The Journals Of Gerontology. Series A, Biological Sciences And Medical Sciences[JOURNAL]
Sun
200 papers
Uric acid to high-density lipoprotein cholesterol ratio as a novel biomarker for sarcopenia: a national study with machine learning insights.
Yang R, Cheng Z, Yang P … +3 more , Yang X, Liao W, Zhai S
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42172590 · Full text
BACKGROUND: Sarcopenia is a major age-related health burden. Although the uric acid to high-density lipoprotein cholesterol ratio (UHR) has been linked to sarcopenia, its underlying pathways and clinical utility remain u...
BACKGROUND: Sarcopenia is a major age-related health burden. Although the uric acid to high-density lipoprotein cholesterol ratio (UHR) has been linked to sarcopenia, its underlying pathways and clinical utility remain unclear. METHODS: We analyzed 9853 adults from the China Health and Retirement Longitudinal Study. Sarcopenia was defined by Asian Working Group for Sarcopenia 2019 Consensus criteria. We assessed the UHR-sarcopenia relationship using multivariable logistic regression and restricted cubic splines. Mediation analyses examined roles of insulin resistance (TyG index) and renal function (eGFR). Five machine learning algorithms were developed and evaluated in training (70%) and testing (30%) sets. Feature selection was performed using Boruta and LASSO, and model interpretability was assessed using SHapley Additive exPlanations (SHAP). RESULTS: Higher UHR was independently associated with lower odds of sarcopenia, with an adjusted odds ratio per-standard deviation increase of 0.75 (95% CI: 0.69-0.81; p < .001), and showed a nonlinear dose-response relationship. UHR correlated with better handgrip strength and chair-stand performance. The TyG index and eGFR mediated 16.44% and 2.03% of this association, respectively. In machine learning analyses, ROC-AUC values ranged from 0.73 to 0.77, with XGBoost showing the best performance. SHAP analysis based on the XGBoost model further identified UHR as the second most important predictor of sarcopenia, following age. CONCLUSIONS: Higher UHR was associated with lower sarcopenia risk in Chinese middle-aged and older adults, partly through metabolic and renal pathways. UHR may serve as a simple biomarker for sarcopenia risk stratification.
Establishing bone tissue level changes associated with cognitive impairment.
Ross RD, Dulion B, Wong J … +7 more , Gritsenko MA, Day LZ, McDermott JE, Jacobs JM, Leurgans SE, Yu L, Bennett DA
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42172587 · Publisher ↗
Alzheimer's disease (AD) and osteoporosis are common chronic conditions of aging. Although several studies have reported an association between the 2 conditions, there is limited information on tissue-level mechanisms. I...
Alzheimer's disease (AD) and osteoporosis are common chronic conditions of aging. Although several studies have reported an association between the 2 conditions, there is limited information on tissue-level mechanisms. In the current study, we performed unbiased proteomics on thoracic vertebral samples collected from female participants enrolled in the religious orders study (ROS) and Rush Memory and Aging Project (MAP) cohorts to assess bone tissue-level changes associated with AD and other dementia-associated neuropathologies. Cognitive functioning and other participant characteristics were collected as part of ROSMAP study visits. Post-mortem evaluations assessed the burden of β-amyloid and paired helical filament tau (PHFtau) tangles, and other common age-related neuropathologies. A total of 45 bone samples were utilized from 19 female participants with a clinical diagnosis of AD dementia and 26 without AD dementia. The association between bone tissue protein abundance and cognition measured proximate to death, as well as neuropathologic indices, were evaluated using linear regression or logistic regression models, as appropriate. Bone tissue abundance of minichromosomal maintenance protein 3 (MCM3) and ubiquitin carboxyl-terminal hydrolase 24 (USP24) were positively associated with cognition and negatively associated with PHFtau tangle density. MCMC3 was also associated with cerebral arteriosclerosis, while USP24 was associated with cerebral amyloid angiopathy. Our findings suggest that processes regulating bone cell division may be involved in the link between brain and bone aging in a relationship that may not be specific to AD.
Development and validation of an electronic health record-based frailty index in the UK Biobank.
Bowman GI, Seymour N, Reynolds C … +1 more , Evans LM
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42166742 · Publisher ↗
BACKGROUND: Frailty, an age-related loss of the ability to withstand stressors, is commonly measured using health deficit indices, often using survey or questionnaire data. We aimed to develop an electronic frailty index...
BACKGROUND: Frailty, an age-related loss of the ability to withstand stressors, is commonly measured using health deficit indices, often using survey or questionnaire data. We aimed to develop an electronic frailty index (eFI) using electronic health record (EHR) data linkages in the UK Biobank and assess its association with mortality. METHODS: We calculated an eFI using 43 deficits, each corresponding to phecodes mapped to the United Kingdom (UK) and international classification coding systems. We compared this eFI to a validated 49-item survey-based FI for the UK Biobank (UKB) and assessed associations of the eFI with risk of all-cause mortality (follow-up ≤ 10.2 years) and mortality following a stressor (heart attack or stroke) using Cox proportional hazard models. RESULTS: Mean eFI in this cohort (N = 208,982) was 0.058 (SD = 0.06) and was higher in females than males. A 10% higher baseline frailty was associated with higher risk of all-cause mortality (HR (95% CI)=2.00 (1.93-2.07)), although the magnitude of this association decreased when adjusting for socioeconomic-related covariates (HR (95% CI)=1.44 (1.38-1.51)). Associations were stronger in men than women. Electronic frailty index predicted mortality following both heart attack and stroke (HR (95% CI) = 1.59 (1.25-2.04) and HR = 1.33 (1.13-1.57), respectively). CONCLUSIONS: This EHR-based eFI has robust associations with mortality, suggesting that it can be used as a valid measure of frailty in the UKB and can potentially be applied to other datasets with EHR data.
