The Journals Of Gerontology. Series A, Biological Sciences And Medical Sciences[JOURNAL]
Sun
200 papers
Striatal dopamine and skeletal muscle energy metabolism in older adults.
Rosano C, Bohnen NI, Lopresti B … +8 more , Chahine LM, Barnes HN, Studenski SL, Glynn NW, Newman AB, Marcinek DJ, Hepple RT, Coen PM
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41691472 · Full text
BACKGROUND: Dopamine (DA) in the central nervous system is considered a master regulator of mobility performance and vigor, but its mechanistic relationship with skeletal muscle energetics is unclear. METHODS: We tested...
BACKGROUND: Dopamine (DA) in the central nervous system is considered a master regulator of mobility performance and vigor, but its mechanistic relationship with skeletal muscle energetics is unclear. METHODS: We tested the cross-sectional association of striatal DA and skeletal muscle mitochondrial function in 146 older adults participating in the Study of Muscle, Mobility and Aging (75.4 years old, 54% women). Striatal DA was measured using (+)-a-[11C] dihydrotetrabenazine (DTBZ) PET imaging for the limbic, sensorimotor, and executive control subregions. Mitochondrial capacity to produce ATP (ATPmax, mM ATP/s) was measured in vivo using 31P magnetic resonance spectroscopy after repeated voluntary muscle contractions. Ex-vivo respirometry assays from biopsies of resting muscle captured complementary aspects of mitochondrial function under optimal conditions. RESULTS: In multivariable linear regression models, [11C]DTBZ in the limbic striatum, but not other subregions, was positively associated with greater ATPmax in vivo, independent of demographics, muscle volume, leg power, white matter hyperintensities, gray matter atrophy, moderate-to-vigorous physical activity and diabetes (β = 0.275, standard error 0.108, p = .019). [11C]DTBZ was not associated with the ex-vivo mitochondrial respiration markers (p > .2). CONCLUSIONS: The role of striatal limbic DA and the energetic capacity of skeletal muscles should be further investigated in older adults.
Development and validation of cardiorespiratory fitness prediction equations from 6-minute walk test: the Coronary Artery Risk Development in Adults (CARDIA) study.
Hornikel B, Dooley EE, Bowling CB … +9 more , Chen B, Martinez-Amezcua P, Jacobs DR, Carnethon M, Sternfeld B, Lewis CE, Sidney S, Palta P, Gabriel KP
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41691466 · Full text
BACKGROUND: Assessing maximal oxygen consumption (VO2max), the gold standard for assessing cardiorespiratory fitness, is often impractical in large-scale studies. We derived sex-specific VO2 max and graded exercise test...
BACKGROUND: Assessing maximal oxygen consumption (VO2max), the gold standard for assessing cardiorespiratory fitness, is often impractical in large-scale studies. We derived sex-specific VO2 max and graded exercise test duration (GXTd) prediction equations from 6-minute walk test (6MWT) performance. METHODS: Data were from 564 Coronary Artery Risk Development in Young Adults (CARDIA) participants (mean age: 61.5 years; 58% women; 40% Black) who completed the 6MWT and symptom-limited modified Balke treadmill graded exercise test at the Year 35 (2021-2022) follow-up exam. Sex-stratified samples were randomly split (2/3 for training, 1/3 for testing) to derive and evaluate prediction equations. Stepwise linear regression identified predictors of VO2max and GXTd from 6MWT distance. Sex-specific VO2max CARDIA equations were compared with Burr and FRIEND equations. Models' accuracies were evaluated by comparing the predicted values to measured values using Student's t-test and Pearson correlation coefficients (r). Bland-Altman plots used to evaluate agreement between measured and predicted values. RESULTS: Sex-specific VO2max CARDIA equations explained 53% and 57% of the variance in men and women, respectively, with strong correlations between measured and predicted values (r = 0.73 and 0.78). The Burr and FRIEND equations showed larger biases and weaker correlations compared with the CARDIA equations. The GXTd equations explained 59% and 62% of the variance in men and women, with strong correlations (r = 0.71 and 0.72) and no significant mean differences between observed and predicted. CONCLUSIONS: The CARDIA prediction equations for VO2max and GXTd from 6MWT enhance accuracy and accessibility, providing a practical tool for large-scale studies and clinical assessments, particularly in aging populations.
