Frontiers in aging最新文献

Autoimmune diseases, particularly those with early onset such as systemic lupus erythematosus, juvenile idiopathic arthritis, and type 1 diabetes, are paradoxically characterized by molecular and cellular features typically associated with aging. These include telomere shortening, mitochondrial dysfunction, epigenetic alterations, and skewed immune cell phenotypes, which are considered hallmarks of immunosenescence. This perspective explores the hypothesis that aberrant inflammasome activation, particularly of the NLRP3 complex, serves as a key upstream driver of premature immune aging in autoimmunity. We examine how chronic inflammasome signaling induces senescence through pro-inflammatory cytokine production and oxidative stress, reinforces the senescence-associated secretory phenotype (SASP), and perpetuates immune dysregulation. By reframing autoimmunity as a disorder of accelerated immune aging, we highlight emerging opportunities for therapeutic intervention using senolytics, inflammasome inhibitors, and lifestyle modifications. In addition, incorporating biomarkers of immune aging into clinical assessment may enable precision immunogerontology, particularly in pediatric populations where biological and chronological age may be dissociated. Elucidating the relationship between inflammasome signaling and immune senescence provides a critical framework for understanding autoimmune pathogenesis and for developing interventions that modify disease course by targeting age-associated mechanisms.

The nucleosome remodeling and deacetylase (NuRD) complex, well known for its ATP-dependent chromatin remodeling and histone deacetylation activities combined in one multi-subunit complex, plays an evolutionarily conserved role in chromatin structures and gene regulation during cell growth, proliferation, and development. However, the composition and function of the NuRD complex in planarians remain incompletely unknown. Here, we identified six core components within the NuRD complex and characterized their biological roles in planarians. RNA interference (RNAi) mediated knockdown of these genes resulted in similar perturbations to both tissue homeostasis and regeneration, and the overlapping downstream genes regulated upon depletion of MBD2/3 or CHD4 showed similar expression alterations to that after knockdown of other NuRD complex genes, suggesting that NuRD core members may act in one complex. Additionally, the overlapping upregulated genes after depletion of NuRD complex members were expressed in neoblast and progenitor cells, among which NuRD complex core genes were enriched, suggesting transcriptional correlation between the overlapping upregulated genes and NuRD core members. Furthermore, upstream regulatory sites of the upregulated genes exhibited significant enrichment of H3K27ac, indicating the NuRD complex may deacetylate histone to modulate these genes. Notably, depletion of either MBD2/3 or CHD4 in planarians significantly upregulated multiple progenitor marker genes while reducing the number of somatic cells in the epidermis and intestine and downregulating multiple somatic cell marker genes, indicating that the NuRD complex may drive differentiation into somatic lineages in planarians. Collectively, our work provides a foundation to understand the essential roles of the NuRD complex in orchestrating cell differentiation, tissue homeostasis and regeneration in planarian.

Background: Ageing trajectories for foreign-born individuals and women living with HIV remain poorly defined globally. This study aimed to characterize foreign-born women living with HIV aged ≥65 years (FWLH) and compare them to age-matched Italian women (IWLH) and foreign-born men living with HIV (FMLH).

Methods: Data were drawn from the multicenter Italian geriatric HIV cohort (GEPPO). We described sociodemographic characteristics, viro-immunological status, comorbidities, and multidimensional geriatric assessment in FWLH. A complete case analysis was supplemented by multiple imputation using the mice package with the Predictive Mean Matching (PMM) method, and pooled estimates were derived from regression models, that included an interaction term for sex × birthplace.

Results: We included 330 participants: 285 (86.5%) women, 15 (4.5%) FWLH and 30 (9%) FMLH. Comparing FWLH to IWLH, lower CD4+/CD8+ ratio (beta -0.38; 95% confidence interval (CI) -0.79, 0.03; p-value = 0.069) and percentage of CD4⁺ cell (beta -10; 95% CI -16, -4.1; p-value = 0.001) and higher weight (beta 11; 95% CI 3.4, 18; p-value = 0.004) and BMI (beta 3.8; 95% CI 0.57, 7.0; p-value = 0.021) were observed. Comparing FMLH to FWLH, we found lower prevalence of multimorbidity (IRR 0.60, 95% CI 0.37, 0.98, p-value = 0.039) and osteoporosis, though risk difference for osteoporosis was not significant. In the interaction model, FWLH had a lower percentage of CD4⁺ cells (β = -0.38; 95% CI: -0.73, -0.02; p = 0.036).

