GeroScience最新文献

Psycho-socio-economic factors (PSEFs) such as income and homeownership may influence the prevalence of cardiorenal multimorbidity (CRM), yet their prospective associations with CRM risk remain unclear. This study aimed to estimate CRM incidence and examine its relationships with multiple PSEFs in a nationally representative Canadian cohort. We analyzed data from 16,557 participants (mean age: 60.4 years; 48.9% men) in the Canadian Longitudinal Study on Aging (CLSA) who were free of CRM at baseline (2010-2015). Incident CRM was defined as the co-occurrence of at least one cardiovascular disease and kidney disease at second follow-up (2018-2021). Survey-weighted multivariable logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for PSEFs and CRM risk. Over 3-11 years follow-up, 194 participants (1.2%) developed CRM, corresponding to 8.80 per 1,000 individuals (95% CI: 6.77-11.40). CRM incidence increased with age, was higher in men than women (10.63 vs. 7.35 per 1,000), urban than rural residents (9.69 vs. 3.72 per 1,000), and immigrants than non-immigrants (10.87 vs. 8.49 per 1,000). Greater tangible social support reduced CRM risk (OR = 0.65; 95% CI: 0.43-0.97), while depression (OR = 1.68; 95% CI: 1.07-2.65) and PTSD (OR = 3.14; 95% CI: 1.74-5.67) increased risk. In middle- to older-aged Canadian adults, higher social support appears protective, whereas depression and PTSD increase CRM risk. Although incidence was low, CRM burden rose with age and was higher among men, urban residents and immigrants. These findings highlight the importance of psychosocial well-being and social connectedness in preventing CRM and reducing multimorbidity burden in aging populations.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population. Although frailty has been recognized as a potential risk factor, previous studies relying on static assessments cannot capture its dynamic nature. This study aims to prospectively evaluate the association between dynamic frailty trajectories and incident AMD. The baseline cohort included 462,573 UK Biobank participants who were free of AMD and had frailty phenotype (FP) data at enrollment. Among them, 53,059 with at least one follow-up FP assessment comprised the trajectory cohort. Participants were categorized as nonfrail, prefrail, or frail based on their FP scores. Annualized frailty progression (ΔFP/year) was estimated via linear regression. Cox models assessed hazard ratios (HRs) and 95% confidence intervals (CIs) for AMD. During a median follow-up of 11.8 years in the baseline cohort, 13,428 incident AMD cases (2.9%) were documented. Prefrail (HR:1.14; 95% CI:1.10-1.18) and frail (HR:1.36; 95% CI: 1.26-1.47) individuals had significantly higher AMD risks compared to nonfrail participants. In the frailty trajectory analysis with a median follow-up duration of 3.3 years, 852 incident AMD cases (1.6%) were recorded. Each 1-point FP increase conferred 28% higher AMD risk (HR: 1.28; 95% CI: 1.18-1.38), while each 0.1-point/year ΔFP increase independently elevated risk by 15% (HR: 1.15; 95% CI: 1.10-1.21). Compared to stable nonfrail, prefrailty aggravation showed highest AMD risk (HR: 2.26; 95% CI: 1.51-3.37), followed by frailty alleviation (HR: 1.73; 95% CI: 0.98-3.04) and frailty maintenance (HR: 1.72; 95% CI: 0.86-3.41). Progressive frailty trajectories, independent of baseline status, is associated with increased incident AMD risk. Early interventions targeting frailty progression may mitigate AMD risk in aging populations.

Hypoglossal motor neurons (MNs) within the medullary hypoglossal nucleus innervate the striated muscles of the intrinsic and extrinsic tongue. Dysfunction of the control of the tongue muscles may lead to problems such as dysphagia, dysphonia and the increased risk of aspiration pneumonia in the elderly. In the human and Fischer 344 (F344) rat motor systems, age-related muscle weakness and behavioural dysfunctions are contemporaneous to MN death. In other neurons, dendritic and mitochondrial degenerations are fundamental pathophysiological components preceding neuronal death. We aimed to determine if dendritic, dendritic spine and dendritic mitochondrial pathology were present in old age. We used golgi-cox and serial block-face scanning electron microscopy (SBFSEM) to evaluate dendritic and mitochondrial morphology, respectively in young (6-month) and old (24-month) female and male F344 rats. Dendritic regression and dendritic spine loss occurs in old age, predominantly in larger hypoglossal MNs. In addition, reduced dendritic mitochondrial volume density and mitochondrial fragmentation are apparent in old age. Our results are consistent with established age-related deficits in F344 rats, including tongue muscle sarcopenia, hypoglossal MN loss and dysphagia. Although more work is needed to determine if synaptic and mitochondrial degenerations are causative for age-related neuromotor dysfunctions, our results suggest that strategies to preserve dendrites and mitochondria may be of therapeutic utility.