Biomarkers help us understand how cellular and systemic aging contribute to mortality: a study utilizing a machine-learning approach in the Health and Retirement Study.
Klopack ET, Crimmins EM
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41691465 · Full text
BACKGROUND: Research suggests aging is a coordinated physiological decline occurring in multiple systems and at multiple biological levels. However, it is largely unknown how general biological aging and specific systemi...
BACKGROUND: Research suggests aging is a coordinated physiological decline occurring in multiple systems and at multiple biological levels. However, it is largely unknown how general biological aging and specific systemic aging co-occur and influence one another to affect health outcomes. There is also emerging interest in understanding how social exposures may differentially accelerate decline in individual physiological systems. METHODS: We utilize data from the Health and Retirement Study, a nationally representative sample of about 4000 US adults over age 55. We used eXtreme Gradient Boosting (xgboost) in a training subsample to create system-specific mortality risk scores based on sets of biomarkers representing biological systems (eg, brain and nervous system, adaptive immune system, cardiovascular system, renal system) as well as general multisystem aging. RESULTS: Results suggest that the effects of most biological systems may be well captured by one or a small number of biomarkers and that female sex appears to be a protective or risk factor depending on specific biological system. CONCLUSIONS: The importance of studying both general and system-specific aging is discussed.
Benefits of oral nitrite supplementation on mitochondrial respiration and physical function in older adults.
Forman DE, Perera S, Shiva S … +14 more , Glynn NW, Stakich TS, Ramos SV, Distefano G, Wolf C, Kendi A, Sterczala AJ, Sipula IJ, Bello FM, Jurczak MJ, Sciurba FC, Gladwin MT, Newman AB, Coen PM
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41691463 · Full text
BACKGROUND: Age-associated decline in mitochondrial oxidative capacity is associated with increased risk of disease, frailty, and disability. Oral nitrite and nitrate supplementation have been demonstrated to improve mit...
BACKGROUND: Age-associated decline in mitochondrial oxidative capacity is associated with increased risk of disease, frailty, and disability. Oral nitrite and nitrate supplementation have been demonstrated to improve mitochondrial energetics and physical function in younger adults, but effects in older adults (age ≥70 years) remain unclear. METHODS: We conducted a randomized, placebo-controlled, double-blind, two-arm trial with a parallel group design to examine the effect of 20 mg sodium nitrite supplements administered three times a day for 12 weeks versus placebo in older (age ≥70 years) sedentary adults. Change in muscle mitochondrial respiration (complex I and II supported maximal oxidative phosphorylation [CI&II MaxOXPHOS]) was the primary outcome. Platelet bioenergetics, cardiorespiratory fitness, and other physical function measures were also assessed. RESULTS: Sixty-four adults (75.7 ± 5.7 years) completed the trial. Nitrite supplementation was not associated with improvements in skeletal muscle mitochondrial respiration, nor improvements in exercise capacity and physical function. However, platelet mitochondrial respiration changed significantly following an acute dose of oral nitrite. Notably, while nitrite levels increased 16- to 30-fold in plasma following an acute dose, levels increased only 1.6-fold in skeletal muscle. CONCLUSIONS: The divergent response of skeletal muscle versus platelet mitochondrial respiration in response to nitrite supplementation suggests tissue-specific pharmacokinetics and pharmacodynamics that likely impact the efficacy of nitrite supplementation. Results also suggest there may be age-related changes in drug delivery, metabolism, and mitochondrial responsiveness compared to the effects of nitrite/nitrate previously demonstrated in younger adults. Clinical Trial Registration Number: ClinicalTrials.gov NCT04405180.
Associations of unmet dental care needs due to cost with incident cardiovascular disease and dementia: a prospective study in the All of Us cohort.
