The Journals Of Gerontology. Series A, Biological Sciences And Medical Sciences[JOURNAL]
Sun
200 papers
Sex-specific proteostasis and urothelial responses to senolytic therapy in the aged mouse bladder.
Kasturi S, Salazar AM, Hardy CC … +2 more , Korstanje R, Mysorekar IU
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41741369 · Full text
Lower urinary tract dysfunction (LUTD) increases with age and disproportionately affects women, yet the molecular mechanisms underlying this sex bias remain poorly defined. The aging bladder plays a central role in this...
Lower urinary tract dysfunction (LUTD) increases with age and disproportionately affects women, yet the molecular mechanisms underlying this sex bias remain poorly defined. The aging bladder plays a central role in this decline, and our previous work identified increased cellular senescence, oxidative stress, and activation of the PERK arm of the unfolded protein response (UPR) as key features of bladder aging. In this study, conducted as part of the NIH Common Fund SenNet program to investigate cellular senescence in mice, we explored the therapeutic potential of a senolytic drug combination of Dasatinib and Quercetin (D&Q) in male and female aged (25-month-old) bladders from genetically diverse Diversity Outbred mice. We first assessed sex differences in aged bladders (>20 months of age), then evaluated whether D&Q treatment could improve bladder health by modulating ER stress. We identified significant baseline sex differences in UPR and ER-associated degradation (ERAD) proteins, with higher expression of PERK pathway ER stress components in females and more efficient ERAD and autophagy flux in males. While D&Q did not broadly alter ER stress or autophagy markers, it selectively increased ERAD markers in females. D&Q also enhanced uroplakin expression and urothelial thickness in aged females, suggesting potential benefit to urothelial integrity. These findings suggest a potential sex-specific regulatory mechanism within the UPR pathway that may contribute to the increased vulnerability of aged females to bladder dysfunction.
Can infections drive frailty? Insights from the Baltimore Longitudinal Study of Aging.
Ragusa FS, Tanaka T, Duggan MR … +5 more , Walker KA, Veronese N, Dominguez LJ, Barbagallo M, Ferrucci L
J Gerontol A Biol Sci Med Sci · 2026 Apr · PMID 41741350 · Publisher ↗
BACKGROUND: Frail older people have elevated risk of developing infection. Whether a history of infections is associated with frailty and mortality has not been fully explored. This study investigates the associations be...
BACKGROUND: Frail older people have elevated risk of developing infection. Whether a history of infections is associated with frailty and mortality has not been fully explored. This study investigates the associations between infection history, frailty and their coexistence on all-cause mortality. METHODS: Study used 1399 participants (mean age 65.3 years; 51.5% females) of the Baltimore Longitudinal Study of Aging where infection history was established by ICD-9 codes. Frailty was assessed using a 44-item Frailty Index (FI). The association between infection history and frailty was explored using multiple linear regression. Their association with mortality was assessed using Cox proportional hazard models. RESULTS: A history of any infections, and specific infections, including urinary tract, viral infection, pneumonia, and Herpes virus were associated with higher FI (p ≤ .01). Plasma leptin and BMI were positive mediators of the association between infection history and frailty. There was a significant association between infection history and FI progression (from FI < 0.12 to FI ≥ 0.12) in participants 65 years and older (HR: 1.43, 95% CI, 1.08-1.90, p = .02). Participants with both infections' history and high FI (FI ≥ 0.12) had higher risk of mortality (HR = 1.12; 95% CI, 1.05-2.10; p = .02) compared to those without history of infection and low FI. CONCLUSIONS: : A history of infections may accelerate the rate of frailty progression, defined as the transition from robustness to pre-frailty/frailty, and has an independent effect with frailty on increasing the risk of death. The mediating role of leptin suggests that obesity may be implicated in the relationship between history of infections and frailty.
Rethinking immune studies: population-level immune variations and the path forward.
Hysong MR, Memili A, Delaney JA … +10 more , Ekunwe L, Huber S, Reiner AP, Patsy BM, Sitlani CM, Tracy RP, Taylor KD, Olson NC, Doyle MF, Raffield LM
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41741349 · Full text
Shifts in immune cell proportions underlie disease progression and immunotherapy response, positioning them as promising diagnostic biomarkers and therapeutic targets. However, these shifts also occur naturally across th...
