Melissa Li,Dylan P Thibault,Lindsey B De Lott,Christopher A Gravel,Ellen E Freeman,Ali G Hamedani
BACKGROUNDVisual impairment is a potential risk factor for depression and other outcomes in older adults. In population-based studies, vision can be measured using self-report or performance-based visual acuity, but epidemiologic associations often depend on which measure is used.METHODSIn this Research Practice article, we illustrate the use of propensity scores to harmonize analyses of self-reported and performance-based vision in older adults. Using 2021 data from the National Health and Aging Trends Study (NHATS; n = 2,447), we measured associations between self-reported visual difficulty, distance visual impairment (logMAR >0.3), and depression. To harmonize self-reported and performance-based measures of vision, we modeled distance visual impairment as a function of self-reported vision and covariates and calculated exposure misclassification overlap weights. External validation was conducted using the Canadian Longitudinal Study on Aging (CLSA) and the Longitudinal Aging Study in India (LASI).RESULTSSelf-reported visual difficulty was associated with depression (adjusted OR 2.32, 95% CI: 1.46-3.69), but distance visual impairment was not (OR 1.41, 95% CI: 0.99-2.01). After exposure misclassification overlap weighting, self-reported vision was no longer associated with depression, and results mirrored the association between distance visual impairment and depression (OR 1.49, 95% CI: 0.93-2.36). Similar findings were observed in CLSA and LASI.CONCLUSIONSAssociations between vision and depression in older adults differ according to how vision is measured. In studies that measure self-reported vision but not visual acuity, propensity score methods that leverage known relationships between the two can be used to approximate associations between reduced visual acuity and health outcomes.
{"title":"Harmonization of self-reported and performance-based measures of vision using inverse probability weighting: an example using vision and depression in NHATS, CLSA, and LASI.","authors":"Melissa Li,Dylan P Thibault,Lindsey B De Lott,Christopher A Gravel,Ellen E Freeman,Ali G Hamedani","doi":"10.1093/gerona/glag019","DOIUrl":"https://doi.org/10.1093/gerona/glag019","url":null,"abstract":"BACKGROUNDVisual impairment is a potential risk factor for depression and other outcomes in older adults. In population-based studies, vision can be measured using self-report or performance-based visual acuity, but epidemiologic associations often depend on which measure is used.METHODSIn this Research Practice article, we illustrate the use of propensity scores to harmonize analyses of self-reported and performance-based vision in older adults. Using 2021 data from the National Health and Aging Trends Study (NHATS; n = 2,447), we measured associations between self-reported visual difficulty, distance visual impairment (logMAR >0.3), and depression. To harmonize self-reported and performance-based measures of vision, we modeled distance visual impairment as a function of self-reported vision and covariates and calculated exposure misclassification overlap weights. External validation was conducted using the Canadian Longitudinal Study on Aging (CLSA) and the Longitudinal Aging Study in India (LASI).RESULTSSelf-reported visual difficulty was associated with depression (adjusted OR 2.32, 95% CI: 1.46-3.69), but distance visual impairment was not (OR 1.41, 95% CI: 0.99-2.01). After exposure misclassification overlap weighting, self-reported vision was no longer associated with depression, and results mirrored the association between distance visual impairment and depression (OR 1.49, 95% CI: 0.93-2.36). Similar findings were observed in CLSA and LASI.CONCLUSIONSAssociations between vision and depression in older adults differ according to how vision is measured. In studies that measure self-reported vision but not visual acuity, propensity score methods that leverage known relationships between the two can be used to approximate associations between reduced visual acuity and health outcomes.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073333","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}
Ethan D Borre, Julie N Deleger, Lauren K Dillard, Juliessa M Pavon, Sachin J Shah, Judy R Dubno, Sherri L Smith, Kenneth A Freedberg, Howard W Francis, Christine S Ritchie, Gillian D Sanders Schmidler, Emily P Hyle
Background One-third of persons age 60 y+ have hearing loss, and hearing loss is a leading preventable risk factor for dementia. We estimated the number of age-associated dementia cases attributable to hearing loss in 2022. Methods We used DeciBHAL, a validated microsimulationof hearing loss that includes age- and sex-specific annual probabilities of incident hearing loss (0·1-10·4%) and dementia (0·3-7·1%). Utility decrements are incorporated yearly, based on hearing loss (-0·13 to -0·31) and dementia severity (-0·04 to -0·42), to calculate quality-adjusted life-years (QALYs). We estimated dementia incidence for persons with and without hearing loss by removing the estimated proportion attributable to hearing loss (adjusted incidence risk ratio, 2·0 [range: 1·5-2·5]). We projected two cohorts: the general US population and a hypothetical US population without hearing loss (counterfactual). We applied model-projected dementia incidence and utility among both cohorts to the 74,190,000 US adults >60 y and without dementia in 2022. Results Model-projected incident cases of dementia are 412,000/year (males) and 523,000/year (females). In the simulation without hearing loss, dementia cases/year fall to 339,000 for males and 455,000 for females projecting that 141,000 new dementia cases in 2022 would be attributable to hearing loss. In probabilistic sensitivity analysis, 95% of simulations projected the proportion of dementia cases attributable to hearing loss were 11·5-23·6% for males and 6·7-18·7% for females. Hearing loss and associated dementia reduced life-time QALYs by 1.38 for females and 1.69 for males. Conclusion Model-projected estimates support that hearing loss prevention could substantially reduce new dementia cases and should be a priority.
