Aug 2026· Experimental Gerontology· Vol 224, pp.
113290
· 0 citations
Medicine
TL;DR
Peripheral blood mtDNA-CN is independently associated with cardiac diastolic function in hospitalized older adults, with a more pronounced association in frail individuals.
Abstract
Background
Frailty is a common geriatric syndrome associated with impaired mitochondrial biology and increased cardiovascular vulnerability in older adults. Mitochondrial DNA copy number (mtDNA-CN) is an indirect proxy of mitochondrial genome abundance, and has been linked to cardiovascular disease risk; its relationship with cardiac diastolic function in frail older patients remains unclear. This study examined the association between peripheral blood mtDNA-CN and echocardiographic diastolic function indices, and whether frailty status modifies this relationship.
Methods
We recruited 576 hospitalized older adults (aged ≥60 years) at Jiangsu Province Hospital between October 2020 and August 2022; 187 participants met all criteria. Frailty was assessed with the Physical Frailty Phenotype (PFP) scale (non-frail n = 52, pre-frail n = 77, frail n = 58). Diastolic function was evaluated by the E/A ratio, E/e', septal e' and lateral e' velocities, with left ventricular mass index (LVMI) additionally reported. mtDNA-CN was quantified by quantitative real-time PCR (qPCR). Multivariable models were adjusted for age, sex, BMI, systolic blood pressure, heart rate, HbA1c, eGFR, coronary artery disease, neutrophil percentage and platelet count; a progressive-adjustment sensitivity analysis of 11 nested models further added C-reactive protein (CRP), the complete leukocyte differential, hemoglobin, the Geriatric Nutritional Risk Index (GNRI) and physical activity level. Diagnostic models were internally validated by bootstrap optimism correction (1000 resamples) and repeated stratified 10-fold cross-validation.
Results
mtDNA-CN decreased significantly with increasing frailty severity (P < 0.001) and was positively correlated with the E/A ratio (r = 0.494, P < 0.001), lateral e' (r = 0.479, P < 0.001) and septal e' (r = 0.291, P < 0.01), but not with E/e' (r = -0.100, P = 0.172), LVMI (r = 0.037, P = 0.611), or any structural or systolic index. In the fully adjusted models, log(mtDNA-CN) remained independently associated with the E/A ratio (β = 0.50, 95% CI 0.37-0.63), lateral e' (β = 0.44, 95% CI 0.32-0.57) and septal e' (β = 0.21, 95% CI 0.05-0.37), and the estimate was stable across all 11 progressively adjusted models. Associations were consistent across sex, diabetes, hypertension, coronary artery disease and age >80 years. Frailty status significantly amplified the association between mtDNA-CN and diastolic function (all interaction P < 0.05). Optimism-corrected AUCs for mtDNA-CN alone were 0.79, 0.81 and 0.72 for E/A, lateral e' and septal e', exceeding an age-plus-grip-strength model (0.61, 0.68, 0.63); an integrated model reached 0.79, 0.83 and 0.73.
Conclusion
Peripheral blood mtDNA-CN is independently associated with cardiac diastolic function in hospitalized older adults, with a more pronounced association in frail individuals. mtDNA-CN mtDNA-CN may represent a potential non-invasive marker for the early detection of diastolic impairment and may facilitate cardiovascular risk stratification in frail older adults.
Frailty, defined as increased vulnerability to stressors and impaired recovery of homeostasis, poses a major health challenge among older and multimorbid adults. Frailty is also observed in middle-aged and disease-free adults, though evidence remains scarce. Understanding the physiological characteristics of frail individuals free of chronic diseases may inform about the underlying mechanisms of frailty and its clinical management. We assessed frailty in a large disease-free middle-aged cohort and examined the associations of markers of physiological function with frailty. We analyzed data from 117,163 middle-aged adults (mean age 53.9 ± 8.0 years) free of known chronic conditions from the UK Biobank. Associations between frailty status (robust, prefrail, frail; defined using the Fried Frailty Phenotype) and 29 physiological markers were examined using multinomial logistic regression adjusted for sociodemographic and lifestyle factors. Overall, 1,293 (1.1%) participants were frail and 38,401 (32.8%) prefrail. Anthropometric measures (body fat % waist-to-hip ratio), triglycerides, some markers of hepatic (gamma-glutamyl transferase, alkaline phosphatase) and renal function (cystatin C), glucose metabolism (HbA1c), inflammation (hsCRP), and white blood cell count including leukocyte and neutrophil count and the neutrophil-to-lymphocyte ratio were directly associated with frailty. In contrast, blood pressure, lung function markers (FEV1, FVC), other hepatic (aspartate aminotransferase, bilirubin) and renal markers (creatinine and creatinine-to-cystatin C ratio), and the endocrine marker IGF-1 were inversely associated with frailty. Associations were generally similar but weaker for prefrailty. Frailty in disease-free middle-aged adults was associated with multisystem physiological alterations resembling those observed in older and multimorbid populations, suggesting early physiological dysregulation preceding clinically manifest chronic disease.
