GeroScience最新文献

Rheumatoid arthritis (RA) is an age-related chronic inflammatory disease which may include accelerated biological ageing processes in its pathogenesis. To determine if increased biological age is associated with risk of RA and/or is present once disease is established. We used DNA methylation to compare biological age (epigenetic age) of immune cells in adults at risk of RA and those with confirmed RA, including twins discordant for RA. The established RA studies were secondary analyses of existing DNA methylation data. Sub-group analysis considered the influence of ethnicity. Four epigenetic clocks were used to determine DNA methylation age. DNA methylation age was no different in adults at risk of RA in the Leiden Clinically Suspect Arthralgia (CSA) cohort (n = 38 developed RA, n = 24 did not), and there was also no difference in DNA methylation age between 77 UK twins discordant for RA, or adults with established RA from the Swedish EIRA cohort (n = 342) compared to healthy controls (n = 328). A sub-group analysis of RA patients of South Asian ethnicity (10 RA patients, 14 healthy controls) showed DNA methylation age acceleration of 3.3 years (p = 0.00014) using the mean DNA methylation age of four epigenetic clocks. Our study suggests that epigenetic age acceleration may be differentially influenced by South Asian ethnicity, but that RA was not generally associated with accelerated epigenetic age. The higher epigenetic age in the South Asian patients may explain the earlier age of onset in this minority ethnic population.

Age-related cognitive impairment and dementia pose a significant global health, social, and economic challenge. While Alzheimer’s disease (AD) has historically been viewed as the leading cause of dementia, recent evidence reveals the considerable impact of vascular cognitive impairment and dementia (VCID), which now accounts for nearly half of all dementia cases. The Mediterranean diet—characterized by high consumption of fruits, vegetables, whole grains, fish, and olive oil—has been widely recognized for its cardiovascular benefits and may also reduce the risk of cognitive decline and dementia. To investigate the protective effects of the Mediterranean diet on cognitive health, we conducted a systematic literature review using PubMed, Web of Science, and Google Scholar, focusing on studies published between 2000 and 2024. The studies included in the meta-nalysis examined the adherence to the Mediterranean diet and the incidence of dementia and AD. We applied a random-effects model to calculate pooled hazard ratios (HRs) with 95% confidence intervals (CIs) and assessed heterogeneity through I-square statistics. Forest plots, funnel plots, and Z-score plots were used to visualize study outcomes. Of the 324 full-text records reviewed, 23 studies met the inclusion criteria. The combined HR for cognitive impairment among those adhering to the Mediterranean diet was 0.82 (95% CI 0.75–0.89); for dementia, the HR was 0.89 (95% CI 0.83–0.95); and for AD, the HR was 0.70 (95% CI 0.60–0.82), indicating substantial protective effects. Significant heterogeneity was observed across studies, though Z-score plots suggested sufficient sample sizes to support reliable conclusions for each condition. In conclusion, this meta-analysis confirms that adherence to the Mediterranean diet is associated with an 11–30% reduction in the risk of age-related cognitive disorders, including cognitive impairment, dementia, and AD. These findings underscore the Mediterranean diet’s potential as a central element in neuroprotective public health strategies to mitigate the global impact of cognitive decline and dementia and to promote healthier cognitive aging.

Increasing evidence suggests that Lewy body disease (LBD) is associated with clinically important cardiac complications, including sick sinus syndrome, atrial fibrillation and sudden cardiac death. The high prevalence of sick sinus syndrome and atrial fibrillation in LBD suggests the presence of disease-related atrial conduction disorders. To explore whether LBD is associated with atrial conduction disorders, electrocardiographic (ECG) P wave parameters were analyzed in a cohort of LBD patients (n = 74), using age-matched Alzheimer’s disease (AD) patients (n = 25) as controls. P wave terminal force in V1 and P wave duration were found to be significantly greater in the LBD group than in the AD group. In addition, 43 (58%) individuals in the LBD exhibited pathological P wave terminal force (> 4000 µV*ms) vs 3 (12%) in the AD group, and 60 (81%) in the LBD group exhibited pathological P wave duration (≥ 120 ms), vs 13 (52%) in the AD group. The difference could not be explained by atrial fibrillation or atrial enlargement on echocardiogram. The clinical significance of pathological P wave parameters in LBD is unknown, but their presence suggests an atrial cardiomyopathy that could be due to cardiac alpha-synuclein deposition, autonomic dysfunction, or a combination thereof. Future research is warranted to elucidate whether this proposed disease-related atrial cardiomyopathy is related to cardiac alpha-synuclein deposition, whether it is causally related to cardiac complications in LBD, and whether pathological P wave parameters hold potential as a screening tool for cardiac complications in LBD.

