1.79 and 1.15, 1.05–1.25), ≥4 abortions than no abortions (1.10, 1.02–1.19), age at first pregnancy &lt;22 years than 22–29 years (1.21, 1.13–1.30), and breastfeeding duration &lt;3 months than the longer (1.23, 1.09–1.38). Age at menopause was negatively associated with all-cause mortality (0.99, 0.98–1.00 per one-year increase). Conclusion Reproductive factors, including gravidity, parity, abortion, age at first pregnancy, breastfeeding duration, and menopausal age, were significant determinants of mortality risk in older Chinese women.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472709","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}
Fan Chen, Yi Guan, Bang-Bon Koo, Tammy M Scott, Wenjun Li, Kelsey M Mangano, Mahdi Garelnabi, Rafeeque Bhadelia, Katherine L Tucker
Background Magnesium’s (Mg) role in brain aging is under-studied. We examined associations of dietary and serum Mg with MRI and cognitive measures in a cohort with >10 y follow-up. Methods Adults from the Boston Puerto Rican Health Study who underwent MRI (n = 218 with serum Mg, n = 198 with Mg intake) and cognitive testing (n = 1049 with serum Mg, n = 1363 with Mg intake) were included. Hypomagnesemia was defined as serum Mg < 0.75 mmol/L, and adequate Mg intake as ≥ the Estimated Average Requirement (males : 350 mg/d, females : 265 mg/d). Multivariable linear regression and linear mixed-effects models were used to estimate associations of Mg with brain age gap (z-score), volumes (% of total intracranial volume), and cognitive scores (z-score). Effect modification by diabetes, hypertension, dyslipidemia, calcium: Mg intake ratio, or ApoE4 was evaluated. Results In the full sample, hypomagnesemia was not associated with brain MRI measures, but with global cognitive function [β (95% CI) = -0.058 (-0.11, -0.0020)], in fully adjusted models. Adequate Mg intake was associated with volumes of total gray matter [β (95% CI) = 2.83 (0.56, 5.11)], white matter [β (95% CI) = 1.54 (0.22, 2.86)], and multiple subregions, but not cognition. In participants with diabetes, hypomagnesemia was associated with lower volumes of multiple brain regions, which were not observed in participants without diabetes (P interaction<0.05). Limited or no interaction was detected for other potential modifiers, despite some variation in association direction or magnitude across subgroups. Conclusions Diabetes modified Mg’s association with brain volumes. Mg merits more attention among people with diabetes for preventing neurodegeneration.
{"title":"Associations of Serum Magnesium and Magnesium Intake with Brain Morphology and Cognitive Function in Puerto Rican Adults","authors":"Fan Chen, Yi Guan, Bang-Bon Koo, Tammy M Scott, Wenjun Li, Kelsey M Mangano, Mahdi Garelnabi, Rafeeque Bhadelia, Katherine L Tucker","doi":"10.1093/gerona/glaf241","DOIUrl":"https://doi.org/10.1093/gerona/glaf241","url":null,"abstract":"Background Magnesium’s (Mg) role in brain aging is under-studied. We examined associations of dietary and serum Mg with MRI and cognitive measures in a cohort with &gt;10 y follow-up. Methods Adults from the Boston Puerto Rican Health Study who underwent MRI (n = 218 with serum Mg, n = 198 with Mg intake) and cognitive testing (n = 1049 with serum Mg, n = 1363 with Mg intake) were included. Hypomagnesemia was defined as serum Mg &lt; 0.75 mmol/L, and adequate Mg intake as ≥ the Estimated Average Requirement (males : 350 mg/d, females : 265 mg/d). Multivariable linear regression and linear mixed-effects models were used to estimate associations of Mg with brain age gap (z-score), volumes (% of total intracranial volume), and cognitive scores (z-score). Effect modification by diabetes, hypertension, dyslipidemia, calcium: Mg intake ratio, or ApoE4 was evaluated. Results