{"title":"The Impact of Hearing Loss on Annual Incident Age-Associated Dementia Cases and Quality of Life in the US","authors":"Ethan D Borre, Julie N Deleger, Lauren K Dillard, Juliessa M Pavon, Sachin J Shah, Judy R Dubno, Sherri L Smith, Kenneth A Freedberg, Howard W Francis, Christine S Ritchie, Gillian D Sanders Schmidler, Emily P Hyle","doi":"10.1093/gerona/glaf295","DOIUrl":"https://doi.org/10.1093/gerona/glaf295","url":null,"abstract":"Background One-third of persons age 60 y+ have hearing loss, and hearing loss is a leading preventable risk factor for dementia. We estimated the number of age-associated dementia cases attributable to hearing loss in 2022. Methods We used DeciBHAL, a validated microsimulationof hearing loss that includes age- and sex-specific annual probabilities of incident hearing loss (0·1-10·4%) and dementia (0·3-7·1%). Utility decrements are incorporated yearly, based on hearing loss (-0·13 to -0·31) and dementia severity (-0·04 to -0·42), to calculate quality-adjusted life-years (QALYs). We estimated dementia incidence for persons with and without hearing loss by removing the estimated proportion attributable to hearing loss (adjusted incidence risk ratio, 2·0 [range: 1·5-2·5]). We projected two cohorts: the general US population and a hypothetical US population without hearing loss (counterfactual). We applied model-projected dementia incidence and utility among both cohorts to the 74,190,000 US adults >60 y and without dementia in 2022. Results Model-projected incident cases of dementia are 412,000/year (males) and 523,000/year (females). In the simulation without hearing loss, dementia cases/year fall to 339,000 for males and 455,000 for females projecting that 141,000 new dementia cases in 2022 would be attributable to hearing loss. In probabilistic sensitivity analysis, 95% of simulations projected the proportion of dementia cases attributable to hearing loss were 11·5-23·6% for males and 6·7-18·7% for females. Hearing loss and associated dementia reduced life-time QALYs by 1.38 for females and 1.69 for males. Conclusion Model-projected estimates support that hearing loss prevention could substantially reduce new dementia cases and should be a priority.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109955","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}
Oonjee Oh,Sean Harrison,Justine S Sefcik,Therese S Richmond,Nancy Hodgson,George Demiris
BACKGROUNDPassive monitoring can support aging in place for older adults with mild cognitive impairment (MCI). Yet, their trust in the technology is crucial as the devices are installed in their homes, collecting data throughout their daily activities. We aimed to understand the perceptions of older adults with MCI to having passive monitoring technology embedded in their residence and examine their trust within this context.METHODSFor this qualitative descriptive study, data were obtained from a 12-month study that used passive monitoring technology to predict fall risks among community-dwelling older adults with MCI. We analyzed 30 exit interviews via directed content analysis using trust-related constructs outlined by Lankton et al.RESULTSFindings are presented under the model's constructs. Under reliability and integrity, participants described their perception of the sensor's omnipresence, its impact on privacy, and interactions with the team that made them feel safe. Under helpfulness and benevolence, we identified participants' views on the device's benefits, as well as the importance of having someone who is responsive to their data. Under functionality and competency, participants reflected on the sensor's intended unobtrusiveness and its accuracy in capturing gait patterns, along with the necessary infrastructures and indicators for proper functioning.CONCLUSIONSParticipants conceptualized depth sensors as more than a device, instead associating it with human agents who monitored them and interpreted their data. Despite the passive nature of the technology, successful implementation of monitoring systems requires ongoing human involvement and communication with the participants in order to build trust within the community.