Synergistic impact of rest-activity circadian rhythms and physical activity on all-cause and cardiovascular mortality.
Gu B, Zhang H, Yi M … +9 more , Si J, Xiao K, Sun L, Sun J, Zhao H, Zhao O, Ma Y, Luo H, Li J
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42166731 · Publisher ↗
BACKGROUND: This study investigated the independent and joint associations of rest-activity circadian rhythms (RACRs) and physical activity (PA) with all-cause and cardiovascular mortality, and explored the potential rol...
BACKGROUND: This study investigated the independent and joint associations of rest-activity circadian rhythms (RACRs) and physical activity (PA) with all-cause and cardiovascular mortality, and explored the potential role of accelerated biological aging. METHODS: We included 6621 adults from NHANES 2011-2014. RACR parameters were derived from wrist-worn ActiGraph GT3X+ data. Accelerated biological aging was assessed using Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel). Cox proportional hazards models were applied to investigate the associations of RACRs and PA with all-cause and cardiovascular mortality. Exploratory mediation analyses were used to explore the associations between accelerated biological aging, RACRs, and mortality risks. RESULTS: Over a median follow-up of 6.75 years, 518 all-cause deaths and 165 cardiovascular deaths were recorded. Compared with weak RACRs and inadequate PA, participants with strong RACRs and adequate PA had significantly lower risks of all-cause mortality (HR: 0.35, 95% CI: 0.24 to 0.51; p < .001) and cardiovascular mortality (HR: 0.25, 95% CI: 0.14 to 0.45; p < .001). In exploratory analyses, PhenoAgeAccel accounted for an estimated 13.55% (p < .001) and 21.67% (p = .002) of the associations between RACRs and all-cause and cardiovascular mortality, respectively, while BioAgeAccel accounted for an estimated 5.06% (p < .001) and 8.06% (p = .004). CONCLUSIONS: Disrupted RACRs are associated with higher mortality risks that could be attenuated by adequate physical activity. Exploratory analyses suggest that the associations between RACRs and mortality may be mediated in part by accelerated biological aging, but additional studies are needed to test this hypothesis.
Evaluating the predictive utility of European-based and transethnic polygenic risk scores for kidney function in older Black adults: insights from the Health and Retirement Study.
Cobb RJ, Thorpe RJ, Norris KC
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42166726 · Publisher ↗
BACKGROUND: Black populations in the U.S. experience a disproportionately faster progression of chronic kidney disease than the general population. Polygenic risk scores (PRS) are a promising tool for risk stratification...
BACKGROUND: Black populations in the U.S. experience a disproportionately faster progression of chronic kidney disease than the general population. Polygenic risk scores (PRS) are a promising tool for risk stratification, yet their utility in predicting kidney function across populations remains uncertain. METHODS: This study evaluates the effectiveness of European and trans-ethnic PRS in predicting kidney function among older Black adults from the 2010-2012 Health and Retirement Study (HRS) (N = 2080), a nationally representative sample of adults aged ≥50 years in the U.S. We assessed kidney function using an estimated glomerular filtration rate derived from cystatin C. The HRS constructed PRS from genome-wide association studies based on European and trans-ethnic ancestries. We used ordinary least-squares regression to examine the predictive power of European-based and transethnic PRS on kidney function, adjusting for demographic, behavioral, cardiometabolic risk, and socioeconomic factors. RESULTS: The mean kidney function is approximately 74 mL/min/1.73 m2, with a wide range, indicating significant heterogeneity among older Black adults. Findings suggest that neither the European nor the trans-ethnic PRS demonstrated a significant association with kidney function in demographic-adjusted models among older Black adults. Including behavioral, cardiometabolic, and socioeconomic factors did not change this relationship. CONCLUSIONS: Our findings underscore the challenges of applying PRS to predict kidney function among older Black adults. They also emphasize the need for more inclusive genomic research and the significant impact of clinical and sociodemographic factors on kidney function among older Black adults. These insights are vital for enhancing precision medicine and ensuring equitable genomic practices.
Examining the Relevance of Gait Speed Resiliencies to Different Stressors: the ARIC Study.
Windham BG, Sylvester HC, Henegan J … +7 more , McMullan M, Kucharska-Newton A, Palta P, Schrack JA, Mosley TH, Bandeen-Roche K, Griswold ME
J Gerontol A Biol Sci Med Sci · 2026 May · PMID 42152189 · Publisher ↗
BACKGROUND: Different stressors may impact physical resilience differently (resiliencies). Objective metrics assessing different stressors' 'relevance' on associated resiliencies are lacking. We propose an approach for d...