Social support has been related to cardiovascular disease (CVD) incidence and mortality in longitudinal cohort analyses, but the biological pathways underpinning this remain underexplored. This exploratory study examined the associations between social support and a wide range of proteomic biomarkers and performed the mediating effect of proteomic biomarkers in the association between social support and CVD and mortality to identify potential biological pathways linking social support to health outcomes. Data from 3141 adults over the age of 50 in the English Longitudinal Study of Ageing who had plasma proteome data were analyzed, with CVD and mortality outcomes followed up for 16 years following through Hospital Episode Statistics and the National Health Service's Central Registry. Linear and Cox regression analyses were used to identify proteins associated with social support, CVD, and mortality. Mediation analysis was then performed on the identified proteins to explore their role as a potential mediator between social support and CVD and mortality risk. Over a median of 15.8-year follow-up, 889 participants have died, and 627 developed CVD. Of 276 plasma proteins measured, greater social support was associated with lower levels of 13 proteins and higher TN-R levels, after adjusting for baseline socioeconomic confounders. We also identified 49 protein-CVD and 70 protein-mortality associations after minimal adjustments, including 11 and 14 proteins simultaneously associated with social support. All the significant proteins together mediated about 20.9% and 26.4% of the associations for CVD and mortality, respectively. The main enriched biological pathways involved death receptor activity and carbohydrate binding. Social support was related to a cluster of proteomic biomarkers, which may be linked to inflammation, apoptosis, and atherosclerosis/vascular pathways. The identified plasma proteins partly mediated the association between social support and CVD and mortality risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between relationship quality, proteomic signatures, and CVD and mortality development.

Age-related hearing loss (ARHL) is a common health problem that impairs auditory perception. However, the dynamic patterns of brain functional connectivity in ARHL during auditory spatial selective attention have not been thoroughly investigated. In this study, 32 older adults were recruited to investigate the dynamic brain functional connectivity in ARHL. First, an experimental paradigm for auditory spatial selective attention was designed, and neural electrical signals were recorded using electroencephalography. Then, a multilayer time-varying brain network was constructed based on multiple time windows, equally dividing each epoch signal to capture dynamic functional connectivity across time scales. Finally, the core layer brain network was identified by the multilayer time-varying brain network properties to investigate the changing patterns of network topology. Behavioral analysis revealed a significant negative correlation between the severity of hearing loss and auditory spatial selective attention performance. Multilayer time-varying brain network analysis revealed that worsening hearing loss was found to lead to increased inter-layer connectivity strength, decreased multilayer modularity and a higher participation coefficient. This suggests that the brain compensates by weakening the independence of local functional modules and enhancing cross-interaction. Core layer analysis further highlighted the critical role of the right parietal lobe in auditory spatial selective attention. It also suggested that connectivity between the right prefrontal and frontal lobes may play a compensatory role in ARHL. In conclusion, these findings provide important neuroscientific insights into the dynamic brain functional connectivity of ARHL, and potential biomarkers and time windows for the development of precision auditory rehabilitation strategies.

The ability to suppress irrelevant or distracting inputs that interfere with goal-driven behavior is known to decline with increasing age. Although noninvasive stimulation of the motor cortices has been shown to modulate age-related changes in motor activity, the findings remain preliminary, and it is unknown whether this effect extends beyond the motor cortex. In this study, 125 healthy adults, categorized into young (20-35 years) and older groups (55-72 years) underwent three visits (i.e., anodal, cathodal, and sham). During each visit, they received 20 min of high-definition transcranial direct current stimulation (HD-tDCS) applied to their left primary motor cortex (M1) and completed a flanker task during high-density magnetoencephalography (MEG). Statistically significant oscillatory responses were imaged and analyzed using voxel-wise, whole-brain, and point of stimulation approaches. Our results showed increased gamma flanker interference effects within the contralateral M1 in older relative to younger adults following anodal stimulation, and after anodal compared to cathodal HD-tDCS in older adults. We also found polarity-based differences in beta and gamma M1-prefrontal connectivity as a function of age group. Critically, these data indicate distinct spectrally- and polarity-dependent effects of M1 HD-tDCS on the local and network-level neurophysiological responses serving motor performance in young versus older healthy adults.