Velez M, Buto PT, Pederson AM … +5 more , Weuve J, Murchland AR, Wang J, Glymour MM, Sims KD
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41678708 · Full text
BACKGROUND: Poor oral health among older adults may contribute to cardiovascular and dementia risk via systemic inflammation and cardiometabolic comorbidities. Financial constraints are a major driver of unmet dental car...
BACKGROUND: Poor oral health among older adults may contribute to cardiovascular and dementia risk via systemic inflammation and cardiometabolic comorbidities. Financial constraints are a major driver of unmet dental care needs for older individuals. This study investigates whether having dental care needs that were unmet due to cost is associated with subsequent incidence of cardiovascular disease (CVD) or dementia among adults aged 55 and older. METHODS: Participants in the All of Us cohort (N = 98 787) who responded to a survey question on dental care needs that were unmet due to cost were followed up to 5.3 years via electronic health records for onset of myocardial infarction (MI), stroke, heart failure (HF), or dementia. We estimated outcome-specific hazard ratios (HRs), using Cox proportional-hazards models, adjusting for demographic, behavioral, and clinical covariates. RESULTS: After adjustment for demographic factors, individuals who reported unmet dental needs due to cost had relatively higher incidence of HF (HR = 1.45; 95% CI, 1.30-1.63), MI (HR = 1.37; 95% CI, 1.17-1.61), stroke (HR = 1.45; 95% CI, 1.24-1.70), and dementia (HR = 1.37; 95% CI, 1.05-1.76). These associations were attenuated after further adjusting for socioeconomic, behavioral, and clinical factors. We did not observe differences by gender, racial and ethnic identity, or periodontitis diagnosis. The estimated population attributable fraction suggested that eliminating financial barriers to dental care could prevent 2%-4% of each outcome among older adults. CONCLUSION: Financial barriers to dental care may be an important determinant of CVD and dementia among aging populations.
Are aging clocks based on routine clinical indicators trustworthy and applicable? A systematic review and critical appraisal.
Zhang J, Hu J, Gao Y … +3 more , Pang Z, Mo L, Wu IXY
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41678247 · Publisher ↗
Aging clocks based on routine clinical indicators have emerged as a cost-effective tool for assessing biological age. This systematic review aims to summarize the characteristics and critically appraise these available a...
Aging clocks based on routine clinical indicators have emerged as a cost-effective tool for assessing biological age. This systematic review aims to summarize the characteristics and critically appraise these available aging clocks. Studies that developed aging clocks for adults (≥18 years) based on routine clinical indicators were retrieved from six databases (PubMed, EMBASE, Web of Science, CNKI, Wanfang Data, and Sinomed) up to June 18, 2024. The PROBAST + AI tool was used to assess the methodological quality, risk of bias, and applicability of included aging clocks. All the results were narratively summarized. Fifty-nine studies involving 81 aging clocks were included, of which 71 (87.7%) were developed using single-country datasets predominantly from China, the United States, Korea, and the United Kingdom. Notably, 31 aging clocks (38.3%) were developed with neither internal nor external validation. The majority of aging clocks were rated as having high concern regarding quality and high risk of bias, even including those published in high-impact journals. Only three aging clocks (3.7%) from two studies were rated as having low concern regarding quality and applicability during development, and two of these (4.0%) from one study further demonstrated low risk of bias and low concern for applicability during model evaluation. Future research should prioritize validating the promising aging clocks in target populations rather than developing new ones, adhere to the PROBAST + AI and TRIPOD + AI guidelines for methodological rigor and transparent reporting, and provide reproducible and user-friendly model codes and tools.
The relative effects of different exercise modes on physical and metabolic health in older adults: a network meta-analysis.
Yuan J, Li F, Shi S … +1 more , Wu Z
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41678236 · Publisher ↗
Multiple exercise modalities are recommended for older adults, yet their comparative effectiveness remains uncertain. We conducted a Bayesian network meta-analysis of randomized trials to compare common exercise modes on...