Shifts in immune cell proportions underlie disease progression and immunotherapy response, positioning them as promising diagnostic biomarkers and therapeutic targets. However, these shifts also occur naturally across the lifespan and vary with demographic factors such as age and sex, which may complicate their interpretation and clinical utility. While demographic associations have been explored previously, there have been mixed results likely due to small sample sizes and cross-cohort population-specific differences. To address these limitations, we conducted a meta-analysis across 3 large, diverse cohort studies to evaluate associations between 20 immune cell subtypes, 3 informative cell ratios, and a range of sociodemographic variables such as age, sex, self-identified race and ethnicity (SIRE), and socioeconomic status. We find consistent and significant associations across all sociodemographic dimensions. Cytomegalovirus (CMV)-a key driver of immune senescence-emerged as a major contributor to variation in immune composition and CMV antibody levels were higher among women, individuals of lower socioeconomic status, and marginalized racial and ethnic groups. In addition, male sex showed similar patterns of association with immune profiles as aging, whereas race did not. These findings underscore the need to account for diverse sociodemographic factors in immunology study design and participant recruitment to avoid population-specific biases and ensure broadly generalizable results.
Oxidative stress biomarkers as predictors of aging and age-related diseases.
Kumar Y, Pant A, Yadav S … +1 more , Maurya PK
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41729905 · Publisher ↗
Oxidative stress (OS) is a major feature of aging and is first brought on when the generation of Reactive oxygen species (ROS) surpasses the capacity of antioxidant defenses to neutralize them. Long-term exposure to ROS...
Oxidative stress (OS) is a major feature of aging and is first brought on when the generation of Reactive oxygen species (ROS) surpasses the capacity of antioxidant defenses to neutralize them. Long-term exposure to ROS gradually damages vital biomolecules, resulting in the development of measurable biomarkers that indicate the degree of OS. Some forms of protein oxidation that impair enzymatic activity and interfere with cellular signaling are carbonyl compounds and advanced oxidation protein products. DNA is susceptible to OS, which can cause lesions like 8-hydroxy-2-deoxyguanosine, which indicates genomic instability and leads to cellular senescence and reduced function. Increased levels of lipid peroxidation byproducts, such as Malondialdehyde, 4-hydroxynonenal, and isoprostanes, indicate disturbed cellular balance and compromised membrane integrity. Additional information about the redox state can be found in antioxidant defenses. While important enzymatic antioxidants like glutathione peroxidase, catalase, and superoxide dismutase frequently show altered activity as one ages, indicating a reduced ability to counteract ROS, non-enzymatic antioxidants like glutathione, vitamins C and E, uric acid, bilirubin, and beta carotene provide extra defense but diminish with age. Combined, these biomarkers show how oxidative damage accumulates gradually and how the body's cellular defenses progressively deteriorate. By mapping their trajectories, we can better understand the biology of aging and develop targeted interventions and early detection tools to promote healthy aging. In this review, we summarized various OS biomarkers that help in the prediction of aging and age-related diseases.
Associations and interaction effects of socioeconomic, lifestyle, and genetic factors on intrinsic capacity.
Beyene MB, Visvanathan R, Alemu R … +5 more , Theou O, Benyamin B, Cesari M, Beard J, Amare AT
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41729893 · Full text
Intrinsic capacity (IC), which reflects the combined physical and mental reserve of an individual, is a key indicator of healthy aging. While genetic and environmental factors influence IC, the interaction effects betwee...
Intrinsic capacity (IC), which reflects the combined physical and mental reserve of an individual, is a key indicator of healthy aging. While genetic and environmental factors influence IC, the interaction effects between them remain poorly understood. This study investigated the independent and interaction effects of polygenic scores for IC (PGS-IC), socioeconomic status, and lifestyle factors on IC. Baseline data from the Canadian Longitudinal Study on Aging (CLSA; N = 13 112) were analyzed. Associations with IC (outcome) and interaction effects of PGS-IC and socioeconomic factors or lifestyle measures - including composite physical activity and diet scores - were examined using linear regression models. All models were adjusted for age and sex and, additionally, for 5 genetic principal components in models involving PGS-IC. Higher IC was associated with higher education, income, physical activity, and healthier diet patterns. Lower IC was observed among previous and current smokers and those with short (<7 h) or long (>9 h) sleep durations. PGS-IC was positively associated with the IC score. Significant gene-environment interactions were identified between PGS-IC and Mediterranean diet (β = -.003, 95% CI, -0.006, -0.0002), education in younger adults (β = -.109, 95% CI, -0.211, -0.007), and sleep duration (younger adults: long sleep, β = .198, 95% CI, 0.023-0.373; older adults: short sleep, β = -.095, 95% CI, -0.153, -0.036). This study provides preliminary evidence of gene-environment interactions influencing IC, with implications for future research to determine how genetic and modifiable factors can inform strategies for maintaining IC and promoting healthy aging.