P. Stürmer, Gabriella C. Silva, A. Fayosse et al.· GeroScience· 0 citations
Background
Frailty predicts mortality in older adults with heart failure, but its association with recurrent hospitalization, and its value relative to left ventricular ejection fraction (LVEF), remain poorly characterized in Asian populations.
Methods
We followed 150 consecutive Vietnamese outpatients aged 60 years or older with chronic heart failure for 12 months for recurrent all-cause hospitalization. Frailty was defined as a Clinical Frailty Scale (CFS) score of 5 or higher. The primary analysis used the Andersen-Gill recurrent-event model; a four-level frailty-comorbidity composite was derived from the Charlson Comorbidity Index, and discrimination was compared by Harrell's C-statistic.
Results
Of 150 participants (median age 75 years; 59.3% male), 54 (36.0%) were frail and 79 (52.7%) were hospitalized at least once. Frailty was associated with recurrent hospitalization after adjustment for age and sex (adjusted HR 1.73, 95% CI 1.06-2.83; p = 0.028). The frailty-comorbidity composite showed a graded increase in hospitalization burden that did not persist after adjustment. Discrimination was modest across all models (C-statistics near 0.60) and did not differ significantly between frailty (0.581) and LVEF (0.568); combining both gave 0.610 (95% CI 0.560-0.661).
Conclusion
In older Vietnamese adults with chronic heart failure, frailty was associated with recurrent all-cause hospitalization after adjustment for age and sex, with modest discrimination similar to LVEF-based stratification. Baseline frailty assessment may help identify higher-risk patients and warrants prospective evaluation.
H. Nguyen, T. C. Trinh· Annals of Geriatric Medicine...· 0 citations
Background: Recent clinical investigations have drawn attention to cognitive frailty as a composite syndrome that occurs with increasing frequency in populations affected by chronic metabolic disorders, most notably type 2 diabetes mellitus. Despite this recognition, empirical data characterizing its prevalence and predisposing determinants among younger, community-dwelling adults with diabetes remain insufficient.
Objective: The aim of this investigation was to determine whether sarcopenia independently contributes to the occurrence of cognitive frailty in adults with diabetes managed within the primary care system.
Methods: Adopting a cross-sectional design, the study recruited 281 adults living with diabetes from two community-based health facilities. The Mini-Mental State Examination (MMSE) served as the primary cognitive assessment tool, and the SARC-F questionnaire—a validated self-report screening instrument rather than a direct physiological measure of muscle mass or handgrip strength—was used to assess sarcopenia risk. Chi-square analysis tested bivariate associations, and adjusted prevalence ratios (PRs) were computed using modified Poisson regression with robust variance, an approach suited for cross-sectional data in which outcomes are not rare.
Results: The overall prevalence of cognitive frailty in the study cohort was 3.2%. In multivariate models, sarcopenia was associated with a significantly higher likelihood of cognitive frailty (adjusted PR = 6.84; 95% CI: 1.55–30.19).
Conclusion: Sarcopenia is a clinically meaningful, independent risk factor for cognitive frailty in community-dwelling adults with diabetes. Integrating parallel assessments of sarcopenia and cognitive function into routine primary care diabetes management may improve early detection and help reduce downstream adverse health outcomes.
Laurentius Johan Ardian, F. Wardhani, Bisarda Kanira et al.· Glosains Jurnal Sains Global...· 0 citations
BACKGROUND AND OBJECTIVES
The association between frailty and kidney function remains poorly investigated. We aimed to evaluate the associations between frailty status and kidney function (rapid kidney function decline and progressed to CKD in middle-aged and older Chinese population.
METHODS
A total of 3,112 participants with eGFRcr-cys ≥60 ml/min per 1.73 m2 and aged more than 60 years from the China Health and Retirement Longitudinal Study were included in analyses. Frailty was assessed using the Frailty Phenotype, which included assessments of unintentional weakness, slowness, exhaustion, low activity, and shrinking.