{"title":"\"I had eyes on me to help me\": a qualitative descriptive study on trust in passive monitoring systems among older adults with mild cognitive impairment.","authors":"Oonjee Oh,Sean Harrison,Justine S Sefcik,Therese S Richmond,Nancy Hodgson,George Demiris","doi":"10.1093/gerona/glag018","DOIUrl":"https://doi.org/10.1093/gerona/glag018","url":null,"abstract":"BACKGROUNDPassive monitoring can support aging in place for older adults with mild cognitive impairment (MCI). Yet, their trust in the technology is crucial as the devices are installed in their homes, collecting data throughout their daily activities. We aimed to understand the perceptions of older adults with MCI to having passive monitoring technology embedded in their residence and examine their trust within this context.METHODSFor this qualitative descriptive study, data were obtained from a 12-month study that used passive monitoring technology to predict fall risks among community-dwelling older adults with MCI. We analyzed 30 exit interviews via directed content analysis using trust-related constructs outlined by Lankton et al.RESULTSFindings are presented under the model's constructs. Under reliability and integrity, participants described their perception of the sensor's omnipresence, its impact on privacy, and interactions with the team that made them feel safe. Under helpfulness and benevolence, we identified participants' views on the device's benefits, as well as the importance of having someone who is responsive to their data. Under functionality and competency, participants reflected on the sensor's intended unobtrusiveness and its accuracy in capturing gait patterns, along with the necessary infrastructures and indicators for proper functioning.CONCLUSIONSParticipants conceptualized depth sensors as more than a device, instead associating it with human agents who monitored them and interpreted their data. Despite the passive nature of the technology, successful implementation of monitoring systems requires ongoing human involvement and communication with the participants in order to build trust within the community.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073334","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 Dong,Ping Ping,Si-Qi Wang,Yi Ma,Xiang-Feng Chen
The early-onset transcriptional phenotype of senescence has been revealed in spermatogenic dysfunctional testes of patients at childbearing age. However, limited studies have reported the biomarker and function of testicular senescence-associated genes (SAGs) in the spermatogenic dysfunction of young men. In this study, two single-cell RNA sequencing (scRNA-seq) datasets, three bulk microarray datasets, and testicular tissue from older mice, older male, patients at childbearing age with full spermatogenesis or spermatogenic dysfunction were employed to recognize the aging-related biomarker for early-onset alterations of testicular SAGs. We found RPS14, an upregulated testicular SAGs in testes of older men, was an important biomarker for early-onset alterations of testicular SAG in young spermatogenic dysfunctional testes. RPS14 was significantly upregulated in young patients' testes with spermatogenic dysfunction. Importantly, RPS14 showed significant correlation with Johnsen scores and follicle-stimulating hormone levels, and had potential predictive value in sperm retrieval surgery. Besides, RPS14 was found to be deeply involved in the testicular immune microenvironment and significantly correlated with testicular mast cells. The scRNA-seq analyses and immunofluorescence illustrated the partially similar expression pattern and distribution of RPS14 in testes of both older males and young males with spermatogenic dysfunction. Moreover, the ribosome pathway might be the core mechanism through which this gene regulates the function of testicular cells. RPS14 was shown to be an aging-related biomarker which might be involved in the pathogenesis of spermatogenic dysfunction of young patients. The findings might offer a potential diagnostic marker as well as a therapeutic target for young patients diagnosed with male infertility.
{"title":"RPS14 as an aging-related biomarker for early-onset alterations of testicular senescence-associated genes in spermatogenic dysfunction at childbearing age.","authors":"Fan Dong,Ping Ping,Si-Qi Wang,Yi Ma,Xiang-Feng Chen","doi":"10.1093/gerona/glag020","DOIUrl":"https://doi.org/10.1093/gerona/glag020","url":null,"abstract":"The early-onset transcriptional phenotype of senescence has been revealed in spermatogenic dysfunctional testes of patients at childbearing age. However, limited studies have reported the biomarker and function of testicular senescence-associated genes (SAGs) in the spermatogenic dysfunction of young men. In this study, two single-cell RNA sequencing (scRNA-seq) datasets, three bulk microarray datasets, and testicular tissue from older mice, older male, patients at childbearing age with full spermatogenesis or spermatogenic dysfunction were employed to recognize the aging-related biomarker for early-onset alterations of testicular SAGs. We found RPS14, an upregulated testicular SAGs in testes of older men, was an important biomarker for early-onset alterations of testicular SAG in young spermatogenic dysfunctional testes. RPS14 was significantly upregulated in young patients' testes with spermatogenic dysfunction. Importantly, RPS14 showed significant correlation with Johnsen scores and follicle-stimulating hormone levels, and had potential predictive value in sperm retrieval surgery. Besides, RPS14 was found to be deeply involved in the testicular immune microenvironment and significantly correlated with testicular mast cells. The scRNA-seq analyses and immunofluorescence illustrated the partially similar expression pattern and distribution of RPS14 in testes of both older males and young males with spermatogenic dysfunction. Moreover, the ribosome pathway might be the core mechanism through which this gene regulates the function of testicular cells. RPS14 was shown to be an aging-related biomarker which might be involved in the pathogenesis of spermatogenic dysfunction of young patients. The findings might offer a potential diagnostic marker as well as a therapeutic target for young patients diagnosed with male infertility.