BACKGROUND: Different stressors may impact physical resilience differently (resiliencies). Objective metrics assessing different stressors' 'relevance' on associated resiliencies are lacking. We propose an approach for defining relevance metrics and potential moderating effects of sex and mortality on gait speed resiliencies. METHODS: Among 1,559 ARIC participants (age 66-80 years) with "good" gait speed (≥1 m/s), 864 (55%) maintained good gait speed at follow-up (mean 6.5 years). Gait speed resiliencies were defined using 11 intermediary stressors (stroke, cancer, depression, etc.). Each stressor's relevance was examined using Relative Ratios (RRs, 95% CI), comparing the prevalence of maintaining good gait speed among those experiencing the stressor (resilience) against the prevalence among those without the stressor, adjusting for demographics and BMI. Mortality effects and sex differences were examined. RESULTS: Stressor relevance varied from greatest (self-reported poor health: RR = 0.41, (95%CI: 0.26,0.65), 59% reduction in maintaining good gait speed), to least influential (poor social support RR = 1.02 (0.89,1.18)), with 6/11 stressors supported as relevant. Mortality and sex-differences were present; an intermediary fall was more relevant for women, where maintaining good speed versus dying was 76% less likely after a fall, RRWomen=0.24 (0.12,0.50), compared to men, RRMen=0.75 (0.39,1.44), yielding a 67% lower chance of women having good speed versus dying after a fall than men, relevance RR-ratio = (RRWomen/RRMen)=0.33 (0.12,0.86). CONCLUSIONS: Studies of physical resilience should use objective metrics to examine the relevance/importance of different combinations of stressors and functional outcomes when defining physical resiliencies. The relevance of gait speed resiliencies can vary by stressors, mortality inclusion in resiliencies, and sex.
Association between air pollution and the risk of cognitive frailty: insights from two population-based studies in the United Kingdom and China.
Deng L, Wu Y, Qiu S … +15 more , Melli G, Yue J, Li G, Zuo J, Ma R, Hao X, Huang W, Wei C, Jin Y, Zhou X, Zhang Z, Zeng B, Li Y, Zuoqiu S, Dong B
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42152187 · Publisher ↗
BACKGROUND: Cognitive frailty, encompassing cognitive decline and physical frailty, is an increasing concern in aging populations. Air pollution is associated to several health outcomes. METHODS: Data of 62 098 participa...
BACKGROUND: Cognitive frailty, encompassing cognitive decline and physical frailty, is an increasing concern in aging populations. Air pollution is associated to several health outcomes. METHODS: Data of 62 098 participants from UK Biobank cohort and 3321 participants from West China Health and Aging Trend (WCHAT) cohort were subjected to cross-sectional analyses to evaluate the association between the investigating parameters, and prospective analyses were performed in the UK Biobank. RESULTS: Exposure to ambient air pollution was significantly associated with increased risk of cognitive frailty in middle-aged and older adults. In the UK Biobank prospective analysis, exposures to NOx (hazard ratio [HR] 1.11, 95% confidence interval [CI], 1.01-1.23; p = .0357), nitrogen dioxide (HR 1.14, 95% CI, 1.00-1.30; p = .0428), and PM2.5 (HR 1.18, 95% CI, 1.04-1.34; p = .0091) were consistently associated with cognitive frailty. Cross-sectional analyses in the UK Biobank supported these findings, with additional positive associations observed for PM10 (odds ratio [OR] 1.02, 95% CI, 1.00-1.05; p = .0374). In WCHAT cohort, ozone exposure showed the most consistent associations across exposure windows and models (3-year: OR 1.29, 95% CI, 1.14-1.45; p < .0001; 5-year: OR 1.34, 95% CI, 1.20-1.50; p < .0001). Additionally, PM2.5 exposure within the 1-year exposure window also demonstrated a statistically significant association (Q3: OR 1.53, 95% CI, 1.04-2.25; p = .0327). Stratified analyses suggested stronger associations among adults ≥60 years, females, and overweight individuals. CONCLUSIONS: Higher air pollution levels were significantly associated with increased cognitive frailty risk, emphasizing on developing public health interventions to reduce air pollution exposure, especially among vulnerable populations.
Transcranial direct current stimulation targeting the left dorsolateral prefrontal cortex increases gamma power and standing balance in older adults.
Kahya M, Lo OY, Zhou J … +4 more , Cappon D, Pascual-Leone A, Lipsitz LA, Manor B
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42152186 · Publisher ↗
BACKGROUND: Standing is a complex task often performed concurrently with a cognitive task. This type of "dual-tasking" requires attentional processing and related patterns of brain activation, particularly in the gamma f...