Plasma metabolomic profiling and functional disability in older adults.
Pombo-Jiménez A, González-Beltrán D, Yévenes-Briones H … +4 more , Banegas JR, Rodríguez-Artalejo F, Lopez-Garcia E, Caballero FF
J Gerontol A Biol Sci Med Sci · 2026 Apr · PMID 41723833 · Publisher ↗
BACKGROUND: Functional disability is a major public health concern in older adults, predicting adverse outcomes such as hospitalization, institutionalization, and mortality. While previous studies have linked metabolomic...
BACKGROUND: Functional disability is a major public health concern in older adults, predicting adverse outcomes such as hospitalization, institutionalization, and mortality. While previous studies have linked metabolomic profiles to aging-related conditions, their relationship with functional disability remains unclear. METHODS: This study examined associations between plasma metabolomic profiles and functional disability in 1450 community-dwelling adults aged ≥65 years from the Seniors-ENRICA 2 cohort. Disability was assessed using the Katz Index for activities of daily living (ADL disability) and the Lawton-Brody Scale for instrumental activities of daily living (IADL disability). Twenty-seven metabolites quantified by high-throughput nuclear magnetic resonance spectroscopy were included in the analyses. Firth logistic regression estimated cross-sectional and 5-year longitudinal associations, adjusting for sociodemographic and lifestyle factors. RESULTS: Higher concentrations of tyrosine (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.61-0.98), pyruvate (0.69; 0.50-0.95), and lactate (0.78; 0.61-0.98) were cross-sectionally associated with lower odds of ADL disability, whereas glycine (1.31; 1.05-1.64) and Glycoprotein A (GlycA) (1.47; 1.17-1.86) were linked to greater odds. After 5 years, higher lactate (1.17; 1.00-1.37) was associated with increased ADL disability, whereas creatinine predicted lower odds of ADL (0.80; 0.65-0.97) and IADL disability (0.68; 0.47-0.98). In incident disability analyses, higher creatinine (0.76; 0.62-0.94) and citrate (0.79; 0.66-0.94) concentrations predicted lower odds of ADL disability, while GlycA (1.36; 1.01-1.84) remained associated with higher odds of IADL disability. CONCLUSIONS: These findings suggest that several plasma metabolites may serve as early biomarkers of functional decline and inform prevention strategies in older adults.
Leveraging precision medicine analytics to optimize inflammation reduction and enhance physical function in older adults.
Tharwani SD, Lynch DH, Boccaccio DE … +6 more , Spangler H, Gao D, Nelson AE, Zeng D, Batchek D, Batsis JA
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41719202 · Publisher ↗
BACKGROUND: Chronic inflammation in older adults is a key contributor to functional decline and mortality. Although anti-inflammatory medications have shown limited success in improving physical function, emerging target...
BACKGROUND: Chronic inflammation in older adults is a key contributor to functional decline and mortality. Although anti-inflammatory medications have shown limited success in improving physical function, emerging targeted approaches offer new promise. We applied machine learning to identify clusters of older adults with shared patterns of inflammatory and cardiometabolic dysregulation and evaluated their responses to specific interventions. METHODS: We conducted a secondary analysis of the Enabling Reduction of low-grade Inflammation in Seniors (ENRGISE) multicenter, double-blind, placebo-controlled, factorial trial. This trial assessed the effects of losartan, omega-3, combination therapy, or placebo on interleukin-6 (IL-6) levels and 400-m walking speed. Key variables were selected using least absolute shrinkage and selection operator (LASSO), followed by linear regression to identify those significantly affecting the outcome slope. The optimal intervention was defined as the one that maximized the estimated slope improvement. RESULTS: We included 287 participants (47.4% female; mean age 77.6 ± 5.4 years) with a baseline IL-6 of 4.81 pg/mL. If all participants had received the recommended interventions, the estimated mean IL-6 slope would be -0.70 pg/mL/year (95% CI, -3.71, 1.41), compared to -0.51 pg/mL/year (-1.47, 0.35) among those randomized. The estimated improvement in walking speed was +0.0017 m/s/year (-0.0336, 0.0407) for the recommended interventions versus +0.0015 m/s/year (-0.0145, 0.0154) observed in the trial. For grip strength, the slope was -1.02 kg/year (-2.63, 0.57) for the recommended group and -1.02 kg/year (-1.79, -0.45) for the trial group. CONCLUSION: Although results were not significant, our findings suggest that tailored interventions based on individuals' unique profiles may yield more favorable effects compared to non-tailored approaches. However, further powered studies should continue to explore precision medicine analytics and their potential to help identify more effective and personalized interventions.