In the full sample, hypomagnesemia was not associated with brain MRI measures, but with global cognitive function [β (95% CI) = -0.058 (-0.11, -0.0020)], in fully adjusted models. Adequate Mg intake was associated with volumes of total gray matter [β (95% CI) = 2.83 (0.56, 5.11)], white matter [β (95% CI) = 1.54 (0.22, 2.86)], and multiple subregions, but not cognition. In participants with diabetes, hypomagnesemia was associated with lower volumes of multiple brain regions, which were not observed in participants without diabetes (P interaction&lt;0.05). Limited or no interaction was detected for other potential modifiers, despite some variation in association direction or magnitude across subgroups. Conclusions Diabetes modified Mg’s association with brain volumes. Mg merits more attention among people with diabetes for preventing neurodegeneration.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"165 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447437","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}
Jingxin Zhou, Yingcheng He, Jiawei Wang, Jing Cao, Xiaoling Huang, Menglu Chen, Juan Ye
Background Malnutrition, characterized by degeneration of body composition due to reduced intake or inflammation, shares some common mechanisms with age-related macular degeneration (AMD), while their associations remain unexplored Methods This cohort study utilized data from the UK Biobank. Participants without pre-existing AMD and with complete malnutrition data were included. Cox regression was employed to evaluate the longitudinal association. An ElasticNet model was used to derive a metabolomic signature of malnutrition, which was subsequently assessed for association with AMD. Malnutrition and the metabolomic signature were further tested for associations with photoreceptor thinning. Structural equation modeling (SEM) was applied to delineate underlying mechanisms. Results A total of 444,681 participants (mean age: 56.4 ± 8.1 years; 45.8% male) were included, with 32,086 (7.2%) diagnosed with malnutrition at baseline. Over a median follow-up of 13.6 years, 10,009 AMD cases were identified. Malnutrition was associated with an increased risk of AMD (HR 1.221, 95% CI 1.144–1.304, P < 0.001). Metabolomic signature of malnutrition derived from 127 metabolites was significantly associated with AMD risk (per SD increase: HR 1.073, 95% CI 1.037–1.110, P < 0.001), and thinner photoreceptor layer (β = -0.214, 95% CI -0.314 to -0.114, P < 0.001). SEM revealed that malnutrition increased AMD risk partially through metabolomic changes induced photoreceptor thinning. Conclusions Malnutrition in middle-aged adults was significantly associated with increased risk of AMD, which was mediated by metabolomic alterations that impaired photoreceptor health.
营养不良的特征是由于摄入减少或炎症引起的身体成分的退化，营养不良与年龄相关性黄斑变性（AMD）有一些共同的机制，但它们之间的关联尚不清楚。没有先前存在的AMD和有完整营养不良数据的参与者被纳入研究。采用Cox回归分析纵向相关性。使用ElasticNet模型得出营养不良的代谢组学特征，随后评估其与AMD的关联。营养不良和代谢组学特征进一步测试与光感受器变薄的关系。结构方程模型（SEM）被用于描述潜在的机制。结果共纳入444,681名参与者（平均年龄：56.4±8.1岁，45.8%为男性），其中32,086名（7.2%）在基线时被诊断为营养不良。在中位13.6年的随访中，发现了10,009例AMD病例。营养不良与AMD风险增加相关（HR 1.221, 95% CI 1.144-1.304, P < 0.001）。来自127种代谢物的营养不良代谢组学特征与AMD风险（每SD增加：HR 1.073, 95% CI 1.037-1.110, P < 0.001）和更薄的光感受器层（β = -0.214, 95% CI -0.314至-0.114,P < 0.001）显著相关。扫描电镜显示，营养不良增加AMD的风险部分是通过代谢组学变化引起的光感受器变薄。结论中年人营养不良与黄斑变性风险增加显著相关，黄斑变性与代谢组学改变介导的光感受器健康受损有关。