Conclusion: FWLH in a geriatric cohort showed a profile of immune imbalance and higher weight, BMI, and multimorbidity; this may be possibly related to a worse metabolic profile and poorer access to care. However, there was no difference in virological response and antiretroviral therapies. Enhancing our understanding of older FWLH is crucial for promoting person-centered care a patient-centred care and healthy ageing in this population.

Aging is a multifactorial process and a major risk factor for chronic disease. Among its hallmarks, mitochondrial dysfunction plays a central role, driven by impaired respiration and accumulated mitochondrial DNA mutations that disrupt energy metabolism and redox balance. Conventional mitochondrial transplantation has been explored as a therapeutic strategy, but its emphasis on increasing mitochondrial quantity without restoring function has limited success. Recent advances in nanoengineered mitochondria that integrate isolated mitochondria with functional nanomaterials, offer new opportunities to enhance organelle quality, boost metabolic activity, and achieve targeted delivery. Preclinical studies highlight their promise in cardiovascular, neurodegenerative, and other age-related disorders. In this mini-review, mitochondrial dysfunction in aging is first introduced, followed by the summary of rational designed strategies for engineering mitochondrial biohybrids and their emerging applications, and finally translational challenges are further discussed. By bridging materials science and mitochondrial therapy, nanoengineered mitochondria may represent a next-generation approach to anti-aging interventions.

Introduction: There is limited prior research on the physiological effects of sutra chanting.

Methods: The health effects of sutra chanting were explored by comparing the oral and respiratory functions of Buddhist priests who are experts in sutra chanting with those of general Buddhist priests. In addition to basic characteristics, lifestyle variables, and general health status, participants underwent assessment of oral function and respiratory function by two certified dentists.

Results: Compared to general priests (n = 23), expert chanters (n = 49) were significantly higher in peak expiratory flow (PEF), forced vital capacity (FVC), and hyoid displacement (⊿HD). In the two multiple regression analyses which include PEF and FVC as the dependent variables, expert group demonstrated significantly better function.

Discussion: Considering its historical and cultural background, the idea of using sutra chanting has potential in a healthcare program for older people at risk of declining oral and respiratory functions.

Background: Cognitive decline is prevalent among older adults and may be associated with their daily activity behaviours. However, no studies have examined how cognitive decline affects older adults' activity behaviours within a 24-h framework. This study investigates the relationship between cognitive function and 24-h activity behaviours in older adults, further exploring whether these associations differ by sex.

Method: This study analyses data from the eighth wave of the Survey of Health, Ageing and Retirement in Europe, conducting a cross-sectional analysis of 814 older adults. Cognitive function was assessed using the SHARE-Cog tool, encompassing 10-word immediate recall, 10-word delayed recall, verbal fluency, and self-reported memory. 24-h activity behaviours (moderate-to-vigorous physical activity [MVPA], light physical activity [LPA], sedentary behaviour [SB], and sleep) were objectively measured with thigh-worn accelerometers. Compositional multivariate linear regression models were constructed using compositional data as the response variable, with cognitive function measures as predictors.

Results: Higher MVPA was linked to better cognitive outcomes (verbal fluency, 10-word immediate recall, and 10-word delayed recall) while SB and longer sleep related to poorer performance, with these associations being stronger in women (model p ≤ 0.001). Among women, cognitive outcomes were significantly associated with all activity behaviours (p range = 0.010-0.045). Women who self-reported poor memory and scored 0 on the verbal fluency spent approximately 45% of their day in SB, whereas those reporting excellent memory and scoring 60 spent 40.06% (37.18%, 42.86%) and 36.41% (31.53%, 41.10%) of their day sedentary, respectively. In contrast, men's 24-h activity composition did not vary significantly with cognitive function (p range = 0.051-0.845).

Conclusion: Older adults with better cognitive function tend to engage in more PA and reduce sedentary and sleep time. This relationship differed by sex, with females' activity behaviours being more sensitive to cognitive function changes.

Implications: These findings suggest that interventions promoting healthy lifestyles in older adults should account for cognitive function, particularly in females.

Introduction: Arterial aging is an independent risk factor for cardiovascular morbidity and mortality and is beneficially influenced by physical activity. However, it remains unclear whether the impact of physical activity on arterial stiffness differs between men and women and whether selected factors contribute to sex differences in the association of physical activity with arterial aging.

Methods: Data from healthy volunteers (n = 265; mean age: 40 ± 16 years, 42.6% women) were used. Arterial aging was assessed using carotid-to-femoral pulse wave velocity (PWV). Volunteers were categorized as sedentary (no regular weekly physical activity) and regularly active.