Avoiding trip- and slip-hazards in suburban footpaths by older adults: an immersive virtual reality experiment.
He Y, Kim J, Brodie MA … +2 more , Lord SR, Okubo Y
J Gerontol A Biol Sci Med Sci · 2026 May · PMID 41706639 · Publisher ↗
BACKGROUND: Older people often fall due to trips and slips in daily life. This study aimed to elucidate the mechanisms of trip- and slip-hazard avoidance while walking through an immersive virtual reality suburban footpa...
BACKGROUND: Older people often fall due to trips and slips in daily life. This study aimed to elucidate the mechanisms of trip- and slip-hazard avoidance while walking through an immersive virtual reality suburban footpath. METHODS: Forty-six participants (71.8 ± 4.7 [65-84] years) wore an immersive head-mounted display (Oculus Rift S) and safety harness while walking on a split-belt treadmill (M-Gait). Participants walked on a virtual footpath while avoiding hazards including raised concrete slabs (trips) and puddles (slips) and as a secondary task collected apples. Foot-hazard contacts resulted in treadmill belt accelerations/decelerations to evoke balance loss. Hazard contact rates and gait kinematics were measured using Vicon motion capture. RESULTS: Participants contacted more trip-hazards (63.1%) than slip-hazards (22.2%; p <.001). Trip-hazards were more frequently collided with by the trailing foot (56.9%) compared to the leading foot (16.7%; p <.001). Trailing foot contact with both trip- and slip-hazards resulted in significant changes in extrapolated Centre of Mass (XCoM) and Margin of Stability (MoS) (p <.05). Following trailing foot contacting trip-hazards, participants compensated effectively by increasing MoS, whereas contacting slip-hazards reduced MoS, indicating a higher risk of losing balance. CONCLUSION: On a virtual suburban footpath, older adults often collided with trip-hazards with their trailing foot, which was typically beyond their visual field, while slip-hazards more commonly involved the leading foot. These insights can support the development of fall prevention programs that better mirror everyday walking challenges.
Extracellular vesicle-derived mitochondrial genes as potential biomarkers for brain aging in human.
Yu Q, Yu S, Chen H … +7 more , Cui Z, Cheng Q, Jin Y, Zong S, Wang Y, Li M, Lu Z
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41701160 · Publisher ↗
Aging significantly impacts brain function, and identifying reliable biomarkers for early detection of age-related neurodegeneration is crucial for improving diagnosis and treatment outcomes. This proof-of-principle stud...
Aging significantly impacts brain function, and identifying reliable biomarkers for early detection of age-related neurodegeneration is crucial for improving diagnosis and treatment outcomes. This proof-of-principle study aims to evaluate the abundance of mitochondrial DNA (mtDNA) targets within plasma-derived extracellular vesicles (EVs) and to investigate whether they correlate with established biomarkers of brain aging, independent of chronological age and renal function. mtDNA copy number was quantified using absolute quantitative polymerase chain reaction (qPCR). Brain aging biomarkers were measured by enzyme-linked immunosorbent assay (ELISA). Multivariable regression analysis was performed to examine the associations between EV mitochondrial genes and aging biomarkers. A multi-biomarker model was developed to assess the performance of combined biomarkers in distinguishing between age groups. We observed that EV mitochondrial gene levels were significantly increased with age (p < .001). Levels of neurofilament light chain (NfL), amyloid-beta (Aβ42 and Aβ40), also showed significant age-related increases (p < .001). A multi-biomarker model combining EV mitochondrial genes and brain aging biomarkers showed the optimal performance in distinguishing older adults from younger individuals, with an area under the receiver operating characteristic (ROC) curve (AUC) significantly higher than that of any single biomarker (p < .01). These findings collectively indicate that EV-derived mitochondrial genes, in combination with other biomarkers like NfL, hold great potential as a noninvasive tool for early detection and monitoring of brain aging and neurodegenerative diseases.
Early life adversity, educational attainment, and cardiometabolic risk among middle-aged and older adults in the United States.
