GeroScience最新文献

Aging is associated with disrupted sleep patterns, such as fragmented sleep and reduced efficiency, leading to negative health outcomes. There is evidence of a bidirectional relationship between sleep and gut microbiota, which plays a key role in the gut-brain axis and overall health. However, studies on this relationship in older adults have limited generalizability and show conflicting results, highlighting the need for further research. This study aimed to investigate the associations between sleep quality and gut microbiota composition in healthy Chinese older adults using subjective and objective sleep measures to capture various aspects of sleep quality and explore potential impacts on emotional well-being and cognitive performance. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire, while objective sleep quality was measured with actigraphy. Gut microbiota sequencing was performed on stool samples. The results show a robust positive association between gut microbiota richness and objective sleep quality in older adults, independent of subjective sleep quality and demographics, lifestyle, and health covariates. However, no significant link was found between gut microbiota richness and subjective sleep quality. Specific taxa like Bacteroidetes, Ruminococcus, Collinsella, Veillonella, and Holdemania were tentatively linked to sleep quality. These findings emphasize the connection between sleep quality and gut microbiota composition in older adults with potential research and clinical implications, improving our understanding of the mechanisms underlying the sleep-gut microbiota relationship and guiding the development of interventions for improving both sleep quality and gut health in older adults.

Brain network dynamics have been extensively explored in patients with subjective cognitive decline (SCD). However, these studies are susceptible to individual differences, scanning parameters, and other confounding factors. Therefore, how to reveal subtle SCD-related subtle changes remains unclear. Cross-sectional and longitudinal resting-state functional magnetic resonance imaging data from both Chinese and Western populations were analyzed. We proposed a framework of dynamic proportional loss of functional connectivity (DPLFC). After its stability was validated, the optimal parameters were applied for the clinical diagnosis of SCD. DPLFC yielded a relatively high intraclass correlation coefficient. In particular, the DPLFC of the left superior frontal gyrus (SFG) progressively decreased along the Alzheimer's disease (AD) continuum. Compared with the traditional index, the DPLFC had better classification performance between cognitively normal controls and patients with SCD. Furthermore, DPLFC was related to Aβ deposition and scale scores. Patients with lower DPLFC values had a greater risk of cognitive decline. Decreased DPLFC in the left SFG may be a potential AD-related neuroimaging biomarker at an early stage.

Research in aging often refers to animal models, particularly C57BL/6J (B6J) mice, considered gold standard. However, B6J mice are distributed by different suppliers, which results in divers substrains exhibiting notable phenotypic differences. To ensure a suitable phenotype of cardiac aging, we performed heart analyses of young (5 months) and old B6J mice (24 months) from two substrains: B6JRj (Janvier) and B6JCrl mice (Charles River). In hearts of both substrains, myocardial fibrosis increased with age; however, only in old B6JRj mice cardiac hypertrophy associated with a decreased ejection fraction was observed. Gene set enrichment analysis in heart tissue using proteomic data revealed different age-associated pathway changes between the substrains, especially in oxidative phosphorylation. Functional assessment of isolated cardiomyocytes verified cardiac impairment during aging in B6JRj mice. Overall, results demonstrate that cardiac aging manifests as a moderate systolic dysfunction in B6JRj mice, while B6JCrl mice display no functional changes with age.

The neuromuscular junction shows several degenerative changes with aging, resulting in a reduction of transmission efficacy. These changes, paired with low-grade chronic inflammation, were considered triggers of the aging muscle processes. The main objective of this study is to assess the role of leukocyte count-derived ratios, nerve conduction velocity (NCV), and compound muscle action potential (CMAP) in determining time-dependent reduction in lower limb muscle explosive strength, a condition that has been defined as powerpenia. The InCHIANTI study enrolled a representative sample from the registry lists of two towns in Tuscany, Italy. Baseline data were collected in 1998, with follow-up visits every 3 years. For the purpose of this analysis, we used 1229 subjects and 3814 follow-up assessments. Subjects with lower values of monocyte-to-lymphocyte ratio (ML-ratio) had higher nerve conduction velocity and higher proximal and distal action potential values; moreover, considering the interaction between age for ML-ratio effect, a statistically significant direct association is found with all the electromyography-parameters. Lower limb muscle power shows a gender dimorphism, male subjects having higher values at baseline, but experiencing steeper decline rate during the follow-up, compared to females. Muscle power was inversely associated with ML-ratio, proximal CMAP, distal CMAP, and NCV. Moreover, we found a direct and statistically significant second-order interaction (age for ML-ratio), meaning that at the same age, increasing ML-ratio increases lower limb muscle power. Lastly, also body composition variation across aging is directly associated with lower limb muscle power. Reduced immunological and neurological homeostasis affects the powerpenia phenotype in a large representative sample of Italian men and women.