Unintentional weight loss in older populations is linked to greater mortality and morbidity risks. This study aims to understand the metabolic mechanisms of unintentional weight loss and their relationship with body composition changes in older adults. We investigated plasma metabolite associations with weight and body composition changes over 5 years in 1335 participants (mean age 73.4 years at Year 1, 51% women, and 33% Black) from the Health, Aging and Body Composition (Health ABC) study. Multinomial logistic regressions were used to examine associations of the 442 metabolites with weight loss > 5% over 5 years with/without an intention, weight gain > 5%, and fluctuating weight relative to weight stability. Metabolite associations with unintentional weight loss differed from other weight change patterns. Lower levels of essential amino acids, phospholipids, long-chain polyunsaturated triglycerides, cholesterol esters, and uridine were associated with higher odds of unintentional weight loss versus weight stability after adjusting for age, sex, race, and Year 1 BMI categories. Losses in fat mass and muscle mass each attenuated > 20% of the associations between many metabolites, such as phospholipids and essential amino acids, and unintentional weight loss. DXA whole-body fat mass loss (mean 3% annually) further attenuated 9 metabolite associations by > 50% after CT muscle loss (mean 2% annually) adjustment. Lipids and amino acids related to energy and protein balance were associated with unintentional weight loss in older adults. Fat and muscle mass losses partially attenuated these associations, suggesting connections of these metabolic pathways with muscle, and particularly adiposity dynamics.

Background

Rapid eye movement (REM) sleep behavior disorder (RBD) is an early and significant prodromal marker for Parkinson’s disease (PD). While the association between RBD and PD has been well-documented, the underlying pathophysiology differentiating PD patients with RBD (PD-RBD +) from those without RBD (PD-RBD-) remained unclear. This study aims to investigate the possible relationship between RBD and striatal dopamine depletion in de novo PD patients.

Methods

A retrospective, cross-sectional study was conducted on 151 PD patients. We used standard questionnaires and measurements to assess motor and nonmotor symptoms. The dopaminergic function was assessed utilizing Tc-99 m TRODAT-1 SPECT imaging, and statistical analyses were performed to compare dopamine transporter (DAT) binding between patients with or without probable RBD (pRBD).

Results

The PD-pRBD + group exhibited significantly lower DAT binding in the caudate nucleus (OR 0.618; 95% CI 0.392–0.618; p = 0.039) and putamen (OR 0.554; 95% CI 0.319–0.962; p = 0.036) compared to the PD-pRBD- group. The PD-pRBD + group also had a higher prevalence of non-motor symptoms, including depression (OR 7.499; 95% CI 2.770–20.299; p < 0.001) and constipation (OR 2.356; 95% CI 1.090–5.092; p = 0.029). Although trends toward increased dementia (12.3% in PD-pRBD + , 6.4% in PD-pRBD-, p = 0.266) and falls (16.4% in PD-pRBD + , 11.5% in PD-pRBD-, p = 0.482) were observed in the PD-pRBD + group, these did not reach statistical significance.

Conclusion

The presence of RBD in PD patients is associated with greater striatal dopaminergic dysfunction, suggesting a distinct subtype with potentially faster disease progression. These findings highlight the importance of early RBD identification in PD patients to guide more personalized interventions.

With the development of deep learning (DL) techniques, there has been a successful application of this approach to determine biological age from latent information contained in retinal images. Retinal age gap (RAG) defined as the difference between chronological age and predicted retinal age has been established previously to predict the age-related disease. In this study, we performed discovery genome-wide association analysis (GWAS) on the RAG using the 31,271 UK Biobank participants and replicated our findings in 8034 GoDARTS participants. The genetic correlation between RAGs predicted from the two cohorts was 0.67 (P = 0.021). After meta-analysis, we found 13 RAG loci which might be related to retinal vessel density and other aging processes. The SNP-wide heritability (h²) of RAG was 0.15. Meanwhile, by performing Mendelian randomization analysis, we found that glycated hemoglobin, inflammation hemocytes, and anemia might be associated with accelerated retinal aging. Our study explored the biological implications and molecular-level mechanism of RAG, which might enable causal inference of the aging process as well as provide potential pharmaceutical intervention targets for further treatment.