García C, Xu Y, Parella MA
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41701154 · Full text
BACKGROUND: Early life adversity (ELA) is a known contributor to physiological dysregulation and chronic disease in adulthood. However, less is known about how specific ELA domains influence cardiometabolic dysregulation...
BACKGROUND: Early life adversity (ELA) is a known contributor to physiological dysregulation and chronic disease in adulthood. However, less is known about how specific ELA domains influence cardiometabolic dysregulation later in life, or whether these associations vary by race/ethnicity and educational attainment. METHODS: We used nationally representative data from the 2006-2016 Health and Retirement Study (n = 19 747 adults aged > 50) to estimate generalized linear models assessing associations between 5 ELA domains and cardiometabolic risk scores (cMetS). Models were stratified by race/ethnicity (foreign-born Latino, US-born Latino, non-Latino Black, non-Latino White) and adjusted for demographic, lifestyle, medication, and socioeconomic covariates. Interaction terms tested whether educational attainment moderated these associations. RESULTS: Childhood socioeconomic disadvantage was associated with higher cMetS in the full sample and among foreign-born Latino and non-Latino White adults, but not among US-born Latino or non-Latino Black adults. Among individuals exposed to early adversity, educational attainment was associated with lower cMetS, although educational gradients varied by race/ethnicity. Non-Latino White adults demonstrated consistent educational protection across all adversity domains. Non-Latino Black adults showed educational buffering limited to childhood socioeconomic disadvantage and disruptive home environments. Among foreign-born Latinos, educational gradients were observed specifically for childhood socioeconomic disadvantage. US-born Latinos showed no statistically significant educational buffering. CONCLUSIONS: Early socioeconomic disadvantage has enduring effects on cardiometabolic health, and education can buffer these effects. However, education's protective capacity varies across populations. Addressing life course adversity in aging populations requires attention to both early disadvantage and social contexts that determine who can translate educational achievements into health benefits.
The influence of multiple air pollutants on sarcopenia progression: a multi-state analysis in a prospective cohort.
Sang N, Dai X, Yang Q … +9 more , Nie M, He W, Wang Z, Liu H, Duan Y, Liu Q, Han L, Wu G, Cheng L
J Gerontol A Biol Sci Med Sci · 2026 May · PMID 41701152 · Publisher ↗
BACKGROUND: Air pollution's influence on sarcopenia progression remains insufficiently studied. METHODS: Using the UK Biobank cohort, we included 50381 participants initially free of probable sarcopenia and sarcopenia. E...
BACKGROUND: Air pollution's influence on sarcopenia progression remains insufficiently studied. METHODS: Using the UK Biobank cohort, we included 50381 participants initially free of probable sarcopenia and sarcopenia. Exposures to PM2.5, PM10, PM2.5-10, NO2, and NOx for each transition stage were estimated at each participant's residential addresses using data from the UK's department. Parametric g-computation was applied to estimate cumulative risks under hypothetical pollution reduction scenarios. Multistate models were used to examine associations between air pollution and sarcopenia progression. RESULTS: During 8.98 years (median), 4445 (8.8%) participants developed probable sarcopenia; 17 (0.4%) progressed to sarcopenia. Parametric g-computation estimated that a simultaneous 10% reduction in all 4 pollutants would decrease the 15-year cumulative risk (risk ratio [RR] = 0.93; risk difference [RD] = -2.21). In multistate models, PM2.5 increased risks of probable sarcopenia (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.02-1.10), sarcopenia (HR: 1.18; 95% CI: 1.04-1.34), baseline to death (HR: 1.11; 95% CI: 1.02-1.20,) and probable sarcopenia to death (HR: 1.24; 95% CI: 1.04-1.50). NO2 showed similar associations: probable sarcopenia (HR: 1.06; 95% CI: 1.02-1.10), sarcopenia (HR: 1.23; 95% CI: 1.09-1.39), baseline to death (HR: 1.10; 95% CI: 1.01-1.19), and probable sarcopenia to death (HR: 1.23; 95% CI: 1.01-1.50). NOx increased risks for probable sarcopenia (HR: 1.06; 95% CI: 1.03-1.09), sarcopenia (HR: 1.15; 95% CI: 1.04-1.26), and probable sarcopenia to death (HR: 1.22; 95% CI: 1.04-1.43). Stratified analyses indicated effect modification by sex, household income, and body mass index (BMI). CONCLUSIONS: These findings highlight the critical role of clean air in preventing and delaying sarcopenia progression, especially in vulnerable populations.