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"102 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056517","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}
Julianna Liu,Steven E Arnold,Pia Kivisäkk,Hadia Fatima,Eva M Schmitt,Edward R Marcantonio,Alvaro Pascual-Leone,Mouhsin M Shafi,Michele Cavallari,Richard N Jones,Long H Ngo,Sharon K Inouye,Sarinnapha M Vasunilashorn,Tamara G Fong
BACKGROUNDDelirium is a common complication of hospitalization with poor outcomes, but its underlying pathophysiology is poorly understood. We investigated the association of preoperative glial fibrillary acidic protein (GFAP), a biomarker of reactive astrocytosis, with delirium incidence and severity.METHODSData were obtained from the ongoing prospective Successful Aging after Elective Surgery (SAGES) study. GFAP was measured in preoperative plasma (n = 529). Post-operative delirium incidence and severity were measured using the Confusion Assessment Method (CAM) and CAM-S (0-19, 19 worst), respectively. A multivariable generalized linear model (GLM) with log link and binary or Poisson error distribution was used to estimate the relative risk of delirium by GFAP quartile scale, and GLM with identity link was used to examine the association of preoperative GFAP and delirium severity.RESULTSOverall mean preoperative GFAP value was 289.6 ± 153.3 pg/ml; mean value by quartile (Q) was 148.1 ± 28.6 pg/ml for Q1, 220.5 ± 19.8 pg/ml for Q2, 298.2 ± 28.4 pg/ml for Q3, and 503.4 ± 128.3 pg/ml for Q4. Delirium incidence by GFAP level was 16% in Q1, 24% in Q2, 25% in Q3, and 28% in Q4 (Cochran Trend test P-value = 0.031; adjusted P-value = 0.205). Higher GFAP levels (4th vs. 1st quartile) were associated with greater risk of incident delirium (adjusted relative risk 1.70, 95% confidence interval (CI): 1.01-2.86) and greater delirium severity (adjusted mean difference 0.86, 95% CI: 0.004-1.71).CONCLUSIONSHigh preoperative plasma GFAP was associated with increased delirium incidence and severity, suggesting GFAP may serve as a risk marker for delirium. Brain vulnerability in the setting of astrocytosis may contribute to delirium pathophysiology.
{"title":"Preoperative plasma glial fibrillary acidic protein and postoperative delirium in older adults.","authors":"Julianna Liu,Steven E Arnold,Pia Kivisäkk,Hadia Fatima,Eva M Schmitt,Edward R Marcantonio,Alvaro Pascual-Leone,Mouhsin M Shafi,Michele Cavallari,Richard N Jones,Long H Ngo,Sharon K Inouye,Sarinnapha M Vasunilashorn,Tamara G Fong","doi":"10.1093/gerona/glag017","DOIUrl":"https://doi.org/10.1093/gerona/glag017","url":null,"abstract":"BACKGROUNDDelirium is a common complication of hospitalization with poor outcomes, but its underlying pathophysiology is poorly understood. We investigated the association of preoperative glial fibrillary acidic protein (GFAP), a biomarker of reactive astrocytosis, with delirium incidence and severity.METHODSData were obtained from the ongoing prospective Successful Aging after Elective Surgery (SAGES) study. GFAP was measured in preoperative plasma (n = 529). Post-operative delirium incidence and severity were measured using the Confusion Assessment Method (CAM) and CAM-S (0-19, 19 worst), respectively. A multivariable generalized linear model (GLM) with log link and binary or Poisson error distribution was used to estimate the relative risk of delirium by GFAP quartile scale, and GLM with identity link was used to examine the association of preoperative GFAP and delirium severity.RESULTSOverall mean preoperative GFAP value was 289.6 ± 153.3 pg/ml; mean value by quartile (Q) was 148.1 ± 28.6 pg/ml for Q1, 220.5 ± 19.8 pg/ml for Q2, 298.2 ± 28.4 pg/ml for Q3, and 503.4 ± 128.3 pg/ml for Q4. Delirium incidence by GFAP level was 16% in Q1, 24% in Q2, 25% in Q3, and 28% in Q4 (Cochran Trend test P-value = 0.031; adjusted P-value = 0.205). Higher GFAP levels (4th vs. 1st quartile) were associated with greater risk of incident delirium (adjusted relative risk 1.70, 95% confidence interval (CI): 1.01-2.86) and greater delirium severity (adjusted mean difference 0.86, 95% CI: 0.004-1.71).CONCLUSIONSHigh preoperative plasma GFAP was associated with increased delirium incidence and severity, suggesting GFAP may serve as a risk marker for delirium. Brain vulnerability in the setting of astrocytosis may contribute to delirium pathophysiology.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"205 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044620","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}