{"title":"Malnutrition and Age-Related Macular Degeneration: Mechanistic Insights from UK Biobank Metabolomic and Imaging Data","authors":"Jingxin Zhou, Yingcheng He, Jiawei Wang, Jing Cao, Xiaoling Huang, Menglu Chen, Juan Ye","doi":"10.1093/gerona/glaf229","DOIUrl":"https://doi.org/10.1093/gerona/glaf229","url":null,"abstract":"Background Malnutrition, characterized by degeneration of body composition due to reduced intake or inflammation, shares some common mechanisms with age-related macular degeneration (AMD), while their associations remain unexplored Methods This cohort study utilized data from the UK Biobank. Participants without pre-existing AMD and with complete malnutrition data were included. Cox regression was employed to evaluate the longitudinal association. An ElasticNet model was used to derive a metabolomic signature of malnutrition, which was subsequently assessed for association with AMD. Malnutrition and the metabolomic signature were further tested for associations with photoreceptor thinning. Structural equation modeling (SEM) was applied to delineate underlying mechanisms. Results A total of 444,681 participants (mean age: 56.4 ± 8.1 years; 45.8% male) were included, with 32,086 (7.2%) diagnosed with malnutrition at baseline. Over a median follow-up of 13.6 years, 10,009 AMD cases were identified. Malnutrition was associated with an increased risk of AMD (HR 1.221, 95% CI 1.144–1.304, P &lt; 0.001). Metabolomic signature of malnutrition derived from 127 metabolites was significantly associated with AMD risk (per SD increase: HR 1.073, 95% CI 1.037–1.110, P &lt; 0.001), and thinner photoreceptor layer (β = -0.214, 95% CI -0.314 to -0.114, P &lt; 0.001). SEM revealed that malnutrition increased AMD risk partially through metabolomic changes induced photoreceptor thinning. Conclusions Malnutrition in middle-aged adults was significantly associated with increased risk of AMD, which was mediated by metabolomic alterations that impaired photoreceptor health.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"153 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447438","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}
Sodiq Fakorede,Kai Cheng,Olubodun M Lateef,Okikiola Samuel Fakorede,Deqiang Wang,Dan Wang,Xia Liu
BACKGROUNDFalls are a leading cause of morbidity in older adults, with emerging evidence suggesting that systemic inflammation may contribute to this risk. C-reactive protein (CRP), a biomarker of inflammation, has been linked to various health issues, including declines in physical function. However, its direct influence on balance and fall risk remains uncertain. This study investigates the association between CRP levels and balance using observational data and Mendelian Randomization (MR) to explore its causal role in fall risk.METHODSWe analyzed data from the 2021-2023 National Health and Nutrition Examination Survey (NHANES), including 1,215 participants aged 60 and older. CRP levels were measured using immunoturbidimetric assays, and balance was assessed via the Modified Romberg Test. We used multivariable ordinal logistic regression models to evaluate the relationship between CRP and balance, adjusting for demographic, health, and lifestyle factors. Genetic instruments for CRP were derived from genome-wide association studies (GWAS), and MR analysis was performed using fall risk summary statistics (2,215 cases, 6,289 controls).RESULTSIn the NHANES cohort, higher CRP levels were associated with poorer balance (β = -0.201, p = 0.007). This association was stronger in males but not in females. MR analysis confirmed a causal link between elevated CRP and increased fall risk (OR = 1.13, p = 8.96 × 10-8), with no evidence of pleiotropy or heterogeneity.CONCLUSIONSour findings highlight CRP as a key factor influencing balance and a causal contributor to fall risk in older adults, suggesting that anti-inflammatory interventions may help reduce fall risk.