BACKGROUND: Standing is a complex task often performed concurrently with a cognitive task. This type of "dual-tasking" requires attentional processing and related patterns of brain activation, particularly in the gamma frequency band of electrographic electroencephalography (EEG) signals (30-50 Hz). In older adults, transcranial direct current stimulation (tDCS) designed to facilitate the excitability of the left dorsolateral prefrontal cortex (L-DLPFC) improves attentional control and dual-task standing performance when tested just after stimulation. However, the effects of tDCS on underlying brain activity during single- and dual-task standing are unknown. METHODS: Thirty older adults completed three visits during which they received 20 min of tDCS targeting the L-DLPFC, the primary sensorimotor cortex (SM1, active control), or sham (inactive control) in randomized order. Before and immediately after each stimulation session, 32-channel EEG and body-worn motion sensors were used as participants completed trials of standing with and without verbalized serial subtractions. RESULTS: tDCS targeting L-DLPFC, as compared to SM1 and sham stimulation, increased gamma power during single-task standing in the anterior left (p = .02) and anterior right regions (p = .03). A similar trend (p = .08) towards increased gamma power in these regions following tDCS targeting the L-DLPFC was also observed during dual-task standing. Participants who demonstrated a greater increase in gamma power after tDCS targeting L-DLPFC exhibited greater reduction (improvement) in postural sway during single-task standing (r = -0.53, p = .007) and dual-task standing (r = -0.51, p = .003). CONCLUSIONS: These results suggest that tDCS designed to facilitate L-DLPFC excitability modulates gamma power during single-task standing, which was in turn correlated with improved postural control, in older adults.
Exploring mitochondrial genetic features in intervertebral disc degeneration through multi-omics integration analyses.
Xu F, Wang C, Sun M … +6 more , Shi S, Wang X, Liu D, Yu L, Xi C, Kong P
J Gerontol A Biol Sci Med Sci · 2026 May · PMID 42118116 · Publisher ↗
The mitochondrial genetic basis of intervertebral disc degeneration (IVDD) remains incompletely understood. This study employed multi-omics Mendelian randomization (MR) analysis to investigate the potential mitochondrial...
The mitochondrial genetic basis of intervertebral disc degeneration (IVDD) remains incompletely understood. This study employed multi-omics Mendelian randomization (MR) analysis to investigate the potential mitochondrial-related genetic mechanisms underlying IVDD. Using two-sample MR, we integrated and analyzed multi-omics quantitative trait loci, encompassing methylation, expression, protein abundance, and mitochondrial DNA, from genome-wide association studies (GWAS). Genetic associations with IVDD were obtained from the FinnGen study for discovery and the GWAS Catalog database for validation, with Steiger filtering and co-localization analysis further performed to strengthen causal inference. Additionally, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and drug prediction analyses were comprehensively employed to identify potential therapeutic targets. Our multi-omics evidence identified 23 genes, among which 5 genes (glycine amidinotransferase [GATM], SLC25A13, acyl-CoA dehydrogenase short [ACADS], TSFM, and ATP23) showed tier 1 evidence for IVDD, with GATM demonstrating the strongest support. MR analysis revealed that a higher level of GATM was associated with a reduced risk of IVDD (odds ratio: 0.934, 95% confidence interval, 0.887-0.983). Furthermore, 15 drugs targeting GATM were identified, with HYDRONIDONE completing molecular docking. Through the integration of multi-omics data, we identified 5 promising therapeutic targets for IVDD, with GATM exhibiting the most consistent multi-omics signal, and discovered 15 drugs targeting GATM and 11 drugs targeting ACADS.
Widowhood, immune aging, and mortality in older Americans: evidence from the US Health and Retirement Study.
Bae Y, Zhang Y, Chin JJY … +5 more , Tanner KT, Noppert GA, Stebbins RC, Belsky DW, Aiello AE
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42116600 · Publisher ↗
BACKGROUND: Widowhood has been linked to increased mortality risk, particularly among men, but the biological mechanisms remain unknown. Given the impacts of stress on immune function, we hypothesized that widowhood lead...
BACKGROUND: Widowhood has been linked to increased mortality risk, particularly among men, but the biological mechanisms remain unknown. Given the impacts of stress on immune function, we hypothesized that widowhood leads to increased mortality by impacting immunity. METHODS: Data from 8410 US adults aged 56 and older in the Health and Retirement Study, including flow cytometry of blood samples, survey data, and mortality, were analyzed. Associations between widowhood, immunosenescence (measured by the CD8+:CD4+ Ratio, EMRA CD4+:Naïve CD4+ Ratio, EMRA CD8+:Naïve CD8+ Ratio), and mortality were examined using linear regression and Cox proportional hazards models. RESULTS: Men and women who experienced widowhood and who showed signs of more advanced immune-system aging were at increased mortality risk. Widowed men consistently had more aged T-cells than married men across multiple measures. However, among widowed women, this association was observed only for the EMRA CD4+:Naïve CD4+ ratio. Elevated levels of aged T-cells partially mediated the relationship between widowhood and mortality, with a stronger mediating effect observed in men than in women. CONCLUSIONS: Our findings indicate that bereavement accelerates immunosenescence, contributing to the increased mortality risk observed in widowed men and revealing a biologically grounded pathway with potential for amelioration.
Sleep pattern clusters, physical function and fall risk: geriatric syndromes among older ambulatory women.