Multiple exercise modalities are recommended for older adults, yet their comparative effectiveness remains uncertain. We conducted a Bayesian network meta-analysis of randomized trials to compare common exercise modes on cardiorespiratory fitness and metabolic health in adults aged ≥55 years. Trials randomized participants to high-intensity interval training (HIIT), aerobic training (AT), resistance training (RT), combined aerobic-resistance training (CART), or non-exercise control. The primary outcome was maximal/peak oxygen uptake (VO2max/VO2peak). Secondary outcomes included BMI, body fat percentage, fat-free mass, systolic/diastolic blood pressure, and blood lipids. We fitted random-effects Bayesian network meta-analysis models and summarized ranking probabilities using the surface under the cumulative ranking curve. No exercise modality showed a clear advantage for VO2max/VO2peak; credible intervals were wide for most between-modality comparisons. Versus control, RT increased fat-free mass, CART reduced body fat percentage and systolic blood pressure, and HIIT reduced BMI and triglycerides. For total cholesterol, LDL-C, HDL-C, and diastolic blood pressure, credible intervals generally included the null. Heterogeneity was moderate, and formal inconsistency assessment was limited by sparse networks. Current evidence does not identify a single "best" exercise modality for improving VO2max/VO2peak in older adults. Modality selection may be better guided by the primary goal (eg, RT for lean mass, CART for adiposity and systolic blood pressure, HIIT for BMI and triglycerides), while considering feasibility and safety. Larger, well-reported head-to-head trials are needed to strengthen comparative estimates.
Socioeconomic and clinical predictors of all-cause mortality among older adults in India from 2017 to 2024: the importance of cognitive health and dementia.
Nichols E, Dey S, Khobragade P … +8 more , Banerjee J, Adar SD, Chien S, Gross AL, Petrosyan S, Crimmins EM, Dey AB, Lee J
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41649462 · Full text
BACKGROUND: Characterizing the correlates of adult mortality can lend insights into the factors associated with consequential health outcomes among older adults. In India, the importance of adult mortality has grown give...
BACKGROUND: Characterizing the correlates of adult mortality can lend insights into the factors associated with consequential health outcomes among older adults. In India, the importance of adult mortality has grown given trends in population aging, but prior research has been limited by a lack of high-quality longitudinal data. METHODS: We used new data from Waves 1 (2017-2019) and 2 (2022-2024) of the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) study (N = 3871) to evaluate associations between all-cause mortality and 27 socioeconomic and clinical factors using Cox proportional hazards models. We also evaluated gender differences and the impact of COVID-19. RESULTS: The estimated mortality rate was 6.0 (95% confidence intervals [95% CI]: 5.6-6.4) deaths per 100 person-years. A broad range of factors were associated with mortality, but cardiometabolic and cognitive phenotypes had some of the strongest -associations; those with dementia had a 2.84 (95% CI: 2.12-3.81) times greater risk of death than those with -normal -cognitive functioning. Associations with socioeconomic factors tended to be stronger for men than women (eg, wealth quintile; χ2 p = .046), whereas associations with clinical factors tended to be stronger for women than men (eg, diabetes; χ2 p = .033). We observed some evidence of excess mortality due to COVID-19. CONCLUSIONS: Findings emphasize the multifaceted nature of health among older adults in India and illustrate the need for solutions that recognize the importance of a wide range of social factors and clinical health conditions. Results also showcase the importance of dementia as a key factor associated with survival among older adults.
Particulate air pollution and post-discharge recovery among older adults hospitalized for heart failure in the United States.
Wen T, Hu J, Shardell M … +5 more , McCoy R, Chen S, Ryan K, Falvey J, Chen C
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41644421 · Full text
BACKGROUND: The impact of exposure to fine particulate matter (PM2.5) on post-discharge recovery in older adults already hospitalized for heart failure remains unclear. We evaluated associations between exposure to PM2.5...