Inhibition of the target of rapamycin (TOR/mTOR) protein kinase by the drug rapamycin extends lifespan and health span across diverse species. However, rapamycin has potential off-target and side effects that warrant the discovery of additional TOR inhibitors. TOR was initially discovered in Saccharomyces cerevisiae (yeast) which contains two TOR paralogs, TOR1 and TOR2. Yeast lacking functional Tor1 are viable but are hypersensitive to growth inhibition by TORC1 inhibitors, which is a property of yeast that can be exploited to identify TOR inhibitors. Additionally, yeast lacking FK506-sensitive proline rotamase (FPR1) or containing a tor1-1 allele (a mutation in the Fpr1-rapamycin binding domain of Tor1) are robustly and selectively resistant to rapamycin and analogs that allosterically inhibit TOR activity via an FPR1-dependent mechanism. To facilitate the identification of TOR inhibitors, we generated a panel of yeast strains with mutations in TOR pathway genes combined with the removal of 12 additional genes involved in drug efflux. This creates a drug-sensitive strain background that can sensitively and effectively identify TOR inhibitors. In a wild-type yeast strain background, 25 µM of Torin1 and 100 µM of GSK2126458 (omipalisib) are necessary to observe TOR1-dependent growth inhibition by these known TOR inhibitors. In contrast, 100 nM Torin1 and 500 nM GSK2126458 (omipalisib) are sufficient to identify TOR1-dependent growth inhibition in the drug-sensitized background. This represents a 200-fold and 250-fold increase in detection sensitivity for Torin1 and GSK2126458, respectively. Additionally, for the TOR inhibitor AZD8055, the drug-sensitive system resolves that the compound results in TOR1-dependent growth sensitivity at 100 µM, whereas no growth inhibition is observed in a wild-type yeast strain background. Our platform also identifies the caffeine analog aminophylline as a TOR1-dependent growth inhibitor via selective tor1 growth sensitivity. We also tested nebivolol, isoliquiritigenin, canagliflozin, withaferin A, ganoderic acid A, and taurine and found no evidence for TOR inhibition using our yeast growth-based model. Our results demonstrate that this system is highly effective at identifying compounds that inhibit the TOR pathway. It offers a rapid, cost-efficient, and sensitive tool for drug discovery, with the potential to expedite the identification of new TOR inhibitors that could serve as geroprotective and/or anti-cancer agents.

Aging is a multi-organ disease, yet the traditional approach has been to study each organ in isolation. Such organ-specific studies have provided invaluable information regarding its pathomechanisms. However, an overall picture of the whole-body network (WBN) during aging is still incomplete. In this study, we analyzed the functional magnetic resonance imaging blood-oxygen level-dependent, respiratory rate and heart rate time series of a young and an elderly group during eyes-open resting-state. We constructed WBNs by exploring the time-lagged coupling between the different organs. First, we showed that our analytical pipeline could identify regional differences in the networks of both cohorts, allowing us to proceed with the remaining analyses. The comparison of the WBNs revealed a complex relationship where some connections were stronger and some weaker in the elderly. Finally, the interconnectivity and segregation of the WBNs were negatively correlated with the short-term memory and verbal learning of the young participants. This study: i) validated our methodology, ii) identified differences in the WBNs of the two groups and iii) showed correlations of WBNs with behavioral measures. In conclusion, the concept of WBN shows great potential for the understanding of aging and age-related diseases.

Arthritis, a chronic inflammatory condition linked to cardiovascular disease (CVD) and bone fracture, is more frequent among military veterans and postmenopausal women. This study examined correlates of arthritis and relationships of arthritis with risks of developing CVD, bone fractures, and mortality among postmenopausal veteran and non-veteran women. We analyzed longitudinal data on 135,790 (3,436 veteran and 132,354 non-veteran) postmenopausal women from the Women’s Health Initiative who were followed-up for an average of 16 years between enrollment (1993–1998) and February 17, 2024. Regression and multistate Markov modeling were applied to meet study objectives. The prevalence of arthritis at enrollment (1993–1998) did not differ by veteran status in a fully adjusted logistic model. Variable selection yielded 5 key predictors of prevalent arthritis among veterans and 15 key predictors among non-veterans. In fully-adjusted Cox models, prevalent arthritis was associated with CVD (hazard ratio [HR] = 1.08, 95% confidence interval [CI]: 1.05, 1.10) and all-cause mortality (HR = 1.03, 95% CI: 1.01, 1.05) risks among non-veterans only, but was not associated with bone fracture risk irrespective of veteran status. Transition probabilities between health and CVD and between bone fracture and death were higher among women with vs. without arthritis. The latter transition was more strongly related to arthritis among non-veteran vs. veteran women. In conclusion, among postmenopausal women, prevalent arthritis was associated with greater probabilities of transitioning from a healthy state to CVD and from bone fracture to death, with worse prognosis after bone fracture among those who did not serve in the military.