Garduno AC, Viswanath V, Smarr B … +9 more , McEvoy L, Xiao Q, Full K, Gallo L, Parada H, Crandall C, Cauley J, Tinker LF, LaCroix AZ
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42116597 · Full text
BACKGROUND: Poor sleep is a suspected risk factor for lower physical functioning and frequent falling at older ages. We evaluated the relationship of multiple sleep and rest-activity rhythm (RAR) metrics with fall risk a...
BACKGROUND: Poor sleep is a suspected risk factor for lower physical functioning and frequent falling at older ages. We evaluated the relationship of multiple sleep and rest-activity rhythm (RAR) metrics with fall risk and physical functioning. METHODS: Older women (N = 4543) wore hip-worn accelerometers, recording their falls daily for 13 months following accelerometry. Uniform manifold approximation projection identified sleep-circadian clusters; K-means clustering further distinguished healthy and unhealthy sleep patterns. After cross-validation, we examined associations between sleep clusters and fall risk using adjusted, negative binomial models. Linear regression models estimated associations of sleep clusters with short physical performance battery (SPPB) score and its sub-scores. We evaluated whether SPPB status modified associations of sleep and RAR with fall risk. RESULTS: Five sleep clusters were identified including C1 ("sleep disturbed," n = 1051), C2 ("healthy," n = 1043), C3 ("mild RAR, active," n = 1446), C4 ("earlier sleepers, n = 105), and C5 ("shorter, mildly disrupted, later sleeper," n = 898). Unhealthy sleep clusters C1 and C4 were associated with a higher fall risk compared to healthy cluster C2 after adjustment (C4, IRR: 1.76 (95% CI: 1.15-2.69)). These same clusters were also associated with lower balance scores (score: 0-4) after adjustment (C1, beta: -0.11 (95% CI: -0.21 to -0.01); C4, beta: -0.30 (95% CI: -0.55 to -0.05)). CONCLUSIONS: Older women with unhealthier sleep-RAR patterns are more at risk for falling, which may be partially explained by the role of sleep on balance and physical functioning.
Olfaction and muscle strength in older adults: a longitudinal study.
Liu R, Chen H, Li C … +3 more , Kucharska-Newton A, Simonsick EM, Yuan Y
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42116594 · Full text
BACKGROUND: Olfactory impairment is common in older adults and has been linked to weight loss and functional decline. This study aimed to examine whether olfactory impairment is associated with an accelerated decline in...
BACKGROUND: Olfactory impairment is common in older adults and has been linked to weight loss and functional decline. This study aimed to examine whether olfactory impairment is associated with an accelerated decline in muscle strength among older adults. METHODS: We analyzed data from 2348 participants (aged 71-82 years; 48.0% men; 37.5% Black) in the Health, Aging, and Body Composition Study. Olfactory function was assessed using the Brief Smell Identification Test at the Year 3 clinical visit (1999-2000) and categorized as good (scores 11-12), moderate (9-10), hyposmia (7-8), or anosmia (0-6). Participants were followed for up to 7 years. Grip strength and quadriceps strength were measured at clinical visits in Years 4, 6, 8, and 10. RESULTS: During follow-up, participants with anosmia experienced a faster decline in grip strength than those with good olfaction. The annual difference in decline was -0.19 kg/year (95% confidence interval [CI], -0.37 to -0.01) for men and -0.21 kg/year (95% CI, -0.37 to -0.05) for women. For quadriceps strength, men with anosmia had a greater annual decline (-1.26 Nm/year; 95% CI, -2.26 to -0.26), whereas no statistically significant association was observed in women. CONCLUSIONS: Anosmia in older adults is associated with accelerated decline in muscle strength. These findings suggest that olfactory impairment may serve as an early marker of neuromuscular aging. Further research is warranted to investigate the underlying mechanisms.
Trajectories of cognitive performance in the six months after hospitalization with COVID-19 among community-dwelling older adults.
Li J, McAvay G, Kaminski TA … +4 more , Gill TM, Cohen AB, Ferrante LE, Hajduk AM
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42112607 · Publisher ↗
BACKGROUND: Older adults are vulnerable to post-COVID-19 cognitive impairment (CI). This study aimed to characterize cognitive trajectories among older adults in the 6 months after hospitalization with COVID-19 and ident...
BACKGROUND: Older adults are vulnerable to post-COVID-19 cognitive impairment (CI). This study aimed to characterize cognitive trajectories among older adults in the 6 months after hospitalization with COVID-19 and identify associated factors. METHODS: This prospective longitudinal cohort study included 311 community-dwelling adults age ≥60 years hospitalized with COVID-19 and enrolled in the VALIANT (COVID-19 in Older Adults: A Longitudinal Assessment) study between June 2020 and June 2021. Cognitive performance was assessed using the Montreal Cognitive Assessment 5-min protocol during hospitalization and at 1, 3, and 6 months post-discharge. Sociodemographic and clinical data were collected via baseline interviews and the electronic health record. Cognitive trajectories and their associated factors were identified using discrete mixture models and multinomial logistic regression. RESULTS: Mean age was 71.4 ± 8.4 years (54.6% women, 3.7% with documented evidence of pre-admission CI, 41% with in-hospital CI). Three cognitive trajectories were identified at 6 months post-discharge: persistent moderate impairment (14.1%), borderline impairment (47.5%), and no impairment (38.4%). Factors associated with membership in persistent moderate or borderline impairment trajectories, relative to the no impairment trajectory, were in-hospital cognitive performance, delirium, hearing impairment, and multimorbidity. Pre-admission CI perfectly predicted membership in the no impairment trajectory (ie, zero participants in the no impairment trajectory had pre-admission CI). CONCLUSIONS: Distinct cognitive trajectories of persistent moderate impairment, borderline impairment, and no impairment emerged among older adults during the 6 months after hospitalization for COVID-19. Trajectory membership was predicted by several clinical factors, screening for which may be useful in predicting cognitive trajectories after COVID-19 hospitalization.