BACKGROUND: The impact of exposure to fine particulate matter (PM2.5) on post-discharge recovery in older adults already hospitalized for heart failure remains unclear. We evaluated associations between exposure to PM2.5 and days spent at home (DAH) as well as mortality in a nationwide representative sample of U.S. adults aged 65 years and older. METHODS: Data from 66 854 Medicare Fee-for-service beneficiaries with heart failure hospitalization (2017-2019) were linked with validated, model-derived mean PM2.5 concentrations at Zip Code Tabulation Areas level during the month of hospital admission. Post-discharge 180-day DAH was defined as days alive minus days spent in inpatient hospitals, hospital observation units, nursing facilities, or emergency departments. All-cause mortality was assessed as time from hospital discharge to death within 180 days. Quantile regression and Cox proportional regression models, adjusted for covariates, were used to quantify associations. RESULTS: Exposure to the highest quartile PM2.5 level (>8.61 µg/m3) was associated with 5.05 fewer DAH (95% CI: -8.61, -1.48; p = .006) after discharge at the 20th percentile of DAH, compared with those exposed to the lowest PM2.5 quartile (≤5.90 µg/m3). Exposure to the highest quartile PM2.5 levels was also associated with higher risk of all-cause mortality within 180 days after hospitalization as compared to the lowest PM2.5 quartile (hazard ratio = 1.05, 95% CI: 1.004-1.10, p = .033). CONCLUSIONS: Particulate air pollution may negatively impact recovery more strongly at the lower tail of recovery than at the median or higher tail, highlighting the need for targeted intervention strategies to protect the most vulnerable patients.
Atlas of human cerebellar aging: nonlinear molecular trajectories reveal multidimensional mechanisms underlying cognitive and motor function regulation.
Ma X, Zhao L, Pan H … +8 more , Feng Z, Lin J, Ji J, Li J, Liu X, Wang J, Tang X, Li K
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41644416 · Publisher ↗
The cerebellum, traditionally recognized for motor coordination, may also contribute to cognitive and emotional regulation, as recent evidence indicates. However, the molecular and structural changes in the human cerebel...
The cerebellum, traditionally recognized for motor coordination, may also contribute to cognitive and emotional regulation, as recent evidence indicates. However, the molecular and structural changes in the human cerebellum during healthy aging remain poorly understood. This study systematically investigated the molecular trajectories and structural alterations in the human cerebellum across the adult lifespan (20-80 years) by integrating cerebella transcriptomic data from 456 non-disease brains and MRI structural neuroimaging data from 264 disease-free subjects. Fuzzy clustering analyses uncovered nonlinear expression trajectories involving synaptic plasticity, metabolic regulation, and protein homeostasis, highlighting multiple critical biological turning points across different age periods. Differential gene expression analyses identified early downregulation of immediate early genes (eg, FOS, NPAS4, EGR1-3) and sustained activation of stress-response pathways changes that precede observable functional decline. Moreover, we identified an integrated "synaptic plasticity-stress homeostasis" module, where immediate early genes and heat shock proteins exhibit coordinated regulation whose efficiency progressively declines with age. MRI analyses showed a pronounced acceleration of cerebellar gray matter (GM) loss after age 70, with multiple subregions affected, highlighting the nonlinear trajectory of cerebellar structural aging. In combination with the transcriptomic findings, these results indicate that cerebellar aging comprises complex, stage-dependent molecular alterations accompanied by GM reductions in later decades. This collective evidence advances our understanding of cerebellar aging biology and highlights the synaptic-stress module as a promising molecular axis that may inform future strategies to support cerebellar function in older adults.
Differences in blood levels of neuroligin-derived peptides in a cohort for early detection of Alzheimer's disease.
Fernandes MGF, Pinard M, Sokullu E … +5 more , Tremblay C, Gagnon JF, Calon F, Coulombe B, Brouillette J
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41639022 · Full text
Alzheimer's disease (AD) develops gradually, with significant neurodegeneration already present by the time clinical symptoms emerge. Since synapses are affected early in the disease, synaptic proteins are being investig...