Obesity and healthy aging: fat, muscle, and bone trade-offs in an era of potent weight-loss pharmacotherapy.
Siddiqui S, Tabatabaie V, Aleksic S
J Gerontol A Biol Sci Med Sci · 2026 Feb · PMID 41693033 · Full text
Abstract loading — click title to view on PubMed.
Intrinsic capacity and healthy aging in the United Kingdom and Brazil: a coordinated analysis of 2 population-based cohort studies.
Bertola L, Wu YT, Aliberti MJR … +6 more , Kingston A, Hiratsuka M, Ferriolli E, Prina M, Suemoto CK, Brazil-UK Network on Healthy Aging
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41693015 · Publisher ↗
BACKGROUND: Although intrinsic capacity (IC) is a multidimensional marker of healthy aging, cross-country validation in diverse cultural and socioeconomic contexts remains limited. We study aimed to harmonize the operati...
BACKGROUND: Although intrinsic capacity (IC) is a multidimensional marker of healthy aging, cross-country validation in diverse cultural and socioeconomic contexts remains limited. We study aimed to harmonize the operationalization of IC and examine its associations with sociodemographic characteristics and health outcomes in the United Kingdom and Brazil. METHODS: Nationally representative cohorts of community-dwelling older adults in both countries, aged ≥60 years from the English Longitudinal Study of Ageing (n = 3392) and Brazilian Longitudinal Study of Ageing (n = 3580). IC was derived using bi-factor models comprising locomotor, cognition, psychological, sensory, and vitality measures, standardized to a 0-100 scale. Linear regressions assessed IC associations with sociodemographic factors. Logistic regressions examined IC associations with poor/fair self-rated health and disability in basic activities of daily living (ADL) and instrumental ADL (IADL). We tested whether education and wealth modified these associations. RESULTS: Mean IC scores were lower in women than in men, with differences of 3.06 points (95% confidence interval [CI] = 2.30-3.82) in the United Kingdom and 8.14 (95% CI = 7.40-8.90) in Brazil. Older age, non-White race/ethnicity, less education, and lower wealth were also linked to lower IC scores. Higher IC was associated with lower odds of poor/fair self-rated health in the United Kingdom (odds ratio [OR] = 0.32; 95% CI = 0.29-0.35) and Brazil (OR = 0.54; 95% CI = 0.48-0.61). Higher IC was also linked to lower odds of ADL and IADL disability in both cohorts. No significant interactions were found. CONCLUSIONS: IC showed consistent associations with sociodemographic factors and health outcomes both countries. IC may inform equitable, person-cent red healthy aging policies for older adults in diverse contexts.
Associations of physical frailty with risk of incident cardiovascular disease by mediation of plasma metabolome changes.
Sun G, Yu L, Mahemuti N … +8 more , Sun A, Zhang D, Liu Y, Xi R, Zhang Q, Zhang X, Xing X, Yang X
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41693009 · Publisher ↗
BACKGROUND: Frailty has been increasingly recognized as a significant contributor to adverse cardiovascular outcomes. However, the metabolic mechanisms underlying this relationship remain unclear. This study aimed to ide...
BACKGROUND: Frailty has been increasingly recognized as a significant contributor to adverse cardiovascular outcomes. However, the metabolic mechanisms underlying this relationship remain unclear. This study aimed to identify metabolomic signatures of frailty and their mediating roles in cardiovascular disease (CVD) risk. METHODS: Using data from 95 770 UK Biobank participants, we applied elastic net regularized regression to construct a frailty-related metabolomic signature score comprising 43 plasma metabolites across lipids, amino acids, fatty acids, and energy metabolism. Cox proportional hazards models were used to assess the association between this metabolomic signatures score and incident CVD, coronary heart disease (CHD), and stroke over a median follow-up of 13.81 years. Mediation analysis under a counterfactual framework was conducted to quantify the extent to which the metabolomic signatures mediated the frailty-CVD association. RESULTS: High metabolomic signature scores were significantly associated with increased risks of CVD (hazard ratio [HR] = 1.44; 95% confidence interval [CI]: 1.36-1.53), CHD (HR = 1.50; 95% CI: 1.41-1.61), and stroke (HR = 1.45; 95% CI: 1.37-1.54). Mediation analysis indicated that the metabolomic signature accounted for 14.9% of the association between frailty and overall CVD, 16.0% for CHD, and 16.9% for stroke. Pathway enrichment analysis revealed 7 metabolic pathways significantly enriched in frailty, with the primary associations implicating carbohydrate and amino acid metabolism. CONCLUSIONS: This study highlights a distinct frailty-related metabolic profile that independently predicts cardiovascular risk and partially mediates the frailty-CVD association. These findings underscore the value of metabolomic profiling in guiding early detection and prevention strategies for frailty-related cardiovascular outcomes.