Turning as a single and dual task-associations with Alzheimer's and vascular pathologies in cognitively healthy older people.
Nilsson MH, Lindh-Rengifo M, Rochester L … +6 more , Van Westen D, Smith R, Palmqvist S, Stomrud E, Mattsson-Carlgren N, Hansson O
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42109046 · Full text
BACKGROUND: Turning performance is an important and challenging motor activity, with potential relevance in several brain diseases. This study aimed to determine how Alzheimer's and vascular pathologies are associated wi...
BACKGROUND: Turning performance is an important and challenging motor activity, with potential relevance in several brain diseases. This study aimed to determine how Alzheimer's and vascular pathologies are associated with turning (360° while standing and 180° while walking), both as a single task and during dual-tasking in cognitively healthy older people. METHODS: Cognitively healthy older people (n = 297, mean age 77.7 years, 61.6% women) were included. A 180° turn was assessed using a wearable sensor; a 360° turn was assessed both clinically and using a sensor. Dual-tasking included a simultaneous subtraction task. Alzheimer's pathologies (Aβ and tau) were assessed using positron emission tomography (PET). Vascular pathology (white matter hyperintensities (WMH)) was assessed using magnetic resonance imaging (MRI). Logistic and linear regression analyses were used. RESULTS: Aβ and tau pathologies were significantly associated with being unstable while dual-tasking and turning 360°. When including both Aβ and tau in the model, only tau remained significantly associated with being unstable (OR 22.42, 95% CI, 1.43, 349.88, p = .027). WMH were associated with impaired turning as a single task, that is, an increased turn duration (360°) and a decreased peak angular velocity (180°: B -1.27, 95% CI, -2.33, -0.21, p = .018). CONCLUSIONS: This study suggests that early Alzheimer's pathologies are associated with an instability while turning 360° and dual-tasking, whereas WMH seem to be associated with impaired turning as a single task in cognitively healthy older people. Turning assessments seem promising for investigating motor aspects in very early stages of Alzheimer's disease and vascular brain disease.
Association and predictive value of biological aging for chronic kidney disease risk in diabetes: cross-cohort validation across the United Kingdom and China.
Wu Y, Xiang H, Huang Y … +12 more , Zhang Y, Ye Z, Zhang Y, Yang S, Gan X, Zhang Y, Chen D, Cai X, Liang X, Nie S, Hou FF, Qin X
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42104203 · Publisher ↗
Biological aging (BA) may influence chronic kidney disease (CKD) development. We evaluated the association of accelerated BA-quantified using Klemera-Doubal method biological age (KDM-BA) and phenotypic age (PhenoAge)-wi...
Biological aging (BA) may influence chronic kidney disease (CKD) development. We evaluated the association of accelerated BA-quantified using Klemera-Doubal method biological age (KDM-BA) and phenotypic age (PhenoAge)-with incident CKD, and assessed its predictive value beyond conventional risk factors (CKD Prediction Consortium [CKD-PC] model) in participants with diabetes. This two-country cohort study included 14 274 participants with diabetes from the UK Biobank and 7900 from the China Renal Data System (CRDS). KDM-BA and PhenoAge were calculated from clinical biomarkers, and their acceleration (deviation from chronological age) was evaluated. Cox regression assessed associations with incident CKD, while C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) evaluated predictive performance. Over median follow-ups of 13.3 (UK Biobank) and 3.3 (CRDS) years, 1676 and 709 incident CKD cases were documented. Each standard deviation increase in KDM-BA acceleration was associated with 31% (95% CI: 23%-39%) (UK) and 68% (95% CI: 58%-80%) (China) higher CKD hazard. PhenoAge acceleration similarly increased CKD risk (29% and 28%, respectively). In the UK Biobank, adding KDM-BA or PhenoAge acceleration to the CKD-PC model (C-index = 0.770) led to modest but statistically significant improvements in prediction (C-index increase = 0.004 [95% CI: 0.002-0.006] and 0.003 [0.001-0.005], respectively), while leukocyte telomere length (LTL) provided no benefit (0.0001 [-0.0004, 0.0005]). Both BA measures enhanced reclassification (NRI: 0.034-0.076; IDI: 0.002-0.003). CRDS analyses yielded consistent results. Accelerated BA is consistently associated with higher CKD hazard in diabetes across European and Asian populations. KDM-BA and PhenoAge offer practical tools for refining CKD risk stratification.