Alzheimer's disease (AD) develops gradually, with significant neurodegeneration already present by the time clinical symptoms emerge. Since synapses are affected early in the disease, synaptic proteins are being investigated as potential markers of the prodromal stage. Using data and plasma samples provided by the Consortium for the early identification of Alzheimer's disease-Quebec, we analyzed plasma levels of neuroligin (NLGN)-derived peptides in cognitively normal (CN) individuals and cognitively impaired (CI) individuals, including those with amnestic mild cognitive impairment and early-stage AD. Plasma levels of NLGN-derived peptides were assessed by quantifying tryptic peptides using liquid chromatography coupled with tandem mass spectrometry. Our findings show that levels of specific NLGN peptides were significantly elevated in CI compared to CN individuals. Receiver operating characteristic curve analysis revealed that some NLGN peptides could distinguish CI individuals. Furthermore, analysis based on mini-mental state examination scores revealed that specific plasma phosphorylated tau peptides were significantly and positively correlated with selected NLGN-derived peptides in more advanced stages of cognitive decline. These results support further investigation into synaptic NLGN-derived peptides in the blood as promising tools for monitoring the earliest stages of AD.
The impact of hearing loss on annual incident age-associated dementia cases and quality of life in the United States.
Borre ED, Deleger JN, Dillard LK … +9 more , Pavon JM, Shah SJ, Dubno JR, Smith SL, Freedberg KA, Francis HW, Ritchie CS, Sanders Schmidler GD, Hyle EP
J Gerontol A Biol Sci Med Sci · 2026 Apr · PMID 41632497 · Full text
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 2...
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 microsimulation of 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.
Determinants of oral functions and oral frailty in older community-dwelling individuals: a comprehensive analysis.
Jia L, Grigoriadis A, Suzuki A … +5 more , Strandberg R, Skott P, Sandborgh Englund G, Trulsson M, Kumar A
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41627874 · Full text
BACKGROUND: Aging alters oral structures, affecting chewing and swallowing function. Oral function is increasingly recognized as an important component of systemic health outcomes in older individuals. Understanding age-...
BACKGROUND: Aging alters oral structures, affecting chewing and swallowing function. Oral function is increasingly recognized as an important component of systemic health outcomes in older individuals. Understanding age-related changes in oral function is crucial for oral health care. This study comprehensively evaluated the various oral function determinants and their age-related changes, identified key factors, and estimated the prevalence of poor oral functions. METHODS: A cross-sectional study of older individuals (n = 206) participated. Oral functions were objectively assessed through dental status, saliva secretion, orofacial muscle strength, masticatory performance, and swallowing function. Correlation analysis, cluster analysis, and multiple regression were employed to explore the complexities of oral function determinants and their interrelationships and to estimate the prevalence of poor oral functions. RESULTS: Correlation analysis showed significantly (p < .001) strong (rs = -0.79) to low (rs = -0.11) correlations between determinants of oral function. The cluster analysis successfully identified three major groups of oral function. Further, the multiple linear regression and backward elimination showed that chewing strokes, natural teeth, and tongue pressure (p < .001) were significant predictors of age. Additionally, the prevalence of older individuals with poor dental status, reduced tongue pressure strength, and low saliva secretion rate was estimated at 9.7%, 14.6%, and 8.3%, respectively. CONCLUSIONS: Oral function determinants show age-related changes and have the potential to estimate the prevalence of poor oral functions in older individuals. These findings may be critical in identifying the phenotypic profile of people with poor oral function.
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.
Li M, Thibault DP, De Lott LB … +3 more , Gravel CA, Freeman EE, Hamedani AG
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41615430 · Full text
BACKGROUND: Visual 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 ep...
BACKGROUND: Visual 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. METHODS: In 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 = 2447), 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). RESULTS: Self-reported visual difficulty was associated with depression in NHATS (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. CONCLUSIONS: Associations 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.
"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.
Oh O, Harrison S, Sefcik JS … +3 more , Richmond TS, Hodgson N, Demiris G
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41612896 · Full text
BACKGROUND: Passive 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...
BACKGROUND: Passive 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. METHODS: For 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. RESULTS: Findings 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. CONCLUSIONS: Participants 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 to build trust within the community.
RPS14 as an aging-related biomarker for early-onset alterations of testicular senescence-associated genes in spermatogenic dysfunction at childbearing age.