背景：跌倒是老年人发病的主要原因，越来越多的证据表明，全身性炎症可能导致这种风险。c反应蛋白（CRP）是炎症的一种生物标志物，与各种健康问题有关，包括身体机能下降。然而，它对平衡和跌倒风险的直接影响仍不确定。本研究利用观察数据和孟德尔随机化（MR）研究CRP水平与平衡之间的关系，以探讨其在跌倒风险中的因果作用。方法我们分析了2021-2023年全国健康与营养调查（NHANES）的数据，包括1215名60岁及以上的参与者。采用免疫比浊法测定CRP水平，并通过改良Romberg试验评估平衡。我们使用多变量有序逻辑回归模型来评估CRP与平衡之间的关系，调整了人口统计学、健康和生活方式因素。CRP的遗传仪器来源于全基因组关联研究（GWAS）， MR分析采用跌倒风险汇总统计（2215例，6289例对照）。结果在NHANES队列中，较高的CRP水平与较差的平衡相关（β = -0.201, p = 0.007）。这种关联在男性中更强，而在女性中则不然。MR分析证实CRP升高与跌倒风险增加之间存在因果关系（OR = 1.13, p = 8.96 × 10-8），未发现多效性或异质性的证据。结论：研究结果表明，CRP是影响平衡的关键因素，是老年人跌倒风险的因果因素，提示抗炎干预可能有助于降低跌倒风险。
{"title":"Association of Systemic Inflammation with Balance and Falls in Older Adults: NHANES and Mendelian Randomization Study.","authors":"Sodiq Fakorede,Kai Cheng,Olubodun M Lateef,Okikiola Samuel Fakorede,Deqiang Wang,Dan Wang,Xia Liu","doi":"10.1093/gerona/glaf242","DOIUrl":"https://doi.org/10.1093/gerona/glaf242","url":null,"abstract":"BACKGROUNDFalls are a leading cause of morbidity in older adults, with emerging evidence suggesting that systemic inflammation may contribute to this risk. C-reactive protein (CRP), a biomarker of inflammation, has been linked to various health issues, including declines in physical function. However, its direct influence on balance and fall risk remains uncertain. This study investigates the association between CRP levels and balance using observational data and Mendelian Randomization (MR) to explore its causal role in fall risk.METHODSWe analyzed data from the 2021-2023 National Health and Nutrition Examination Survey (NHANES), including 1,215 participants aged 60 and older. CRP levels were measured using immunoturbidimetric assays, and balance was assessed via the Modified Romberg Test. We used multivariable ordinal logistic regression models to evaluate the relationship between CRP and balance, adjusting for demographic, health, and lifestyle factors. Genetic instruments for CRP were derived from genome-wide association studies (GWAS), and MR analysis was performed using fall risk summary statistics (2,215 cases, 6,289 controls).RESULTSIn the NHANES cohort, higher CRP levels were associated with poorer balance (β = -0.201, p = 0.007). This association was stronger in males but not in females. MR analysis confirmed a causal link between elevated CRP and increased fall risk (OR = 1.13, p = 8.96 × 10-8), with no evidence of pleiotropy or heterogeneity.CONCLUSIONSour findings highlight CRP as a key factor influencing balance and a causal contributor to fall risk in older adults, suggesting that anti-inflammatory interventions may help reduce fall risk.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background To investigate the association of estimated glucose disposal rate (eGDR), a validated measure of insulin resistance (IR), with brain aging and dementia among diabetes-free people. Methods This study included 258,732 diabetes- and dementia-free adults aged ≥55 from UK Biobank, including 15,389 participants who underwent brain MRI scans. eGDR was assessed by a well-established formula. Brain age gap (BAG) was calculated as difference between machine learning-predicted brain age and chronological age. Dementia was ascertained based on medical records. Data were analyzed using Cox, Laplace, and linear regression. Results Over the follow-up, 7,063 participants developed dementia. The hazard ratios of dementia for eGDR quartiles 2-4 compared to eGDR quartile 1 were 0.88 (0.81, 0.96), 0.83 (0.76, 0.92), and 0.73 (0.66, 0.82), respectively. High eGDR was further associated with 1.31 (0.81, 1.80) years later onset of dementia. Those with high eGDR had 2.09 (1.74, 2.45) years younger brain age than chronological age. Among APOE ɛ4 carriers, those with high eGDR had 14% lower incidence of dementia and a 1.77-year gap between brain age and chronological age (P-for-interaction<0.001). Conclusion Higher eGDR is associated with prolonged onset of dementia and delayed brain aging among diabetes-free individuals, and could buffer genetic risk of APOE ɛ4.