RESULTS
During the 4 years of follow-up, 499 (16.03%) participants experienced kidney function decline and 118 (3.79%) participants progressed to CKD. After multivariable adjustment of baseline eGFRcr-cys level and other risk factors, each 1-unit higher in frailty score was associated with 17% increased risk for the rapid decline in kidney function (annualized decline in eGFRcr-cys ≥ 3 ml/min per 1.73 m2). In addition, frailty was associated with an increased risk of rapid decline in kidney function (odds ratio=1.17, 95% confidence interval:1.04-1.30). Individuals with slowness or exhaustion alone also had increased risk of rapid decline in kidney function.
CONCLUSION
Frailty was associated with increased risk of rapid decline in kidney function among Chinese adults with normal kidney function.
Frailty is a common geriatric syndrome linked to disability and mortality. Respiratory sarcopenia (RS), recently conceptualized as concurrent decline in muscle and respiratory function, may contribute to frailty, but evidence is scarce. We analyzed data from the nationally representative China Health and Retirement Longitudinal Study. Probable RS was defined, following the 2023 consensus, as low peak expiratory flow rate (PEFR) plus low appendicular skeletal muscle (ASM) mass. Frailty was assessed using the Fried frailty phenotype. Cross-sectional associations were assessed using logistic regression among 2107 adults aged ≥60 years in 2011; incident frailty was assessed using Cox proportional hazards models among 1599 participants followed through 2015. In 2011, the frailty prevalence was 8.4%, and probable RS affected 28.0%. Cross-sectionally, low ASM mass (odds ratio [OR] = 2.17; 95% confidence interval [CI] = 1.55–3.05; P < .001), low PEFR (OR = 2.23; 95% CI = 1.31–3.79; P = .003), and probable RS (OR = 2.53; 95% CI = 1.81–3.52; P < .001) were all linked to frailty. Over 5746 person-years, the frailty incidence was 13.9 per 1000 person-years. Probable RS predicted incident frailty (hazard ratio [HR] = 3.26; 95% CI = 2.08–5.10; P < .001), as did low ASM mass (HR = 3.78; 95% CI = 2.37–6.04; P < .001), whereas low PEFR alone (HR = 1.47; 95% CI = 0.77–2.79; P = .243) was not statistically significant. Probable RS was associated with incident frailty in Chinese older adults. Its reliance on simple, low-cost measures highlights potential utility for early risk stratification, and interventions addressing both muscle and respiratory function may help delay frailty progression.
Background Geriatric syndromes (GS) are highly prevalent among community-dwelling older adults with self-reported physician-diagnosed coronary heart disease (CHD), but their association with intrinsic capacity (IC) remains poorly characterized. Methods We analyzed cross-sectional data from 5,835 community-dwelling Chinese older adults with self-reported physician-diagnosed CHD (mean age 74.4 years; 65.8% women). GS burden (0 to ≥4) and specific comorbidities were examined against overall IC impairment and its five domains (locomotion, cognition, sensory, vitality, psychological). Adjusted prevalence ratios (PR) were estimated using multivariable modified Poisson regression models. Sensitivity analyses accounted for frailty, disability, and conceptual overlap between exposure and outcome domains, and the exclusion of severe end-stage deficits. Results Overall, 69.6% of participants had ≥1 GS. IC impairment prevalence increased progressively with GS burden, from 35.6% (0 GS) to 84.7% (≥4 GS). Compared to those with 0 GS, participants with ≥4 GS had a substantially higher prevalence of overall IC impairment (PR = 2.00; 95% CI: 1.76–2.27), locomotion difficulties (PR = 6.52), and psychological problems (PR = 6.68; all p < 0.001). Individually, delirium symptoms showed the strongest association with cognitive (PR = 4.09) and overall IC impairment (PR = 1.48). Specific dyadic GS combinations (e.g., anxiety paired with chronic constipation) remained independently associated with IC impairment even after adjusting for the total concurrent GS burden. Sensitivity analyses confirmed that cumulative GS associations remained stable after adjusting for physical vulnerability (≥4 GS PR = 1.73) and excluding severe deficits. No significant interactions were observed by age, sex, or region. Conclusion In community-dwelling older adults with self-reported physician-diagnosed CHD, a higher GS burden is strongly and independently associated with IC impairment, reflecting a functional continuum from early capacity declines to advanced physical vulnerability. This graded relationship persists even when accounting for physical vulnerability, highlighting the critical value of identifying high-risk GS clusters to proactively manage IC.
Jiaojiao Qiu, Shuaishuai Zhang, Yue Chen et al.· Frontiers in Public Health· 0 citations
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