Calcium chloride can be used as a food additive and in medicine. The intake of calcium chloride can elevate the intracellular Ca2+ level, which subsequently activates the downstream proteins in the Ca2+/calmodulin-dependent protein kinase (CaMK) family. Based on evidence from the literature, we hypothesized that the calcium chloride supplementation may promote longevity by increasing intracellular Ca2+ levels, thereby activating the UNC-43/DAF-16 pathway, with potential involvement of the CKK-1 and CMK-1. The lifespan assays, health indexes (pharyngeal pumping and body bends), calcium imaging to assess the Ca2+ level, loss-of-function assays for the mutants, DAF-16 nuclear localization, UNC-43 protein localization and C. elegans RNA interference (RNAi) experiments were conducted. The results showed that the supplementation of calcium chloride significantly extended the lifespan in a dose-dependent manner. At the most effective dose (2000 nmol/plate), calcium chloride increased the mean lifespan by 15.4%, enhanced the calcium-level fluorescence by 2.8 folds, and improved both the health indices. The longevity effects induced by the calcium chloride required the CKK-1, CMK-1, UNC-43 and DAF-16 proteins. Moreover, both the DAF-16 nuclear translocation and the longevity effects were significantly suppressed by the RNAi targeting the CKK-1, CMK-1 and UNC-43. Importantly, the maintenance of the UNC-43 in the cytoplasm was dependent on the CKK-1 and CMK-1, as demonstrated by the RNAi analyses. All of these results indicated that the calcium chloride supplementation can exert the longevity effects in the C. elegans via a CKK-1 and CMK-1-dependent UNC-43/DAF-16 signaling mechanism.
{"title":"Calcium chloride supplementation promotes longevity in Caenorhabditis elegans via a CKK-1 and CMK-1-dependent UNC-43/DAF-16 signaling mechanism.","authors":"Che-Hsu Chin,Nae-Cherng Yang","doi":"10.1093/gerona/glag016","DOIUrl":"https://doi.org/10.1093/gerona/glag016","url":null,"abstract":"Calcium chloride can be used as a food additive and in medicine. The intake of calcium chloride can elevate the intracellular Ca2+ level, which subsequently activates the downstream proteins in the Ca2+/calmodulin-dependent protein kinase (CaMK) family. Based on evidence from the literature, we hypothesized that the calcium chloride supplementation may promote longevity by increasing intracellular Ca2+ levels, thereby activating the UNC-43/DAF-16 pathway, with potential involvement of the CKK-1 and CMK-1. The lifespan assays, health indexes (pharyngeal pumping and body bends), calcium imaging to assess the Ca2+ level, loss-of-function assays for the mutants, DAF-16 nuclear localization, UNC-43 protein localization and C. elegans RNA interference (RNAi) experiments were conducted. The results showed that the supplementation of calcium chloride significantly extended the lifespan in a dose-dependent manner. At the most effective dose (2000 nmol/plate), calcium chloride increased the mean lifespan by 15.4%, enhanced the calcium-level fluorescence by 2.8 folds, and improved both the health indices. The longevity effects induced by the calcium chloride required the CKK-1, CMK-1, UNC-43 and DAF-16 proteins. Moreover, both the DAF-16 nuclear translocation and the longevity effects were significantly suppressed by the RNAi targeting the CKK-1, CMK-1 and UNC-43. Importantly, the maintenance of the UNC-43 in the cytoplasm was dependent on the CKK-1 and CMK-1, as demonstrated by the RNAi analyses. All of these results indicated that the calcium chloride supplementation can exert the longevity effects in the C. elegans via a CKK-1 and CMK-1-dependent UNC-43/DAF-16 signaling mechanism.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044617","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}
Sikandar H Khan,Sara C Lahue,Anthony J Perkins,Maya Haouili,Jordan Baechle,Matias Fuentealba,Samreen Jawaid,Loren Lavadia,Sophia Wang,Stephanie Roa Diaz,Thelma Y Garcia,David Furman,Sujuan Gao,Malaz A Boustani,Babar Khan,John C Newman
Epigenetic clocks (EC) measuring epigenetic age (EA) and epigenetic age acceleration (EAA) are biomarkers of biological aging, but their association with intensive care unit (ICU) delirium remains underexplored. This is a pilot study utilizing blood samples from participants enrolled in Pharmacological Management of Delirium (PMD). Serum samples were collected within 48 hours of ICU admission. DNA isolated from serum clots was analyzed in triplicate for DNA methylation (DNAm). EA and EAA were computed for the Horvath, Hannum, PhenoAge, Horvath Skin & Blood, Telomere Length (TL), Best Linear Unbiased Predictor (BLUP), Elastic Network (EN), GrimAge1, GrimAge2, and DunedinPACE ECs from DNAm data. Principal-component clocks were also assessed. Coma, delirium, and delirium severity were assessed twice daily. LOS was assessed using electronic medical records. Spearman correlations were computed for relationships between EA/EAA and delirium outcomes using SAS. A convenience sample of 20 ICU patients with delirium was included. Mean age was 66.7 years (SD = 11.3), 12% were female, and 50% were Black. The median delirium/coma-free days (DCFD) by day 8 were 3 (IQR 0, 6.5). The intra-class correlation coefficients for EA ranged from 0.893 to 0.999, indicating good reliability and minimal variability across the replicates. EN EAA was moderately inversely correlated with mean CAM-ICU-7 scores by day 8 (Spearman r= -0.54, p = 0.01) and discharge (r= -0.48, p = 0.03). No other correlations between other EA/EAAs and delirium, ICU or hospital LOS reached statistical significance. This pilot study demonstrates the feasibility of using ECs from serum clots. Larger studies are needed to assess the relationship between EA/EAA and delirium.