{"title":"Estimated glucose disposal rate is associated with brain aging and dementia among diabetes-free older adults","authors":"Jiao Wang, Shuqi Wang, Abigail Dove, Sakura Sakakibara, Stéphanie Paillard-Borg, Marc Guitart-Masip, Jirong Yue, Weili Xu","doi":"10.1093/gerona/glaf243","DOIUrl":"https://doi.org/10.1093/gerona/glaf243","url":null,"abstract":"Background To investigate the association of estimated glucose disposal rate (eGDR), a validated measure of insulin resistance (IR), with brain aging and dementia among diabetes-free people. Methods This study included 258,732 diabetes- and dementia-free adults aged ≥55 from UK Biobank, including 15,389 participants who underwent brain MRI scans. eGDR was assessed by a well-established formula. Brain age gap (BAG) was calculated as difference between machine learning-predicted brain age and chronological age. Dementia was ascertained based on medical records. Data were analyzed using Cox, Laplace, and linear regression. Results Over the follow-up, 7,063 participants developed dementia. The hazard ratios of dementia for eGDR quartiles 2-4 compared to eGDR quartile 1 were 0.88 (0.81, 0.96), 0.83 (0.76, 0.92), and 0.73 (0.66, 0.82), respectively. High eGDR was further associated with 1.31 (0.81, 1.80) years later onset of dementia. Those with high eGDR had 2.09 (1.74, 2.45) years younger brain age than chronological age. Among APOE ɛ4 carriers, those with high eGDR had 14% lower incidence of dementia and a 1.77-year gap between brain age and chronological age (P-for-interaction&lt;0.001). Conclusion Higher eGDR is associated with prolonged onset of dementia and delayed brain aging among diabetes-free individuals, and could buffer genetic risk of APOE ɛ4.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"113 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427434","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}
BACKGROUNDBased on data from the Global Burden of Disease (GBD) 2021, this study assessed the burden of falls from 1990 to 2021, with a focus on older adults (≥60 years), regional disparities, and projections to 2040.METHODSAge-standardized rates (ASRs) of incidence, prevalence, mortality, DALYs, YLDs, and YLLs were analyzed, along with estimated annual percentage changes (EAPC) and decomposition analysis to quantify the effects of aging and population growth. Age-specific risk factors were estimated via Population Attributable Fraction, and health disparities were examined using the Slope Index of Inequality and Socio-demographic Index (SDI)-linked concentration index. A Bayesian Age-Period-Cohort model projected burdens to 2040.RESULTSAlthough the all-age incidence ASR of falls declined, it increased in older adults from 1990 to 2021 [2021 incidence ASR, 5218.93 (95% UI 4056.57-6569.67) per 100,000; EAPCs, 0.49 (95% CI 0.07-0.91)] and was projected to rise further by 2040. Population aging accounted 59.36% for the increase in fall-related death numbers from 1990 to 2021. Low bone mineral density was a leading risk factor for fall-related mortality and DALYs in older adults. The absolute numbers of all burden measures increased in older adults from 1990 to 2021, and were expected to worsen further by 2040. Health inequalities persisted in older adults: lower-SDI regions had higher mortality despite lower incidence/prevalence, while higher-SDI regions showed the opposite.CONCLUSIONSThe public health challenge posed by falls are substantial in older adults. Enhanced preventive strategies alongside efforts to address socioeconomic disparities are needed.
{"title":"Global Burden of Falls 1990-2021: Aging Effect, Age-Stratified Risk Factors, and Projection to 2040 in Older Adults.","authors":"Huimin Chen,Huijing Liu,Yunfei Long,Dongdong Wu,Wei Du,Jing He,Shuhua Li,Xinxin Ma,Haibo Chen,Wen Su","doi":"10.1093/gerona/glaf238","DOIUrl":"https://doi.org/10.1093/gerona/glaf238","url":null,"abstract":"BACKGROUNDBased on data from the Global Burden of Disease (GBD) 2021, this study assessed the burden of falls from 1990 to 2021, with a focus on older adults (≥60 years), regional disparities, and projections to 2040.METHODSAge-standardized rates (ASRs) of incidence, prevalence, mortality, DALYs, YLDs, and YLLs were analyzed, along with estimated annual percentage changes (EAPC) and decomposition analysis to quantify the effects of aging and population growth. Age-specific risk factors were estimated via Population Attributable Fraction, and health disparities were examined using the Slope Index of Inequality and Socio-demographic Index (SDI)-linked concentration index. A Bayesian Age-Period-Cohort model projected burdens to 2040.RESULTSAlthough the all-age incidence ASR of falls declined, it increased in older adults from 1990 to 2021 [2021 incidence ASR, 5218.93 (95% UI 4056.57-6569.67) per 100,000; EAPCs, 0.49 (95% CI 0.07-0.91)] and was projected to rise further by 2040. Population aging accounted 59.36% for the increase in fall-related death numbers from 1990 to 2021. Low bone mineral density was a leading risk factor for fall-related mortality and DALYs in older adults. The absolute numbers of all burden measures increased in older adults from 1990 to 2021, and were expected to worsen further by 2040. Health inequalities persisted in older adults: lower-SDI regions had higher mortality despite lower incidence/prevalence, while higher-SDI regions showed the opposite.CONCLUSIONSThe public health challenge posed by falls are substantial in older adults. Enhanced preventive strategies alongside efforts to address socioeconomic disparities are needed.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145374086","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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