A pragmatic three-component clinical score for cognitive risk stratification in older adults with multimorbidity and frailty.
Mozid NE, Monju IH, Sharmin S … +1 more , Ahmed SB
J Gerontol A Biol Sci Med Sci · 2026 May · PMID 42097303 · Publisher ↗
BACKGROUND: Simple, scalable clinical tools are needed to identify older adults with cognitive impairment in low-resource settings, yet whether parsimonious approaches can match complex phenotyping methods remains unclea...
BACKGROUND: Simple, scalable clinical tools are needed to identify older adults with cognitive impairment in low-resource settings, yet whether parsimonious approaches can match complex phenotyping methods remains unclear. This study developed a three-component clinical score and compared its discriminative performance with latent class analysis (LCA)-derived multimorbidity phenotypes. METHODS: This cross-sectional study included 504 Bangladeshi community-dwelling adults aged ≥65 years with at least one chronic disease. Frailty was assessed using the Fried phenotype, and multimorbidity was self-reported and coded using International Classification of Diseases, 10th Revision. An additive score (0-5 points) incorporating age ≥80 years, ≥3 chronic conditions, and frailty classified participants into low (0-1), moderate (2-3), or high (4-5) risk. Outcomes included global cognition and cognitive impairment (Mini-Mental State Examination [MMSE] < 25). RESULTS: The three-component score showed acceptable discrimination for cognitive impairment (area under the curve [AUC] = 0.72) and explained 33% of MMSE variance. LCA-derived phenotypes demonstrated poor discrimination (AUC = 0.44; difference = 0.28, p < .001). A monotonic gradient was observed across risk categories, impairment prevalence increased across risk categories (59%, 83%, and 96%), corresponding to a 12.8-point MMSE difference across the score range. A frailty-augmented LCA (in which frailty was added to the original disease-only LCA) combined with age yielded a modestly higher AUC (0.764), though at substantially greater analytical complexity. CONCLUSIONS: A parsimonious clinical score combining age, multimorbidity, and frailty demonstrated acceptable cross-sectional discrimination for prevalent cognitive impairment and substantially outperformed disease-only multimorbidity phenotyping. Subject to prospective validation, this pragmatic tool may support case-finding and cognitive risk stratification in resource-limited settings.
Evidence for an energy conservation model of inflammaging and immunosenescence in the US Health and Retirement Study and UK Biobank.
Aronoff JE, Franck M, Cohen AA … +1 more , Trumble BC
J Gerontol A Biol Sci Med Sci · 2026 Jun · PMID 42096840 · Full text
The development of chronic inflammation in later life (inflammaging), alongside changes in immune cell profiles and impaired pathogen defense (immunosenescence), contribute to health risk. However, these processes have b...
The development of chronic inflammation in later life (inflammaging), alongside changes in immune cell profiles and impaired pathogen defense (immunosenescence), contribute to health risk. However, these processes have been hypothesized as adaptive remodeling of the immune system in response to accumulating somatic damage. Here we consider a recently developed theoretical framework to understand their relationship: the Brain-Body Energy Conservation model of aging. This model views immunosenescence as part of an energy conserving response to the rising energy expenditure of inflammaging. This response promotes short-term survival against somatic damage at the expense of future health risk. For example, naïve T cells, which enhance defense against future infections, decline with age, while proteins that suppress the immune response to infection, including interleukin (IL)-10, increase. GDF-15, which similarly suppresses the immune response to infection and is produced in response to chronic inflammation and metabolic stress, also increases with age. We find evidence consistent with this model in the US Health and Retirement Study (HRS, n = 8 184) and UK Biobank (UKB, n = 40 510). Across both cohorts, the key inflammaging marker tumor necrosis factor receptor (TNFR1) partially mediated the age-related increases in IL-10 and GDF-15. In the HRS flow cytometry data, TNFR1 also mediated age-related decreases in naïve T cells. Finally, we assessed vulnerability to a novel future infection using the UKB medical records data on hospitalization or death from COVID-19 (n = 586 hospitalized or died). TNFR1, IL-10, and GDF-15, measured pre-pandemic, all partially mediated the age-related increased risk.
Finding the turning point in aging: a comparison of physical, cognitive, and psychological trajectories among centenarians and non-centenarians.
Zhao E, Ailshire JA, Kim JK … +1 more , Crimmins EM
J Gerontol A Biol Sci Med Sci · 2026 May · PMID 42096826 · Full text
BACKGROUND: Centenarians tend to delay age-related decline until very late life and generally experience slower deterioration across health domains. However, timing and pace of decline across physical, cognitive, and psy...