Results: Physically active men presented a significantly lower PWV than the sex-matched sedentary group (8.2 ± 0.2 versus 9.0 ± 0.3 m/s, p < 0.01). In the fully adjusted model (adjusted for age, blood pressure, heart rate, muscular mass, fat mass, and visceral adiposity), a steeper association between PWV and autonomic nervous system activity was observed in sedentary individuals than in physically active men. Physical activity was associated with no difference in PWV (7.9 ± 0.3 versus 7.9 ± 0.2 m/s), and no significant association between PWV and autonomic nervous system activity was observed in women.

Conclusion: Physical activity was associated with a lower increase in arterial aging, indexed as pulse wave velocity, for any increase in autonomic nervous system activity in men. This effect was independent of age, blood pressure, and adiposity. The same effect was not observed in women. Future studies should clarify how these findings may inform a personalized approach to cardiovascular (CV) risk reduction.

Introduction: Although the relationship between functionality, as reflected in physical performance (PHP), and mental health in older adults has been researched, its strength remains unclear.

Methods: This field study aimed to determine the strength of this relationship in adults aged 60 and above using seven PHP indices and six psychological measures. We individually tested 114 older adults. Objective measures included six PHP indices consisting of the Senior Test and handgrip strength. Subjective measures included resilience, wellbeing, happiness, perceived stress, hopelessness, and life satisfaction.

Results: Structural equation modeling (SEM) revealed two latent constructs: PHP and mental wellbeing (MWB): robust fit (MLR): X² (75) = 136.28, p < 0.001; CFI = 0.967; TLI = 0.960; RMSEA = 0.066 (90% CI [0.000, 0.128]); SRMR = 0.088. The latent partial correlation between PHP and MWB (adjusted for Age) was φ = 0.46, indicating ∼21% shared variance. The correlation between the two latent factors was moderate (r = 0.46), suggesting that other unassessed factors might account for the relationship.

Discussion: Based on objective PHP and subjective MWB measures, these results suggest a modest connection, with the two latent constructs sharing ∼1/5 of their variances. Consequently, further research is needed to identify other factors affecting the studied relationship in older adults. These cross-sectional findings, suggesting a moderate association, should be interpreted with caution. Still, they support recommending physical activity as one component of broader, multi-domain strategies to support the wellbeing of older adults.

Background: The increased prevalence of obesity and incidence of lung cancer have raised significant concerns worldwide. However, the relationship between obesity and lung cancer risk, and the potential mediating effect of biological aging remains poorly understood.

Methods: Using UK Biobank database, this population-based cohort study employed multivariable Cox regression to estimate HRs (Hazard Ratios) for obesity indices (waist circumference [WC], waist-hip ratio [WHR], body shape index [ABSI], conicity index [C-Index]) and lung cancer risk. Biological aging was evaluated via PhenoAge and Klemera-Doubal method age (KDMAge), with acceleration calculated by regressing biological on chronological age. Longitudinal mediation analysis explored their mediating effects.

Results: Among the 301,398 participants in the study, 2,466 incident cases of lung cancer were identified. All central - obesity - related indices were significantly associated with elevated risk of lung cancer, with (WC: HR = 1.10, 95% CI 1.02-1.19; WHR: 1.10, 1.03-1.18; ABSI: 1.73, 1.54-1.94; C-Index: 1.51, 1.35-1.69). Notably, PhenoAge/KDMAge acceleration mediated the associations between WHR, ABSI, C -Index and the lung cancer risk, with mediated proportions from 1.85% to 32.67%.

Conclusion: This study highlights central obesity was significantly associated with incident risk of lung cancer, emphasizing biological aging's mediating role.

Introduction: The aging process profoundly influences not only the health and visual appearance of the skin, but also the composition of the microbial communities residing on its surface.

Methods: To investigate these microbial changes, we employed a comprehensive, multi-scale approach that probes community composition, species interactions, and predicted metabolic function of the skin microbiome of the face and forearm in young and old age individuals from the United Kingdom using 16S rRNA gene sequencing.

Results: Our findings revealed significant and site-specific age-related shifts in the microbiome involving diversity, interpersonal heterogeneity, network connectivity, and metabolic potential, suggesting loss of microbiome robustness and a shift towards a hyperdiversified, fragile microbial community in old age. Furthermore, we applied Dirichlet Multinomial Mixtures to uncover novel age-driven microbiome profiles unique across each skin site, highlighting Cutibacterium acnes, Staphylococcus hominis, and microbial community diversity as key differentiating biomarkers of the skin microbiome across the lifespan.

Discussion: Overall, through examining the aging skin microbiome from a systems perspective, our study reinforces and enhances the findings from previous aging microbiome studies and underscores the importance of site-specific differences in skin microbiome dynamics with age. These insights suggest that microbial interventions could mitigate age-related changes, enhancing skin health and wellbeing throughout life.