Dong F, Ping P, Wang SQ … +2 more , Ma Y, Chen XF
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41592225 · Publisher ↗
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 testic...
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.
Social isolation and functional impairment trajectories in a diverse cohort of middle-aged and older adults in Northern California.
Rojas-Saunero LP, Ikesu R, Zhou Y … +10 more , Hayes-Larson E, Fong JO, Chen R, Posis AIB, Whitmer RA, Gilsanz P, Glymour MM, Torres JM, Kotwal AA, Mayeda ER
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41589522 · Full text
BACKGROUND: Social isolation is a key social determinant of health, yet research on its relationship with functional impairment is limited. We compared functional impairment score trajectories of older adults who experie...
BACKGROUND: Social isolation is a key social determinant of health, yet research on its relationship with functional impairment is limited. We compared functional impairment score trajectories of older adults who experienced social isolation versus those who did not, using 2 different statistical approaches to handle attrition due to dropout and death. METHODS: Data were from 2 Northern California observational cohorts of people aged 50+ (n = 2476): Kaiser Healthy Aging and Different Life Experiences (KHANDLE) and Study of Healthy Aging in African Americans (STAR). We fit linear mixed effects models for functional impairment scores (sum of 12 items measuring basic activities of daily living [ADLs], instrumental ADLs, and mobility; range: 0-36) by baseline social isolation status (yes/no; 3-5 positive answers on 5 social contact items), adjusted for age and sex/gender. We estimated average marginal wave-specific differences in functional impairment scores, comparing approaches to address attrition. RESULTS: At baseline, 30% of participants reported social isolation; the median functional impairment score was 2 (Q1, Q3 = 0, 5). Baseline functional impairment scores were 1.03 points (95% CI, 0.84-1.20) higher among participants experiencing social isolation versus not. At wave 4, this difference decreased to 0.80 (95% CI, 0.52-1.07) among those remaining in the study and increased to 1.16 (95% CI, 0.83-1.42) assuming attrition was eliminated. Dropout and death were higher among participants experiencing social isolation. CONCLUSION: In a diverse cohort of older adults, those experiencing social isolation tend to experience greater functional impairment, but differences in trajectories depend on how attrition is handled.
Sleep, metabolites, and global cognition: a mediation analysis of plasma metabolic profiles in the West China Health and Aging Cohort.
Wu X, Zhao Q, Zhang X … +13 more , Yan H, Dui X, Jiang K, Chen X, Lin L, Ma T, Zhao X, Xiao J, Zhang T, Long L, Liao J, Jiang X, Li J
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41581209 · Publisher ↗
BACKGROUND: Growing evidence connects sleep disorders with cognitive impairment in older adults, though underlying biological mechanisms remain unclear. We investigated how plasma metabolic profiles mediate the relations...
BACKGROUND: Growing 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 cognitive function. METHODS: In a cross-sectional analysis of 3888 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. RESULTS: We identified 93 metabolites associated with sleep characteristics and 26 linked to cognitive outcomes. Four individual metabolites, including 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. CONCLUSIONS: Plasma 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.
Preoperative plasma glial fibrillary acidic protein and postoperative delirium in older adults.
Liu J, Arnold SE, Kivisäkk P … +11 more , Fatima H, Schmitt EM, Marcantonio ER, Pascual-Leone A, Shafi MM, Cavallari M, Jones RN, Ngo LH, Inouye SK, Vasunilashorn SM, Fong TG
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41581135 · Full text
BACKGROUND: Delirium 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 protei...
BACKGROUND: Delirium 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. METHODS: Data were obtained from the ongoing prospective successful aging after elective surgery (SAGES) study. GFAP was measured in preoperative plasma (n = 529). Postoperative 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. RESULTS: Overall 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 (fourth vs. first 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). CONCLUSIONS: High 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.
Calcium chloride supplementation promotes longevity in Caenorhabditis elegans via a CKK-1 and CMK-1-dependent UNC-43/DAF-16 signaling mechanism.
Chin CH, Yang NC
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41581129 · Publisher ↗
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-depend...
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 Caenorhabditis 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.
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