Background: The progressive aging of the population represents a critical public health challenge. Within this context, the management of frailty has emerged as a central priority in geriatric care, with Comprehensive Geriatric Assessment (CGA) widely recognized as the gold-standard tool for its evaluation. This study aimed to stratify a large cohort of older adults using a multidimensional approach based on CGA, employing Principal Component Analysis (PCA) and Cluster Analysis to identify distinct phenotypic profiles.
Materials and methods: A cross-sectional study was conducted on 1055 outpatients aged ≥65 years, assessed at the Geriatric Outpatient Service of the University of Cagliari between 2020 and 2024. All participants underwent a CGA. PCA was performed on selected CGA variables, and the resulting components were used for a hierarchical cluster analysis. Post-hoc comparisons between clusters were conducted using ANOVA, Chi-squared or Fisher tests, as appropriate.
Results: PCA identified four principal components explaining 73.5% of total variance. The first component represented a Frailty Axis, while the second reflected Reserve Capacity. Cluster analysis based on these two axes revealed four distinct phenotypes: (I) Vulnerable Low-Complexity (younger patients with low comorbidity but significant cognitive, functional and nutritional impairments), (II) Resilient High-Reserve (low comorbidity with preserved cognitive, functional, and nutritional status and high educational attainment), (III) Resilient Frailty (high comorbidity, functional and nutritional deficits but preserved cognitive reserve) and (IV) Globally Frail (older patients with high comorbidity with multidomain impairments).
Conclusion: These findings demonstrate the ability of CGA, combined with PCA-informed clustering, to identify clinically meaningful frailty and resilience patterns in older adults. The study highlights the role of educational attainment as a key factor contributing to clinical reserve; conversely, it showed that demographic characteristics, laboratory markers, and comorbidities align with frailty.
Cellular senescence is a distinct and definable biological state characterized by irreversible cell cycle arrest, accompanied by the activation of the DNA damage response (DDR), telomere shortening, the senescence-associated secretory phenotype (SASP), and metabolic dysfunction. While senescent cells represent only a small fraction of the total cell population in tissues, they exert a disproportionate and systemic impact on age-related cardiovascular disease (CVD) through paracrine and endocrine mechanisms. This review moves beyond a descriptive list of pathways and instead proposes a unified framework centered on how a small number of senescent cells can reprogram the cardiovascular microenvironment. We focus on the SASP as the central executor of this systemic effect, disseminating local senescence and driving chronic inflammation, fibrosis, and dysfunction across major cardiovascular cell types (cardiomyocytes, endothelial cells, fibroblasts, smooth muscle cells). We integrate key regulatory networks such as mTOR, AMPK, and Sirtuins that modulate the SASP and the senescent state. Furthermore, we discuss the translational promise of senolytics (agents that clear senescent cells) and senomorphics (agents that suppress the SASP) as novel strategies for delaying cardiovascular aging and treating age-related CVD, providing a forward-looking perspective on targeting senescence to promote cardiovascular health. Current research challenges include mechanistic complexity and limitations of animal models and in vitro systems. In the future, it is necessary to combine single-cell sequencing, metabolic intervention, and interdisciplinary technologies to analyze the heterogeneity of cellular aging, and develop early warning and precision treatment strategies based on aging biomarkers, so as to provide new ideas for delaying cardiovascular aging.
Introduction: Cardiometabolic index (CMI) has been highlighted as a useful tool for predicting cardiovascular and metabolic disease, but its association with systemic inflammatory status in the aged population is not yet fully understood. Thus, we investigated the association between the CMI and the triad -metabolic profile X body mass index X inflammaging -in older adults classified as having or not having obesity.
Methods: A total of 132 older adults of both sexes (women-68; men-64, mean age of 71.3±6.5 years), participated in this study. Demographic and anthropometric data, as well as blood samples, were collected to assess blood glucose, lipids, protein, and inflammatory profiles.
Results: Initially, the volunteers were separated according to the CMI values into two groups: G1 (<50% of the mean CMI value) and G2 (>50% of the mean CMI value). Volunteers in the G2 group, regardless of gender, presented not only lower HDL-c values but also higher weight, BMI, levels of total cholesterol, LDL-c, triglycerides, and the triglycerides to HDL ratio (TG/HDL) than the G1 group. The correlation analysis and linear multivariate regression, with CMI-adjustment, showed a significant positive association with BMI, as well as with pro-inflammatory cytokines, both in the G1 and G2 groups, regardless of gender. After that, the volunteers were separated according to BMI into normal weight and those with obesity. In general, the G2 subgroups with obesity showed higher levels of pro-inflammatory cytokines IL-1β, IL-6, IFN-γ, and TNF-α than the respective G1 subgroups, and also an association of CMI in favor of a pro-inflammatory systemic status, particularly in the older women group.