{"title":"Exploring the Association between Epigenetic Age and Intensive Care Unit Delirium: A Pilot Feasibility Study.","authors":"Sikandar H Khan,Sara C Lahue,Anthony J Perkins,Maya Haouili,Jordan Baechle,Matias Fuentealba,Samreen Jawaid,Loren Lavadia,Sophia Wang,Stephanie Roa Diaz,Thelma Y Garcia,David Furman,Sujuan Gao,Malaz A Boustani,Babar Khan,John C Newman","doi":"10.1093/gerona/glag015","DOIUrl":"https://doi.org/10.1093/gerona/glag015","url":null,"abstract":"Epigenetic clocks (EC) measuring epigenetic age (EA) and epigenetic age acceleration (EAA) are biomarkers of biological aging, but their association with intensive care unit (ICU) delirium remains underexplored. This is a pilot study utilizing blood samples from participants enrolled in Pharmacological Management of Delirium (PMD). Serum samples were collected within 48 hours of ICU admission. DNA isolated from serum clots was analyzed in triplicate for DNA methylation (DNAm). EA and EAA were computed for the Horvath, Hannum, PhenoAge, Horvath Skin & Blood, Telomere Length (TL), Best Linear Unbiased Predictor (BLUP), Elastic Network (EN), GrimAge1, GrimAge2, and DunedinPACE ECs from DNAm data. Principal-component clocks were also assessed. Coma, delirium, and delirium severity were assessed twice daily. LOS was assessed using electronic medical records. Spearman correlations were computed for relationships between EA/EAA and delirium outcomes using SAS. A convenience sample of 20 ICU patients with delirium was included. Mean age was 66.7 years (SD = 11.3), 12% were female, and 50% were Black. The median delirium/coma-free days (DCFD) by day 8 were 3 (IQR 0, 6.5). The intra-class correlation coefficients for EA ranged from 0.893 to 0.999, indicating good reliability and minimal variability across the replicates. EN EAA was moderately inversely correlated with mean CAM-ICU-7 scores by day 8 (Spearman r= -0.54, p = 0.01) and discharge (r= -0.48, p = 0.03). No other correlations between other EA/EAAs and delirium, ICU or hospital LOS reached statistical significance. This pilot study demonstrates the feasibility of using ECs from serum clots. Larger studies are needed to assess the relationship between EA/EAA and delirium.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044616","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}
BACKGROUNDGrowing evidence connects sleep disorders with cognitive impairment in older adults, though underlying biological mechanisms remain unclear. We investigated how plasma metabolic profiles mediate the relationship between sleep patterns and global cognition.METHODSIn a cross-sectional analysis of 3,888 participants aged ≥60 years from the West China Health and Aging Cohort, we analyzed associations between 221 metabolites with both sleep characteristics and cognitive outcomes (assessed via Mini-Mental State Examination), evaluated mediating roles of individual metabolites and composite metabolite scores, and assessed joint associations of genetic susceptibility, sleep patterns, and metabolic profiles with cognitive function. Analyses were adjusted for demographic, lifestyle, comorbidity, and medication factors.RESULTSWe identified 93 metabolites associated with sleep characteristics and 26 linked to cognitive outcomes. Four individual metabolites-ketoleucine, dodecanoic acid, ribonic acid, and ortho-hydroxyphenylacetic acid-mediated 1.67-3.25% of the sleep-cognition associations. Composite metabolite scores-both unrestricted and those restricted to branched-chain amino acid (BCAA) pathways-demonstrated stronger mediation effects, with proportions reaching up to 13.6%. Participants with concurrent exposure to poor sleep, high genetic risk, and adverse metabolic profiles showed significantly worse cognitive outcomes compared to those without these risk factors, with effect sizes exceeding those in single or dual exposure groups.CONCLUSIONSPlasma metabolic signatures, particularly those involving BCAA metabolism, may serve as biological intermediaries linking poor sleep to worse cognitive function in older adults and could help identify populations at an elevated risk of cognitive impairment. Longitudinal and experimental studies are required to validate these associations and develop metabolic-based strategies for cognitive preservation.