Social and clinical frailty indices in aging mice: a comparative analysis of longitudinal and cross-sectional designs.
Razzoli M, Collinge CW, Luciana M … +1 more , Bartolomucci A
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41692986 · Full text
Aging is a heterogeneous phenomenon provoked by biological processes that still need to be fully understood. Frailty is a relevant outcome of aging reflecting biological decline that can be quantified through indices mea...
Aging is a heterogeneous phenomenon provoked by biological processes that still need to be fully understood. Frailty is a relevant outcome of aging reflecting biological decline that can be quantified through indices measuring the accumulation of functional deficits. Age-related declines may occur across multiple domains of functioning, and longitudinal study designs may better characterize decline within aging individuals. Thus, it is imperative to characterize how frailty indices that capture different functional domains associate with one another over the natural lifespan and across study designs. Here, the clinical frailty index (CFI) and the mouse social frailty index (mSFI) were applied to male and female mice both longitudinally and cross-sectionally over the lifespan. An overall similar association with aging was apparent: within each cohort, both CFI and mSFI were strongly positively associated with age. The utility of the CFI and mSFI as age predictors within the longitudinal study was confirmed. Critically, a model developed within the longitudinal study based on CFI scores, mSFI scores, and sex was able to predict age better than alternative models using only one of the indices. This result suggests that the CFI and the mSFI capture intrinsically different elements of deficit accumulation with age. The same model also showed a good performance in predicting the age of mice in the cross-sectional study. Overall, these results demonstrate that the information captured by both frailty indices is relevant to aging, relationships between indices vary across study design, and both frailty domains are needed to produce better age predictions.
Moving geroscience forward in China: proceedings of the first international exchange forum of the Chinese Geriatrics Society.
Zhang L, Ji T, Bi J … +17 more , Long A, Long YF, Zhang L, Chen N, Ma Y, Chen C, Wang S, Jiang H, Chen Y, Zhou G, Cao F, Hu Y, Ma L, Cheung WH, Kang L, Duque G, Zhang C
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41692982 · Publisher ↗
Held on August 17, 2025 in Guangzhou, the inaugural International Exchange Forum of the Chinese Geriatrics Society marked a significant milestone in advancing geroscience and fostering global collaboration in China. The...
Held on August 17, 2025 in Guangzhou, the inaugural International Exchange Forum of the Chinese Geriatrics Society marked a significant milestone in advancing geroscience and fostering global collaboration in China. The forum brought together leading international experts and emerging Chinese researchers to present the latest advances in aging research. Presentations covered various topics, such as musculoskeletal aging (mitochondrial dysfunction, muscle-bone communication, and exosome-mediated mechanisms in sarcopenia and osteoporosis), cardiovascular aging (tyrosine kinase inhibitor- and anthracycline-induced cardiotoxicity), metabolic regulation (sarcopenic obesity and the gut-muscle axis), neurodegenerative interfaces (androgen-mediated monocyte-microglia interactions in Alzheimer's disease), and geriatric assessment (muscle-specific strength, intrinsic capacity, and gait biomarkers). There was a particular focus on novel mechanistic insights, such as RNA epitranscriptomics, mitochondrial homeostasis, and inter-organ communication, as well as on strategies for early risk prediction, intervention, and personalized management. The forum also emphasized the importance of addressing sex-specific differences and translating basic discoveries into clinical applications. As a platform designed to promote academic dialogue and collaboration, the forum successfully brought together the Chinese and global geroscience communities. It emphasized the necessity of multidisciplinary and international efforts to address the challenges posed by population aging. Moving forward, sustained partnerships, data sharing, and capacity-building initiatives will be essential to accelerating the development of evidence-based, scalable solutions for healthy aging in China and beyond. This event sets a precedent for future exchanges that integrate scientific innovation with clinical practice to improve the health and quality of life of aging populations worldwide.
Associations of common infections with frailty and mortality in two UK cohort studies.