Conclusion: In this cross-sectional study, our findings not only reinforce the potential role of CMI in cardiovascular risk assessment but also may putatively suggest that this index has an interesting association with systemic pro-inflammatory status in older adults, preferentially with obesity.
Cancer survivors may have an accelerated biological aging process compared to cancer-free individuals. In this study, we aimed to investigate associations between clinical measures of biological aging and mortality (all-cause, cancer, and cardiovascular disease [CVD]) and examine whether the association between cancer history and mortality is mediated by biological aging. Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2010, with follow-up through 31 December 2019, were used. A total of 1,493 cancer survivors and 4,479 matched non-cancer individuals aged ≥20 years were included. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Biological age (BA) was measured by phenotypic age (PhenoAge) based on nine clinical biomarkers. The mediating effect of biological age was assessed using structural equation models with the bootstrapping method by estimating indirect (IE) and direct (DE) effects from cancer history to mortality. Compared to non-cancer individuals, cancer survivors had accelerated PhenoAge. The association between cancer history and all-cause mortality risk was partially mediated by PhenoAge acceleration (HRIE = 1.02, 95% CI: 1.01-1.03). Accelerated PhenoAge also partially mediated the association between cancer history and cancer-specific mortality (HRIE = 1.06, 95% CI: 1.01-1.18). In particular, PhenoAge acceleration mediated 15.5% and 24.1% of the associations of cancer history with all-cause and cancer-specific mortality, respectively. Our results highlight the importance of decelerating the biological aging process among cancer survivors, which may improve survivorship and long-term health in this population.
Introduction: Human saliva contains numerous factors, including DNA, RNA, and protein, that may reflect the health status of the individual. Many of these factors are contained within extracellular vesicles (EVs). The contents of EVs are thought to mirror the cytoplasm of the cell of origin, providing insight into the health of the cell. We investigated the RNA content from EVs isolated from saliva (salEVs) to determine if we could detect transcripts associated with neurodegenerative conditions.
Methods: We characterized the RNA cargo of salEVs isolated from individuals over the age of 65 with normal cognition. The salEV RNA content was analyzed by RNA-seq and NanoString miRNA analysis.
Results: We found approximately 48.4% of the reads mapped to the human genome, with the remainder mapping to prokaryotic genomes. The transcripts included protein-coding RNA, long non-coding RNA, retrotransposons, and miRNAs. A significant number of the protein-coding transcripts were associated with pathways involved in neurodegenerative conditions. In addition, there was an enrichment of transcripts containing AP-2ε, HEYL, HES4, and TCFL5 transcription factor binding sites. We found that the lncRNA content was similar between samples, with PCBP1-AS1, TEX41, and PVT1 being the top represented transcripts. There were 286 miRNAs found in the salEV samples. The pathways predicted to be affected by the top represented miRNAs include Hippo signaling, TGF-β signaling, Wnt signaling, FoxO signaling, ErbB signaling, axon guidance, and mTOR signaling. We could detect retrotransposon transcripts from LINE, SINE, and LTR elements in salEVs. When compared to blood-derived EVs, salEVs showed greater representation of transcripts associated with neurodegenerative pathways.
Discussion: Our results indicate that salEVs contain transcripts that are associated with pathways involved in neurodegeneration. The presence of these transcripts in salEVs suggest that saliva may be used to screen for biomarkers of neurodegenerative diseases.
Background: It is of utmost importance to identify older adults at risk of cognitive impairment at the earliest possible stage. Previous research supports the potential of investigating step parameters and turn duration during Timed Up and Go (TUG) during single and dual-task (TUGdt) conditions to detect subtle impairment. The aim of this study was therefore to investigate the test-retest reliability and measurement error of novel outcomes related to TUG and two TUGdt tests, TUGdt-NA (naming animals) and TUGdt-MB (reciting months in reverse order), in older adults with perceived memory impairment.