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is frequently associated with musculoskeletal complications, including sarcopenia and osteoporosis, which substantially impair patient quality of life. Despite these clinical observations, the molecular mechanisms linking AD to bone loss remain insufficiently explored. In this study, we examined the femoral bone microarchitecture and transcriptomic profiles of APP/PS1 transgenic mouse models of AD to elucidate the disease’s impact on bone pathology and identify potential gene candidates associated with bone deterioration. We performed micro-computed tomography (microCT) and RNA transcriptome analysis on the femoral bone of these mice. We observed a significant reduction in bone microstructure in both male and female APP/PS1 mice compared to their wild-type counterparts. Transcriptomic analysis of femoral bone tissue revealed substantial differential gene expression between AD mice and controls. Specifically, APP/PS1 mice exhibited differential expression in 289 protein-coding genes across both sexes. Notably, in female APP/PS1 mice, 664 genes were differentially expressed, with key genes such as Shh, Efemp1, Arg1, EphA2, Irx1, and PORCN potentially implicated in bone loss. In male APP/PS1 mice, 787 genes were differentially expressed, with Sel1l, Ffar4, Hspa1a, AMH, WFS1, and CLIC1 emerging as notable candidates in the context of bone deterioration. Gene Ontology (GO) enrichment analysis further revealed distinct sex-specific gene pathways between male and female APP/PS1 mice, underscoring the differential molecular underpinnings of bone pathology in AD. This study identifies novel sex-specific genes in the APP/PS1 mouse model and proposes potential therapeutic targets to mitigate bone loss in AD patients.

A healthy diet is a key determinant of successful aging. However, the psychological, social, and physiological changes associated with ageing often disrupt dietary behaviours. Hungary has one of the highest rates of chronic age-related diseases in the European Union, exacerbated by unhealthy dietary patterns and rapid population aging. This study evaluates attitudes and barriers to healthy eating among older adults in a socioeconomically disadvantaged region of Hungary, identifying determinants of these attitudes across different age groups. A cross-sectional survey sampled 678 adults aged 18 and older from Northeast Hungary, assessing their beliefs on healthy eating through an attitude score (range: 9–45). Multivariate regression analyses were conducted to explore relationships between mental health, self-perceived health, and attitudes toward healthy eating. The mean attitude score was 31.47 (± 5.14), with older adults (≥ 65 years) showing significantly greater uncertainty about dietary choices. The cost of healthy food was the most frequently reported barrier, regardless of age. Regression results revealed that older adults with higher well-being (B = 0.03, p = 0.026), life satisfaction (B = 0.40, p = 0.005), and self-perceived health (fair: B = 2.20, p = 0.003; good/very good: B = 1.96, p = 0.031) were more likely to have positive attitudes toward healthy eating. These results emphasize the importance of addressing both mental and physical health in educational interventions to promote healthier diets. Tailored approaches addressing affordability and accessibility of healthy foods are critical to advancing Hungary’s National Healthy Aging Program and mitigating dietary risk factors among vulnerable populations.

Rapamycin, also known as sirolimus, has demonstrated great potential for application in longevity medicine. However, the dynamics of low-dose rapamycin bioavailability, and any differences in bioavailability for different formulations (e.g., compounded or commercial), remain poorly understood. We thus explored rapamycin bioavailability in two real-world cohorts to begin providing a foundational understanding of differences in effects between formulations over time. The small trial study cohort was utilized to explore the blood rapamycin levels of commercial (n = 44, dosages 2, 3, 6, or 8 mg) or compounded (n = 23, dosages 5, 10, or 15 mg) rapamycin 24 h after dose self-administration. Results suggested dose-to-blood level relationships were linear for both formulations, though compounded had a lower bioavailability per milligram of rapamycin (estimated to be 31.03% of the same dose of commercial). While substantial inter-individual heterogeneity in blood rapamycin levels was observed for both formulations, repeat tests for individuals over time demonstrated relative consistency. Extending exploration to 316 real-world longevity rapamycin users from the AgelessRx Observational Research Database produced similar findings, and additionally suggested that blood rapamycin levels peak after 2 days with gradual decline thereafter. Taken together, our findings suggest that individualized dosing and routine monitoring of blood rapamycin levels should be utilized to ensure optimal dosing and efficacy for healthy longevity.