Frontiers in aging最新文献

This paper presents a comparative analysis of the relationship between aging, the epigenetic program of ontogenesis, and the main postulates of the hyperfunction theory. The discussion highlights points of convergence between these frameworks and proposes a unified interpretation. According to the hyperfunction theory, aging arises from the continued activity of growth and regulatory pathways after reproductive maturity, as more cells shift from proliferation to functional maintenance while retaining high metabolic and signaling activity. However, this process does not represent a simple enhancement of specialized cellular functions. Instead, it reflects a redistribution of intracellular resources from self-sufficiency to the performance of specialized functions. Building on earlier findings on genome methylation dynamics, we argue that the epigenetic program of ontogenesis regulates primarily the genomic regions responsible for cell differentiation. This unbalanced regulation results in a gradual drift of the active epigenetic landscape toward maladaptation. Consequently, the hyperfunctional state observed during aging is not the primary cause but a downstream effect of this one-sided epigenetic influence. Thus, the main cause of aging is not software errors in old age, but the lack of feedback between the activity of domestic and specialized genes in the body's cells. The approach presented in the article points to the promise of new approaches to rejuvenation based on restarting the epigenetic program of cells. This direction is aimed at restoring the balance of genomic activity underlying aging and offers potential measures to restore genomic balance.

Introduction: Age-related hearing loss (ARHL) frequently coexists with balance disorders in older persons, but the mechanisms and rehabilitative leverage of this association remain unsettled. We synthesized evidence on interactions between ARHL and vestibular/gait dysfunction, quantified mobility and fall outcomes, and appraised clinical implications for prevention.

Methods: Following PRISMA and a registered PROSPERO protocol, we searched PubMed (MEDLINE), Scopus and Web of Science Core Collection. Inclusion required adults ≥65 years, ARHL and quantitative vestibular/balance outcomes. Forty studies met the criteria. Vestibular pooling was infeasible due to heterogeneous designs and metrics. In quantitative analysis, continuous outcomes were meta-analysed as standardized mean differences (SMD) (Hedges g) using random effects (REML) for ARHL-control contrasts and a fixed effect for within-participant Hearing Aid (HA) ON-OFF contrasts. For falls, we pooled Odds Ratio (OR) with REML.

Results: Five out of seven studies linked ARHL to vestibular impairment. Across six studies, ARHL was associated with slower Timed Up to Go (SMD = -0.679), yet meta-regression showed systematic bias from age imbalance (-0.036 SMD per year older in HL), and the adjusted intercept was not significant. In three HA ON-OFF studies, static posturography improved with amplification (g = 0.459). The falls meta-analysis (k = 4; follow-up 12-60 months) showed higher fall odds with ARHL (OR = 1.55).

Discussion: Age is a dominant driver of mobility, but ARHL contributes modifiable risk through sensory and cognitive-motor pathways. Consistent improvements with HA and converging gait data support integrating auditory rehabilitation-alongside vestibular/sensory-integration training-into multimodal fall-prevention strategies. Standardized protocols and age-balanced trials are priorities to refine effect estimates and clarify mechanisms.

Introduction: Establishing a nationwide prevention programme can be challenging, particularly in the field of dementia, as role model projects are lacking, and the topic is still associated with stigma. Hence, a satisfaction survey for the programme dementia prevention (pdp) in Luxembourg was conducted to obtain direct feedback from the participants on how the programme and its multidomain interventions are accepted and evaluated.

Methods: In 2023 and 2024, a satisfaction survey was sent out to all eligible pdp participants (n = 575). Participation was voluntary and anonymous, and the survey could be completed in paper form or online. The questionnaire contained 12 closed-ended questions rated on a Likert-scale and 3 open questions.

Results: 302 (52.5%) participants returned the survey. The analysis revealed a high level of satisfaction with an overall average satisfaction of 4.7/5 points (SD = 0.6). 281 participants (95.9%) would recommend the pdp to others. A breakdown of the statements provided insights into areas of interest from the participants' perspective.

Discussion: Our study shows that the pdp is well received by its participants, underlined by a high level of satisfaction and positive responses to what pdp offers. Findings showed that interactions were perceived as informative to gain insights into one's own cognitive performance and raised awareness of possibilities to reduce dementia risk, i.e., via lifestyle changes. Our results can serve as orientation for the implementation of emerging prevention programmes in different healthcare settings.

Objective: This study aimed to develop and validate a novel risk score for death within the next 3 months in patients with maintenance hemodialysis (MHD).

Methods: All the data were derived in the Wuhan Hemodialysis Quality Control Center and were divided into the training set (2019-2021, n = 19,735) and the validation set (2022-2023, n = 15,265). The primary outcome was the all-cause mortality within 3 months after regular monthly laboratory tests. The predictive model was displayed as a nomogram and modified into a novel scoring system based on the coefficients of multivariable logistic regression.

Results: There were 1684 (8.5%) patients and 1670 (10.9%) patients who died in the development and validation set, respectively. The final novel score system was calculated based on the five predictors: age ≥60 years (2 points), dialysis duration <1 year (2 points), catheter usage (1 point), hemoglobin <110 g/L (1 point), and albumin <35 g/L (3 points). This model with a C-index of 0.72 and 0.73 on the two sets and exhibited a significant ability in stratification of patients into low-risk, intermediate-risk, and high-risk groups (P < 0.0001).

Conclusion: This easy-to-use applicable scoring system accurately predicts 3-month mortality in HD patients, facilitating risk stratification and personalized care.

Our world is facing a global aging crisis with an increasing number of people living longer in poor health, as indicated by a gap between lifespan and healthspan. It is necessary to improve our knowledge of the biomolecular and cellular pathways implicated in aging to improve the overall healthspan of the population and lift the economic and social burden of age-related diseases. Gerontologists have defined twelve hallmarks of aging to study them efficiently. Here we review each aging hallmark in the context of N. furzeri, a short-lived model fish. Introduced to the lab in 2003, this fish has the shortest vertebrate lifespan recorded in captivity. Depending on the strain, it lives between 2 months to 1 year. While aging, it develops several age-related phenotypes experienced by humans, such as emaciation, spine curvature, locomotor and cognitive defects. We summarize that aged Nothobranchius furzeri develop characteristics of each hallmark with high similarity to humans and other aging models. For several of these hallmarks, interventions that accelerate aging clearly leads to reduced health and a shorter lifespan, expanding our knowledge on molecular mechanisms favoring shorter healthspan. Interventions that decelerate aging have demonstrated a positive impact on health or an extension to lifespan, that could be transferred to humans for an increased healthspan. For example, the link between glucose metabolism and ER stress or the use of young microbial gut transplant to improve health are two discoveries made in N. furzeri and are of relevant importance for human healthy aging. By comparing similar ages and strains and by using standardized breeding procedures, the N. furzeri community will continue to greatly contribute to aging research. Creating stable transgenic lines and finding a way to administer drugs efficiently are two challenges that must be addressed to test novel targets of interests or therapies in each hallmark of aging.

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.