Methods: Thirty-four participants (18 women, mean age 76) were included and assessed with TUG, TUGdt-NA and TUGdt-MB on two different occasions, 5-10 days apart. Tests were video recorded for data extraction of spatiotemporal step parameters and turn duration. Reliability of motor and cognitive outcomes were analyzed with intraclass correlations (ICC2.1), standard errors of measurement and minimal detectable change (MDC). The proportional measurement error was presented with MDC%.
Results: The results showed very good reliability (ICC2.1 ≥ 0.85) regarding total completion times, although the measurement error and proportional measurement error (MDC%) was higher during TUGdt conditions than TUG. The reliability of cognitive outcomes during TUGdt favored TUGdt-MB (ICC2.1 ≥ 0.77, MDC% ≤39.8). Step length was the step parameter with highest reliability (ICC2.1 ≥ 0.86) and lowest proportional measurement error (MDC% ≤21.4) across conditions, whereas turn duration showed good reliability during TUG and TUGdt-MB (ICC2.1 ≥ 0.74, MDC%≤38.9).
Conclusion: The results support the potential of including TUG and TUGdt outcomes in cognitive risk evaluations among older adults.
Trial registration number: Uppsala-Dalarna Dementia and Gait Project | ClinicalTrials.gov, identifier NCT05893524.
Telomeres, nucleoprotein structures located at the ends of chromosomes, maintain genomic stability and regulate cellular lifespan, particularly in immune cells. Telomere shortening, driven by cell division and limited telomerase activity, accelerates immune ageing and increases susceptibility to infectious diseases. Chronic infections like HIV and tuberculosis exacerbate telomere attrition through sustained immune activation and oxidative stress. This study presents a bibliometric review of research on telomere length and infectious diseases from 2005 to 2025. Data from the Web of Science Core Collection were analysed using VOSviewer and CiteSpace, software tools for visualising co-authorship, citation, and keyword networks, to assess publication trends, collaborations, and themes. A total of 123 publications were identified, showing steady growth with a 60% increase in publications from 2020 to 2022 during the COVID-19 pandemic. Leading journals included Frontiers in Immunology, PLoS ONE, and Scientific Reports. The United States produced the largest share of publications, followed by Canada and Spain, with notable contributions from the University of British Columbia and Université de Montréal. Influential authors such as Côté HCF, Pick N, and Maan EJ have advanced research, particularly in the areas of HIV and tuberculosis. Keyword analysis highlighted two dominant themes: immune ageing and infection-related stress. Malaria research was comparatively scarce, underscoring a gap for future investigation. These findings inform future research on telomere-targeted interventions and epidemiological studies aimed at enhancing infectious disease management. This review provides a comprehensive overview of the field's progress and identifies key areas for future investigation.
Background: To combat loneliness among elderly individuals, it is crucial to identify effective strategies that can alleviate the negative impact of loneliness on their overall well-being.
Objective: This study evaluated social support programs' impact on loneliness in community-dwelling older adults. The goal was to inform tailored interventions that decrease loneliness and improve quality of life.
Methods: We systematically searched ten electronic databases (EMBASE, PubMed, Cochrane Library, Web of Science, CNKI, Weipu, WanFang, CBM) from inception to December 31, 2023, with citation chasing. Included randomized controlled trials (RCTs) tested social support interventions for loneliness reduction. Two independent reviewers extracted participant details, study characteristics, interventions, and outcomes. The methodological rigor of the included studies was assessed by JBI critical appraisal checklists.
Results: Nineteen studies met inclusion criteria, with over half from China (n = 7) and the United States (n = 4). Meta-analysis showed that social support helped alleviate loneliness and the difference was statistically significant [SMD = -0.60, 95%CI (-1.00, -0.20), I 2 = 93%, P = 0.003, random effect model]. Subgroup analysis showed significantly lower loneliness scores in experimental groups at less than 3 months [SMD = -0.68, 95%CI (-1.31, -0.06), I 2 = 93%, P = 0.03, random effect model]. In addition, multiple-intervention groups also showed significantly lower scores versus controls. The combined result was [SMD = -1.26, 95%CI (-2.20, -0.32), I 2 = 97%, P = 0.008, random effect model].
Conclusion: Social support interventions effectively reduce loneliness among community-dwelling older adults. For practical application, community health professionals are encouraged to implement short-term (≤3 months) multicomponent programs that combine emotional, peer, and technological support, delivered through group counseling, tele-support, or structured social activities. Integrating these interventions into routine community nursing services and local age-friendly programs may enhance mental wellbeing and social connectedness among older adults.
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