BACKGROUND: Centenarians tend to delay age-related decline until very late life and generally experience slower deterioration across health domains. However, timing and pace of decline across physical, cognitive, and psychological domains among centenarians, compared to other long-lived groups, remain poorly characterized. METHODS: Using the nationally representative Health and Retirement Study (1993-2022), we modeled trajectories of disease burden, physical functioning, psychological wellbeing, and cognition among participants born before 1922 (N = 7237), followed up to 29 years. Participants were categorized by survival groups: centenarians (100+), nonagenarians (90-99), octogenarians (80-89), and septuagenarians (73-79). Joinpoint regression identified ages at which decline accelerated and quantified rates of change. RESULTS: Those who lived to older ages-nonagenarian and centenarian decedents-maintained higher levels of physical/cognitive functioning into later life but showed sharp accelerations thereafter. Across physical functioning and cognition, onset of accelerated decline shifted later among those who survived longer, with centenarians showing the latest age at acceleration. Prior to acceleration, activities of daily living/instrumental activities of daily living limitations increased by approximately 0.04-0.05 points per year, rising to 0.20-0.34 points per year thereafter, while prevalence of cognitive impairment accelerated from roughly 1% to 4%-6% per year. Individuals who survived longer also maintained lower depressive symptoms and disease burden into advanced ages, although cardiovascular conditions continued to rise. CONCLUSIONS: Exceptional longevity is marked by preserved physical and cognitive function followed by rapid late-life declines. Pinpointing when this tipping point occurs offers a quantitative basis for targeting interventions-medical, behavioral, and social-that sustains function and delay deterioration at the population level.
Developing and internally validating AI-based aging resilience biomarkers in non-human primates.
Bennett RF, Speiser JL, Olson JD … +5 more , Schaaf GW, Register TC, Cox LA, Cline JM, Quillen EE
J Gerontol A Biol Sci Med Sci · 2026 May · PMID 42093008 · Full text
Quantifying biological aging is crucial for understanding functional decline before the onset of morbidity. While many accelerated aging and frailty measures based on clinical data exist for humans and several for rodent...
Quantifying biological aging is crucial for understanding functional decline before the onset of morbidity. While many accelerated aging and frailty measures based on clinical data exist for humans and several for rodent models of aging, there are few options for non-human primates (NHPs). NHP clinical data has several unique features including a lack of clinically delineated normative values for features and variability in data collection over long lifespans. There are also wide discrepancies in the number of available clinical measures and the number of animals across data sets. To address these challenges, we developed and validated "aging resilience" (AR) metrics using longitudinal, routine clinical data from two distinct non-human primate cohorts: 4328 baboons and 281 rhesus macaques. We trained five computational models-including Linear Mixed-Effects Models, Random Forest, and Recurrent Neural Networks (RNN)-to predict chronological age, subsequently deriving AR metrics that represent the velocity (rate of aging) and cumulative burden (normalized cumulative aging) of physiological deviation. While linear models achieved high precision in predicting chronological age (test R2 up to 0.99), they correlated poorly with actual lifespan. In contrast, AR metrics derived from non-linear models (RNN and Random Forest) displayed strong predictive validity for mortality (Pearson's r > 0.8). These findings highlight a critical paradox: models that best predict chronological age do not necessarily capture the biological resilience determining healthspan. This study establishes a scalable framework for monitoring biological aging in translational models using standard veterinary records.
The effects of high-intensity interval training versus continuous moderate-intensity exercise on body composition among older adults with HIV.
Kulik GL, Oliveira VHF, Wilson MP … +8 more , Khuu V, Jankowski CM, Dillon S, Cook P, MaWhinney S, Ghosh D, Webel AR, Erlandson KM
J Gerontol A Biol Sci Med Sci · 2026 May · PMID 42080214 · Full text
We compared two exercise intensities on lean and fat mass among older people with HIV (PWH). The High Intensity Exercise to Attenuate Limitations and Train Habits (HEALTH) randomized sedentary PWH ≥50 years to 16 weeks o...
We compared two exercise intensities on lean and fat mass among older people with HIV (PWH). The High Intensity Exercise to Attenuate Limitations and Train Habits (HEALTH) randomized sedentary PWH ≥50 years to 16 weeks of high-intensity interval training (HIIT) or continuous moderate-intensity exercise (CME), both with resistance exercise. Body composition was measured using dual-energy x-ray absorptiometry (DXA) at baseline and week 16. The primary outcome was the percent change in body fat percentage (ratio of fat mass to total mass). Secondary outcomes included percent change in lean, fat, appendicular lean (ALM), and total mass. Linear regression models examined between- and within-group changes from baseline to week 16. Of the 95 participants with pre- and post-DXA scans, the median (interquartile range [IQR]) age was 58 [54-61] years, 14% female, 14% Black, and 14% Hispanic. Fat percentage decreased by -3.3% (95% confidence interval [CI]: -5.2, -1.6) in HIIT and -3.3% (95% CI: -5.3, -1.6) in CME. Fat mass decreased by -3.5% (95% CI: -5.9, -1.0) in HIIT and -3.8% (95% CI: -6.3, -1.3) in CME. Lean mass increased by 1.7% (95% CI: 0.7, 2.7) and ALM by 3.3% (95% CI: 1.3, 5.3) in HIIT and 1.2% (95% CI: 0.2, 2.2) and ALM by 2.6% (95% CI: 0.6, 4.6) in CME. Although both arms had significant improvements compared to baseline, no between-arm comparisons were statistically significant. Supervised HIIT or CME combined with resistance training for 16 weeks is an effective strategy for improving body composition in previously sedentary older PWH. Clinicaltrials.gov: NCT04550676.
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