Smeeth D, Warren-Gash C, Green RE … +5 more , Butt J, Waterboer T, Hughes AD, Chaturvedi N, Williams DM
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41692968 · Full text
BACKGROUND: Some common infections are associated with poorer age-related health outcomes; however, findings are limited to a small number of pathogens and frequently inconclusive. This study aimed to expand the range of...
BACKGROUND: Some common infections are associated with poorer age-related health outcomes; however, findings are limited to a small number of pathogens and frequently inconclusive. This study aimed to expand the range of pathogens investigated in relation to frailty and mortality in older age. METHODS: We investigated relationships between seropositivity for 18 viruses, bacteria and protozoa with concurrent frailty and prospective mortality in middle-aged and older adults within two UK population-based cohorts: UK Biobank (N = 9427; aged 40-70 years) and Medical Research Council National Survey of Health and Development (N = 1791; aged 60-65 years). Multiplex serological assays were used to identify seropositivity for each pathogen and frailty was assessed using a frailty index measuring the accumulation of age-related health deficits. Mortality was determined from linked administrative records. RESULTS: Adjusting for sex, age, income and education, previous infection with Toxoplasma gondii ((β = 0.77%; 95% CI, 0.42-1.11) and Helicobacter pylori (0.63%; 95% CI, 0.28-0.97) were associated with higher frailty equivalent to 3.8 or 3.1 years of aging, as was inflammation-weighted pathogen burden (0.41%/SD, 95% CI, 0.25-0.57; 0.42%/SD, 95% CI, 0.26-0.58). Previous infection with Chlamydia trachomatis, human herpes simplex virus 1 and cytomegalovirus were associated with increased frailty after adjustment for sex and age, although relationships were confounded by socioeconomic circumstances. No common infections were robustly associated with mortality. CONCLUSIONS: Our results indicate that infection with H. pylori and T. gondii, and the combined burden of infection may detrimentally impact ageing health. These pathogens may warrant targeting beyond current clinical measures to mitigate the development of frailty.
Revisiting socioeconomic disadvantage estimates in the national health and aging trends study.
Freedman VA, Schrack JA
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41692964 · Full text
Abstract loading — click title to view on PubMed.
Benchmarking weighted estimates of social determinants of Health in the National Health and Aging Trends Study (NHATS).
Gill TM, Leo-Summers L, Liang J … +3 more , Becher RD, Kind AJH, Zang EX
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41692958 · Full text
Abstract loading — click title to view on PubMed.
Bidirectional associations between physical function and physical activity among older adults living with dementia.
Zhu S, Resnick B, Boltz M … +6 more , Galik E, McPherson R, Kuzmik A, Wells C, Lee E, Shim S
J Gerontol A Biol Sci Med Sci · 2026 Mar · PMID 41692954 · Full text
BACKGROUND: Previous research has suggested a likely reciprocal relationship between physical function and physical activity among older adults, but few assessed those living with dementia. This study examined the bidire...
BACKGROUND: Previous research has suggested a likely reciprocal relationship between physical function and physical activity among older adults, but few assessed those living with dementia. This study examined the bidirectional relationship between physical function and physical activity among older adults living with dementia during hospitalization and post discharge periods, and whether the relationship differs by severity of dementia. METHODS: This secondary analysis included 455 older adult patients aged 55 years and older living with dementia from a randomized clinical trial, assessed during admission, discharge, 1-, 6-, and 12-month post-discharge periods. Random intercept cross-lagged panel models (RI-CLPMs) were used to assess the bidirectional relations, controlling for age, comorbidities, admission location, length of stay, discharge location, and intervention status. RESULTS: Average age was 82.47 (SD = 8.49) and majority were female (62.6%) and White (65.3%). The average SLUMS score was 7.51 (SD = 5.90) with 77% (n = 351) having a severe level of cognitive impairment. Antecedent physical function at admission, discharge, and 1-month predicted physical activity at corresponding cross-lagged timepoint separately (range of unstandardized coefficients b's: 0.037-0.043, p's < .05); physical activity at discharge predicted physical function at 1-month (b = 0.708, p = .016). This bi-directional relationship varied by severity of dementia, appearing at the first 2 cross-lagged time points in patients with severe dementia (b's: 0.039-0.049 and 0.464-0.848, all p's < .05), but not in those with moderate dementia. CONCLUSIONS: Physical activity and physical function commonly co-occur among older adults with dementia. Intervention studies promoting both physical function and physical activity among older adults with dementia may achieve greater effectiveness when tailored to differences in dementia severity.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe