Experimental gerontology最新文献

Aging is an inevitable and gradual decline in several biological functions. Mitochondrial dysfunction is one of the most important hallmarks of aging. In this context, alterations in metabolites associated with mitochondrial dysfunction may serve as a significant biomarker. This study aimed to investigate the existence of a relationship between the key metabolites involved in bioenergetics metabolism and aging. 53 volunteers ranged 20–85 years participated in the study. We tested the association between different tricarboxylic acid (TCA) cycle metabolites, fatty acid metabolism, and amino acid metabolism with age, sex, body composition, and proxy markers of aging such as walking speed, grip strength and chair test. We found that lactic acid negatively correlated with age while several fatty acid metabolites, such as azelaic, sebacic, and linoleic acids, showed positive correlations with age (p < 0.05). Sex-specific trends, such as glycerol, and dodecanoic acid, were also observed for certain metabolites. Furthermore, citric acid levels were found to have a significant association with physical function and body composition measures. Participants with higher citric acid levels displayed improved performance in physical tests and favorable body composition indices. Additionally, fumaric acid and adipic acid showed positive correlations with fat-free body mass, while sebacic acid was negatively associated with measures of fat mass. These findings underscore the importance of understanding the role of circulating bioenergetics metabolites with age, sex variations, and their potential implications in body composition and physical performance.

Background

Cerebral small vessel disease (CSVD) closely correlates to cognitive impairment, but its pathophysiology and the neurovascular mechanisms of cognitive deficits were unclear. We aimed to explore the dysfunctional patterns of neurovascular coupling (NVC) in patients with CSVD and further investigate the neurovascular mechanisms of CSVD-related cognitive impairment.

Methods

Forty-three patients with CSVD and twenty-four healthy controls were recruited. We adopted resting-state functional magnetic resonance imaging combined with arterial spin labeling to investigate the NVC dysfunctional patterns in patients with CSVD. The Human Brain Atlas with 246 brain regions was applied to extract the NVC coefficients for each brain region. Partial correlation analysis and mediation analysis were used to explore the relationship between CSVD pathological features, NVC dysfunctional patterns, and cognitive decline.

Results

8 brain regions with NVC dysfunction were found in patients with CSVD (p < 0.025, Bonferroni correction). The NVC dysfunctional patterns in regions of the default mode network and subcortical nuclei were negatively associated with lacunes, white matter hyperintensities burden, and the severity of CSVD (FDR correction, q < 0.05). The NVC decoupling in regions located in the default mode network positively correlated with delayed recall deficits (FDR correction, q < 0.05). Mediation analysis suggested that the decreased NVC pattern of the left superior frontal gyrus partially mediated the impact of white matter hyperintensities on delayed recall (Mediation effect: -0.119; 95%CI: −11.604,-0.458; p < 0.05).

Conclusion

The findings of this study reveal the NVC dysfunctional pattern in patients with CSVD and illustrate the neurovascular mechanism of CSVD-related cognitive impairment. The NVC function in the left superior frontal gyrus may serve as a promising biomarker and therapeutic target for memory deficits in patients with CSVD.

The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein. In addition, Peroxyredoxin 3 (PRXIII) protein decreased by 50 %, which on overall suggested the absence of induction of mitochondrial biogenesis by RSV in old Sol. A novel direct correlation between PGC-1α and PRXIII proteins was demonstrated by correlation analysis in RSV and ad-libitum (AL) rats, supporting the reciprocally coordinated expression of the proteins. RSV supplementation led to an unexpected 50 % increase in the frequency of the oxidized base OH8dG in mtDNA. Furthermore, RSV supplementation induced a 50 % increase in the DRP1 protein of mitochondrial dynamics. In both rat groups an inverse correlation between PGC-1α and the frequency of OH8dG as well as an inverse correlation between PRXIII and the frequency of OH8dG were also found, suggestive of a relationship between oxidative damage to mtDNA and mitochondrial biogenesis activity. Such results may indicate that the antioxidant activity of RSV in aged Sol impinged on the oxidative fiber-specific, ROS-mediated, retrograde communication, thereby affecting the expression of SIRT1, PGC-1α and PRXIII, reducing the compensatory responses to the age-related mitochondrial oxidative stress and decline.

Background

Neurotransmitter transport disorders may play a crucial role in Parkinson's Disease (PD), and Solute carrier family 6 member 12 (SLC6A12) encodes a neurotransmitter transporter. However, the relationship between SLC6A12 and PD remains largely unexplored.

Methods

We utilized the GEO database (107 samples) and clinical data (80 samples) to investigate the role of SLC6A12 in PD through differential expression analysis, ROC analysis, and RT-qPCR experiments. Subsequently, in vitro model, axon length measurement, CCK8 assay, flow cytometry, and JC-1 assays were conducted. Additionally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein-protein interaction (PPI) network, gene set enrichment analysis (GSEA), and western blot experiments were assessed to explore the functional and mechanistic pathways of SLC6A12 in PD. Finally, CIBERSORT analysis was performed to investigate the correlation between SLC6A12 and immune cells in PD.

Results

The expression of SLC6A12 was significantly higher in individuals with PD compared to healthy controls. Inhibiting SLC6A12 expression in PD models enhanced neuronal growth and proliferation activity while reducing cell apoptosis. Furthermore, SLC6A12 was found to be involved in neuronal development, synaptic function, and neural protein transport processes in PD, potentially regulating the MAPK signaling pathway through the Ras/Raf/MEK/ERK axis, contributing to the pathological process of PD. Additionally, SLC6A12 was implicated in immune environment disturbances in PD, notably affecting CD4 T cell expression.

Conclusion

This study documented the pathogenicity of SLC6A12 in PD for the first time, expanding the understanding of its molecular function and providing a potential target for precise treatment of PD.

Background

The role of interleukins in sarcopenia development has been acknowledged, yet the specifics of their involvement remain to be fully understood. This study aimed to explore alterations in interleukin levels among sarcopenia patients.

Methods

Searches were conducted in Embase, Medline, and the Cochrane Library for literature published up to May 2023. Eligible observational studies with a diagnosis of sarcopenia were included. The Newcastle–Ottawa Scale was utilized for quality assessment. For data synthesis, a random-effects model was used, and the Mantel–Haenszel method was used for pooled estimates.

Results

Of the 7685 articles screened, 37 met the inclusion criteria. Statistically significant differences in the levels of IL-1β, IL-6 and IL-10 were detected in sarcopenia patients. Specifically, IL-1β (95 % CI: 0.33 [0.12, 0.54], P < 0.05), IL-6 (95 % CI: 0.91 [0.59, 1.24], P < 0.05), and IL-10 (95 % CI: 0.11 [0.07,0.15], P < 0.05) were detected. However, no significant associations were found between serum IL-4 (95 % CI: 0.36 [−0.18, 0.42], P = 0.44), IL-8 (95 % CI: −1.05 [−3.06, 0.95], P = 0.3), IL-12 (95 % CI: −3.92 [−8.32,0.48], P = 0.08) or IL-17 (95 % CI: 0.22 [−2.43, 2.88], P = 0.87) and sarcopenia. Subgroup analysis showed no significant difference in IL-6 (95 % CI: −0.03 [−0.72, 0.66], P = 0.93) and IL-10 (95 % CI: 0.1 [−0.44, 0.64], P = 0.72) among patients with European standard sarcopenia.

Conclusions

Inflammation plays a role in sarcopenia, and the serum levels of IL-1β, IL-6, and IL-10 are associated with sarcopenia. Further research is needed to clarify these associations.

Clinical Trials Registration Number: CRD42024506656.

Background

Neuroinflammation is closely related to Alzheimer's Disease (AD) pathology, hence supplements with anti-inflammatory property could help attenuate the progression of AD. This study was conducted to evaluate the potential anti-inflammatory effects of liposome encapsulated thymol (LET), administered orally, in prevention of Alzheimer in a rat model by anti-inflammatory mechanisms.

Methods

The rats were grouped into six groups (n = 10 animals per group), including Control healthy (Con), Alzheimer's disease (AD) model, AD model treated with free thymol in 40 and 80 mg/kg body weight (TH40 and TH80), AD model treated with LET in 40 and 80 mg/kg of body weight (LET40 and LET80). The behavioral response of step through latency (Passive Avoidance Test), concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) were assessed in serum and hippocampus.

Results

The results showed that significant increase in concentrations of IL-1β (P = 0.001), IL-6 (P = 0.001), TNF-α (P = 0.001) and COX-2 (P = 0.001) in AD group compared with healthy control rats. AD induction significantly reduced step through latency and revealed deficits in passive avoidance performance. The results also showed the treatment with free thymol especially in higher concentrations and also LTE could decrease serum concentrations of IL-1β (P < 0.05), IL-6 (P < 0.05), TNF-α (P < 0.05), and COX-2 (P < 0.05) and increase BDNF (P < 0.05) compared with control Alzheimer rats in hippocampus and serum. There were also significant correlations between serum and hippocampus concentrations of IL-1β (r² = 0.369, P = 0.001), IL-6 (r² = 0.386, P = 0.001), TNF-α (r² = 0.412, P = 0.001), and COX-2 (r² = 0.357, P = 0.001). It means a closed and positive relation between serum and hippocampus concentrations of IL-1β, IL-6, TNF-α, and COX-2.

Conclusions

LET demonstrates its ability to attenuate neuroinflammatory reaction in AD model through suppression of IL-1β, IL-6, and TNF-α and COX-2 indicators. Hence, it can ameliorate AD pathogenesis by declining inflammatory reaction.

Background

Vascular dementia (VaD), the second most prevalent type of dementia, lacks a well-defined cause and effective treatment. Our objective was to utilize bioinformatics analysis to discover the fundamental disease-causing genes and pathological mechanisms in individuals diagnosed with VaD.

Methods

To identify potential pathogenic genes associated with VaD, we conducted weighted gene co-expression network analysis (WGCNA), differential expression analysis, and protein–protein interaction (PPI) analysis. The exploration of potential biological mechanisms involved the utilization of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Moreover, a bilateral common carotid artery stenosis (BCAS) mouse model of VaD was established, and the expression of the hub gene, its relationship with cognitive function and its potential pathogenic mechanism were verified by cognitive behavior tests, cerebral blood flow measurement, Western blotting, and immunofluorescence experiments.

Results

This study identified 293 DEGs from the brain cortex of VaD patients and healthy controls, among these genes, the Toll-like receptor 2 (TLR2) gene was identified as hub gene, and it was associated with the apoptosis-related pathway PI3K/AKT.The BCAS model demonstrated that the use of TLR2 inhibitors greatly enhanced the cognitive function of the mice (p < 0.05). Additionally, there was a notable decrease in the number of apoptotic cells in the brain cortex of the mice (p < 0.01). Moreover, significant alterations in the levels of proteins related to the PI3K/AKT pathway and cleaved-caspase3 proteins were detected (p < 0.05).

Conclusions

TLR2 plays a role in the pathophysiology of VaD by enhancing the neuronal apoptotic pathway, suggesting it could be a promising therapeutic target.

Purpose

Ageing is associated with cognitive decline. This study investigated the individual and combined effects of resistance exercise (RE) and whey protein supplementation (PRO) on cognitive function in older men.

Methods

In a pooled-groups analysis, 36 older men (age: 67 ± 4 years) were randomised to either RE (2 x/week; n = 18) or no exercise (NE; n = 18), and either PRO (2 × 25 g/d whey protein isolate; n = 18) or control (CON, 2 × 23.75 g maltodextrin/d; n = 18). A sub-analysis was also conducted between RE + CON (n = 9) and RE + PRO (n = 9). At baseline and 12 weeks, participants completed a battery of neuropsychological tests (CANTAB; Cambridge Cognition, UK) and neurobiological, inflammatory, salivary cortisol and insulin sensitivity biomarkers were quantified.

Results

PRO improved executive function z-score (+0.31 ± 0.08) greater than CON (+0.06 ± 0.08, P = 0.03) and there was a trend towards improved global cognitive function (P = 0.053). RE and RE + PRO did not improve any cognitive function domains (p ≥ 0.07). RE decreased tumor necrosis factor-alpha (P = 0.02) and interleukin-6 (P = 0.048) concentrations compared to NE, but changes in biomarkers did not correlate with changes in cognitive domains. Muscle strength (r = 0.34, P = 0.045) and physical function (ρ = 0.35–0.51, P < 0.05) outcomes positively correlated with cognitive function domains at baseline, but only Δskeletal muscle index correlated with Δepisodic memory (r = 0.34, P = 0.046) following the intervention.

Conclusion

In older men, PRO improved cognitive function, most notably executive functioning. RE did not improve any cognitive function domains but did decrease biomarkers of systemic inflammation. No synergistic effects were observed.

Objectives

As populations age globally, understanding the dynamics that influence the well-being of older individuals become increasingly crucial. The research employs a comprehensive approach to unravel the multifaceted interplay between social engagements and subjective health perceptions of older Indians, with a special focus on gender differences.

Subjects and methods

This study used data from the Longitudinal Aging Study in India (LASI) wave 1, 2017–18 with a total sample of 30,533 older adults aged 60 years and above. Bivariate analysis, chi-square tests and unadjusted and adjusted average marginal effects from logistic regression models were used to assess the relationship between social engagements and subjective health among older adults, stratified by gender.

Results

The prevalence of poor health status decreased with higher frequency of social networks among both men (pp. (percentage point) = 6.1; CI (Confidence Interval): 10.6, 1.6) and women (pp. = 9.2; CI: 14.9, 3.4). The adjusted average marginal effects demonstrate that with an increase in the overall score of social engagement, the likelihood of poor health is almost reduced by half. For men, the prevalence of poor health was 9.8 pp. (95 % CI: 13.7, 5.8), while for women, it was 9.3 pp. (95 % CI: 15.2, 3.1).

Conclusion

Gendered perspectives unveil unique patterns, highlighting how societal expectations and roles assigned to each gender may influence the subjective health perceptions of older individuals. This study adds to the expanding knowledge base to enhance the well-being and fulfillment of aging populations, considering the complex interplay of social dynamics and gendered perspectives.

The present study aimed to compare V̇O₂max (absolute, adjusted to total body mass, and adjusted to lean mass) in recreational runners and sedentary women < and > 50 yr and verify the effect of aging and physical activity level on the three types of V̇O₂ max expression. The study included 147 women:85 runners (45.7 ± 14.1 yr) and 62 sedentary controls (48.8 ± 9.8 yr). They were subjected to cardiopulmonary exercise testing for V̇O₂ max measurement and a body composition test by dual-emission X-ray absorptiometry system. V̇O₂max were expressed as absolute values (L/min), relative to total body mass values (mL/kg/min), and relative to lean mass values (mL/kgLM/min). The two-way analysis of variance revealed a significant interaction [F(2,131) = 4.43, p < 0.001] and effects of age group [F(2,131) = 32.79, p < 0.001] and physical activity group [F(2,131) = 55.64, p < 0.001] on V̇O₂max (mL/min). V̇O₂max (mL/kg/min) and V̇O₂ max (mL/kgLM/min) were significantly influenced by age and physical activity levels. The multiple regression model explains 76.2 % of the dependent variable V̇O₂max (mL/kg/min), age (β = −0.335, t = −7.841, p < 0.001), and physical activity group (β = −0.784, t = −18.351, p < 0.001). In conclusion, female runners had higher V̇O₂ max values than sedentary women at all ages, even though aging has a greater impact on V̇O₂ max in the runners group. In addition to cardiorespiratory fitness, women's metabolic lean mass function, as measured by V̇O₂max adjusted by lean mass, is significantly influenced by aging. Finally, physical activity has a greater impact on V̇O₂ max levels than aging.