Graphical Abstract

Glucagon-like peptide-1 receptor (GLP-1R) agonists, such as exenatide (Byetta, Bydureon), liraglutide (Victoza, Saxenda), albiglutide (Tanzeum), dulaglutide (Trulicity), lixisenatide (Lyxumia, Adlyxin), semaglutide (Ozempic, Rybelsus, Wegovy), and tirzepatide (Mounjaro, Zepbound), are widely used for the treatment of type 2 diabetes mellitus (T2DM) and obesity. While these agents are well known for their metabolic benefits, there is growing interest in their potential effects on cancer biology. However, the role of GLP-1R agonists in cancer remains complex and not fully understood, particularly across different tumor types. This study aimed to evaluate the prognostic significance of GLP1R expression on overall survival across various cancer types. Using a comprehensive analysis of gene expression data and survival outcomes a large cohorts of different tumor types, we employed Cox proportional hazards survival analyses, coupled with false discovery rate determinations, to explore correlations between GLP1R expression and survival. The integrated database included thousands of cancer specimens with available overall survival time and event data from numerous independent cohorts, providing a robust platform for survival analysis. Our findings reveal that increased GLP1R expression is associated with improved overall survival in cancers such as bladder cancer, breast cancer, esophageal adenocarcinoma, renal clear cell carcinoma, and thyroid carcinoma. Conversely, higher GLP1R expression is linked to poorer survival outcomes in cervical squamous cell carcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Additionally, GLP1R expression showed no significant impact on overall survival in cancers such as esophageal squamous cell carcinoma, colon cancer, head-neck squamous cell carcinoma, renal papillary cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, ovarian cancer, and pancreatic cancer. In conclusion, GLP1R expression levels serve as an important biomarker with potential prognostic significance across multiple cancers, demonstrating both protective and adverse associations depending on the tumor type. These findings highlight the complex role of GLP-1R agonists in cancer risk and survival, suggesting that the therapeutic use of these agents should be carefully tailored to the individual patient’s cancer risk profile.

Stroke is a leading cause of morbidity and mortality worldwide, and dietary patterns have emerged as a significant modifiable factor in stroke prevention. The Mediterranean diet, characterized by high intake of fruits, vegetables, whole grains, nuts, olive oil, and fish, has been widely recognized for its cardiovascular benefits. However, its specific impact on stroke risk requires further elucidation. We conducted a comprehensive meta-analysis of 30 studies, including both cohort and case–control designs, to evaluate the relationship between adherence to the Mediterranean diet and the risk of stroke. A systematic search was performed across multiple databases, and a random-effects model was used to estimate pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic, and publication bias was examined through funnel plots and Egger’s regression test. Additionally, trial sequential analysis was conducted to determine the adequacy of the sample size. The meta-analysis revealed a significant reduction in stroke risk among individuals adhering to the Mediterranean diet, with a pooled HR of 0.88 (95% CI: 0.84–0.91). Notably, a significant heterogeneity was detected (I² = 34%). The Z-score plot from trial sequential analysis confirmed that the sample sizes were sufficient to draw definitive conclusions. However, a potential publication bias was identified. The case–control studies confirmed a highly significant effect (HR = 0.54, 95% CI: 0.4–0.73). The funnel plots in both settings hinted at the presence of a potential publication bias, supported by a significant Egger’s test. Our findings provide robust evidence supporting the protective effect of the Mediterranean diet against stroke. Despite the presence of some heterogeneity and potential publication bias, the cumulative evidence suggests that promoting the Mediterranean diet could serve as an effective public health strategy for stroke prevention. Further research is recommended to explore the underlying mechanisms and to assess the diet’s impact across diverse populations.

Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase of SARS-CoV-2 infection, affecting approximately 10% to over 30% of those infected. It presents a significant clinical challenge, notably due to pronounced neurocognitive symptoms such as brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing to a central role of cerebromicrovascular dysfunction. This review investigates key pathophysiological mechanisms contributing to cerebrovascular dysfunction in long COVID and their impacts on brain health. We discuss how endothelial tropism of SARS-CoV-2 and direct vascular infection trigger endothelial dysfunction, impaired neurovascular coupling, and blood–brain barrier disruption, resulting in compromised cerebral perfusion. Furthermore, the infection appears to induce mitochondrial dysfunction, enhancing oxidative stress and inflammation within cerebral endothelial cells. Autoantibody formation following infection also potentially exacerbates neurovascular injury, contributing to chronic vascular inflammation and ongoing blood–brain barrier compromise. These factors collectively contribute to the emergence of white matter hyperintensities, promote amyloid pathology, and may accelerate neurodegenerative processes, including Alzheimer’s disease. This review also emphasizes the critical role of advanced imaging techniques in assessing cerebromicrovascular health and the need for targeted interventions to address these cerebrovascular complications. A deeper understanding of the cerebrovascular mechanisms of long COVID is essential to advance targeted treatments and mitigate its long-term neurocognitive consequences.

Digital cognitive training may improve cognition in people with mild cognitive impairment (MCI); however, the effect on functionality remains poorly defined. The Canadian Occupational Performance Measure (COPM) is a valid and consistent instrument for evaluating the performance of activities of daily living in this population. This study used the COPM to investigate the effects of digital cognitive training on functionality in individuals with MCI. We recruited participants aged 60 or older with MCI to a double-blinded, randomized, stepped wedge clinical trial of digital cognitive training compared to an active control group of commercial computer games. Participants were evaluated for functionality and cognition before and after 10 h of intervention. Ten hours of digital cognitive training improved functionality, measured by COPM performance, compared to the active control group. Learning over trials also improved significantly after 10 h of digital cognitive training, as compared to the active control group. Ten hours of digital cognitive training improved functionality in MCI. More sensitive tools, such as COPM, should be used to evaluate the effect of therapeutic interventions for functionality in MCI.