{"title":"Sleep, Metabolites, and Global Cognition: A Mediation Analysis of Plasma Metabolic Profiles in the West China Health and Aging Cohort.","authors":"Xueyao Wu,Qingwen Zhao,Xingyu Zhang,Haiyu Yan,Xinyang Dui,Ke Jiang,Xin Chen,Lei Lin,Tianpei Ma,Xunying Zhao,Jinyu Xiao,Tao Zhang,Lu Long,Jiaqiang Liao,Xia Jiang,Jiayuan Li","doi":"10.1093/gerona/glag012","DOIUrl":"https://doi.org/10.1093/gerona/glag012","url":null,"abstract":"BACKGROUNDGrowing evidence connects sleep disorders with cognitive impairment in older adults, though underlying biological mechanisms remain unclear. We investigated how plasma metabolic profiles mediate the relationship between sleep patterns and global cognition.METHODSIn a cross-sectional analysis of 3,888 participants aged ≥60 years from the West China Health and Aging Cohort, we analyzed associations between 221 metabolites with both sleep characteristics and cognitive outcomes (assessed via Mini-Mental State Examination), evaluated mediating roles of individual metabolites and composite metabolite scores, and assessed joint associations of genetic susceptibility, sleep patterns, and metabolic profiles with cognitive function. Analyses were adjusted for demographic, lifestyle, comorbidity, and medication factors.RESULTSWe identified 93 metabolites associated with sleep characteristics and 26 linked to cognitive outcomes. Four individual metabolites-ketoleucine, dodecanoic acid, ribonic acid, and ortho-hydroxyphenylacetic acid-mediated 1.67-3.25% of the sleep-cognition associations. Composite metabolite scores-both unrestricted and those restricted to branched-chain amino acid (BCAA) pathways-demonstrated stronger mediation effects, with proportions reaching up to 13.6%. Participants with concurrent exposure to poor sleep, high genetic risk, and adverse metabolic profiles showed significantly worse cognitive outcomes compared to those without these risk factors, with effect sizes exceeding those in single or dual exposure groups.CONCLUSIONSPlasma metabolic signatures, particularly those involving BCAA metabolism, may serve as biological intermediaries linking poor sleep to worse cognitive function in older adults and could help identify populations at an elevated risk of cognitive impairment. Longitudinal and experimental studies are required to validate these associations and develop metabolic-based strategies for cognitive preservation.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044618","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}
Atalie C Thompson,Lindsey I Abdelfattah,Emilie D Duchesneau,Amol Joshi,Amresh D Hanchate
BACKGROUNDFalls and fractures are a significant public health concern linked to visual impairment. Cataracts are the most common cause of visual impairment in older adults and can be corrected with cataract surgery. This study evaluated whether cataract surgery reduces the one-year risk of falls/fractures in Medicare beneficiaries with cataract.METHODSUsing 2019-2021 claims data from a nationally representative cohort of 940,233 Medicare fee-for-service enrollees (66+ years), we identified those with untreated cataract in 2019 and grouped them into those with and without cataract surgery in 2020. Using the surgery date (surgery group) or a randomly assigned date in 2020 (non-surgery group) as the index date, we identified incident falls/fractures (outpatient, emergency department, or inpatient) during the following 365 days. We used a propensity score-based (with average treatment effect on the treated weights) linear probability regression model to estimate the association of cataract surgery with the risk (likelihood) of falls/fractures, accounting for observed differences between those with and without surgery.RESULTSWithout surgery, the estimated likelihood of falls/fractures was 8.86% (95% CI: 8.53-9.18%). Cataract surgery was not associated with a significant difference in the risk of falls/fractures (risk difference= -0.15 percentage points; 95% CI: -1.0, 0.74). Similar findings were observed for subgroups by race and ethnicity, frailty, and fall/fracture history.CONCLUSIONSCataract surgery was not significantly associated with one-year risk of falls/fractures in Medicare beneficiaries. Future studies should evaluate fall risk over a longer follow-up period or the impact of surgery on self-reported falls not captured by the healthcare system.
{"title":"The association of cataract surgery with risk of falls and fractures among medicare enrollees with cataract.","authors":"Atalie C Thompson,Lindsey I Abdelfattah,Emilie D Duchesneau,Amol Joshi,Amresh D Hanchate","doi":"10.1093/gerona/glag002","DOIUrl":"https://doi.org/10.1093/gerona/glag002","url":null,"abstract":"BACKGROUNDFalls and fractures are a significant public health concern linked to visual impairment. Cataracts are the most common cause of visual impairment in older adults and can be corrected with cataract surgery. This study evaluated whether cataract surgery reduces the one-year risk of falls/fractures in Medicare beneficiaries with cataract.METHODSUsing 2019-2021 claims data from a nationally representative cohort of 940,233 Medicare fee-for-service enrollees (66+ years), we identified those with untreated cataract in 2019 and grouped them into those with and without cataract surgery in 2020. Using the surgery date (surgery group) or a randomly assigned date in 2020 (non-surgery group) as the index date, we identified incident falls/fractures (outpatient, emergency department, or inpatient) during the following 365 days. We used a propensity score-based (with average treatment effect on the treated weights) linear probability regression model to estimate the association of cataract surgery with the risk (likelihood) of falls/fractures, accounting for observed differences between those with and without surgery.RESULTSWithout surgery, the estimated likelihood of falls/fractures was 8.86% (95% CI: 8.53-9.18%). Cataract surgery was not associated with a significant difference in the risk of falls/fractures (risk difference= -0.15 percentage points; 95% CI: -1.0, 0.74). Similar findings were observed for subgroups by race and ethnicity, frailty, and fall/fracture history.CONCLUSIONSCataract surgery was not significantly associated with one-year risk of falls/fractures in Medicare beneficiaries. Future studies should evaluate fall risk over a longer follow-up period or the impact of surgery on self-reported falls not captured by the healthcare system.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005273","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}
BACKGROUNDLong-term exposure to air pollution has been linked to adverse health outcomes in older adults; however, its association with frailty, particularly the potential protective role of environmental factors such as greenness, remains insufficiently investigated.METHODSData from the Healthy Aging Longitudinal Study in Taiwan, which included 5336 community-dwelling individuals aged 55 years and older, were analyzed. Frailty was assessed using modified criteria from the Cardiovascular Health Study. Exposure to air pollutants was estimated using land use regression model with machine learning methods. Greenness was quantified using the normalized difference vegetation index (NDVI). Logistic regression models were used to examine associations between environmental exposures and frailty after adjustment for demographic, health, and lifestyle confounders.RESULTSExposure to PM2.5 and NO2 during the 1 to 9 years preceding the assessment was significantly associated with an increased risk of frailty and prefrailty. Conversely higher NDVI values exhibited a protective effect. Mutually adjusted models confirmed the robustness of the effects of PM2.5, indicating its influence persisted for up to 3 years. The aOR for PM2.5 was 1.103 per 10 µg/m³ increment for 3 year prior to the assessment, corresponding to an excess risk of 10.3% per 10 µg/m³ increase.CONCLUSIONSLong-term exposure to PM2.5 related to frailty in older adults, whereas greenness provides protective benefits. These findings indicate the importance of developing public health policies aimed at improving air quality and promoting greening in ensuring healthy aging.
{"title":"Ambient Air Pollution, Greenness and Frailty in an Elder Asian Population: A Multi-Center Study with Long-Term Exposure.","authors":"Ping Shih,Shu-Chun Chuang,Chao Agnes Hsiung,Chi-Hsien Chen,I-Chien Wu,Chu-Chih Chen,Shao-Yuan Chuang,Yuan-Ting Hsu,Chih-Da Wu,Shih-Chun Pan,Chih-Cheng Hsu,Yue Leon Guo","doi":"10.1093/gerona/glag003","DOIUrl":"https://doi.org/10.1093/gerona/glag003","url":null,"abstract":"BACKGROUNDLong-term exposure to air pollution has been linked to adverse health outcomes in older adults; however, its association with frailty, particularly the potential protective role of environmental factors such as greenness, remains insufficiently investigated.METHODSData from the Healthy Aging Longitudinal Study in Taiwan, which included 5336 community-dwelling individuals aged 55 years and older, were analyzed. Frailty was assessed using modified criteria from the Cardiovascular Health Study. Exposure to air pollutants was estimated using land use regression model with machine learning methods. Greenness was quantified using the normalized difference vegetation index (NDVI). Logistic regression models were used to examine associations between environmental exposures and frailty after adjustment for demographic, health, and lifestyle confounders.RESULTSExposure to PM2.5 and NO2 during the 1 to 9 years preceding the assessment was significantly associated with an increased risk of frailty and prefrailty. Conversely higher NDVI values exhibited a protective effect. Mutually adjusted models confirmed the robustness of the effects of PM2.5, indicating its influence persisted for up to 3 years. The aOR for PM2.5 was 1.103 per 10 µg/m³ increment for 3 year prior to the assessment, corresponding to an excess risk of 10.3% per 10 µg/m³ increase.CONCLUSIONSLong-term exposure to PM2.5 related to frailty in older adults, whereas greenness provides protective benefits. These findings indicate the importance of developing public health policies aimed at improving air quality and promoting greening in ensuring healthy aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"393 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005393","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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