The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

Background: Long-term care (LTC) costs create burdens on aging societies. Maintaining oral health through dental visits may result in shorter LTC periods, thereby decreasing LTC costs; however, this remains unverified. We examined whether dental visits in the past 6 months were associated with cumulative LTC insurance (LTCI) costs.

Methods: This cohort study of the Japan Gerontological Evaluation Study targeted independent adults aged≥65 years in 2010 over an 8-year follow-up. We used data from a self-reported questionnaire and LTCI records from the municipalities. The outcome was cumulative LTCI costs, and exposure was dental visits within 6 months for prevention, treatment, and prevention or treatment. A 2-part model was used to estimate the differences in the predicted cumulative LTCI costs and 95% confidence intervals (CIs) for each dental visit.

Results: The mean age of the 8 429 participants was 73.7 years (standard deviation [SD] = 6.0), and 46.1% were men. During the follow-up period, 17.6% started using LTCI services. The mean cumulative LTCI cost was USD 4 877.0 (SD = 19 082.1). The predicted cumulative LTCI costs were lower among those had dental visits than among those who did not. The differences in predicted cumulative LTCI cost were -USD 1 089.9 (95% CI = -1 888.5 to -291.2) for dental preventive visits, -USD 806.7 (95% CI = -1 647.4 to 34.0) for treatment visits, and -USD 980.6 (95% CI = -1 835.7 to -125.5) for preventive or treatment visits.

Conclusions: Dental visits, particularly preventive visits, were associated with lower cumulative LTCI costs. Maintaining oral health through dental visits may effectively reduce LTCI costs.

Aging is the process of gradual physio-biochemical deterioration. Although aging is inevitable, healthy aging is the key to individual and communal well-being. Therefore, it is essential to understand the regulation of aging. SIN-3/Sin-3 is a unique regulatory protein that regulates aging without DNA-binding activity. It functions by establishing multiple protein interactions. To understand the functional mechanism of this transcriptional regulator, the Caenorhabditis elegans protein interactome was assessed for SIN-3 interactions. DAF-16/FOXO emerged as one of the leading contenders for SIN-3-mediated regulation of aging. This study looks at the concerted role of SIN-3 and DAF-16 proteins in lifespan regulation. Phenotypic profiling for the mutants of these genes shows the functional accord between these 2 proteins with similar functions in stress response and vital biological processes. However, there were no significant physical interactions when checked for protein-protein interaction between SIN-3 and DAF-16 proteins. C. elegans genomics and transcriptomics data also indicated the possibilities of concerted gene regulation. This genetic regulation is more likely related to SIN-3 dominance on DAF-16 function. Overall, SIN-3 and DAF-16 proteins have strong functional interactions that ensure healthy aging. The influence of SIN-3 on DAF-16-mediated stress response is one of their convergence points in longevity regulation.

Background: Gut microbiota imbalance and sarcopenia are frequently observed in older adults. Gut microbiota and their metabolites are considered risk factors contributing to the heightened risk of sarcopenia, but whether these associations are causal remains unclear.

Methods: We conducted linkage disequilibrium score regression and 2-sample Mendelian randomization (MR) methods with single-nucleotide polymorphisms sourced from large-scale genome-wide association studies as instrumental variables to examine the causal associations linking gut microbiota with their metabolites to the sarcopenia. Following the MR analysis, subsequent sensitivity analyses were conducted to reinforce the robustness and credibility of the obtained results.

Results: MR analysis yielded compelling evidence demonstrating the correlation between genetically predicted gut microbiota and metabolites and the risk of sarcopenia. The abundance of Porphyromonadaceae, Rikenellaceae, Terrisporobacter, and Victivallis was found to be associated with walking pace. Our study also found suggestive associations of 12 intestinal bacteria with appendicular lean mass, and of Streptococcaceae, Intestinibacter, Paraprevotella, Ruminococcaceae UCG009, and Sutterella with grip strength. Specifically, we identified 21 gut microbiota-derived metabolites that may be associated with the risk of sarcopenia.

Conclusions: Utilizing a 2-sample MR approach, our study elucidates the causal interplay among gut microbiota, gut microbiota-derived metabolites, and the occurrence of sarcopenia. These findings suggest that gut microbiota and metabolites may represent a potential underlying risk factor for sarcopenia, and offer the promise of novel therapeutic focal points.

The single nucleotide polymorphism (SNP)-rs6922617 in the triggering receptor expressed on myeloid cells (TREM) gene cluster is a potential risk factor for Alzheimer's disease (AD). Here, we examined whether rs6922617 is associated with AD-defining neuropathological hallmarks and memory performance. We assessed the interaction between the variant rs6922617 and levels of beta-amyloid (Aβ), tau pathology, neurodegeneration, namely amyloid-tau-neurodegeneration framework, and cognition functions in 660 healthy controls, 794 mild cognitively impaired, and 272 subjects with AD. We employed linear regression and linear mixed models to examine the association. Here we find that the SNP-rs6922617 in the TREM gene cluster is associated with a higher global amyloid-ligands positron emission tomography (Aβ-PET) burden and lower fluorodeoxyglucose positron emission tomography (FDG-PET) load. Interestingly, rs6922617 risk allele carriers exhibit a significantly reduced tau accumulation compared to the non-carriers, indicating a discrepant association with Aβ and tau pathologies. Though the participants carrying the rs6922617 risk allele do not show a correlation with poorer cognitive performance, stronger neuropathological phenotypes, and memory impairments are evident in ApoE ε4 carriers with the rs6922617 risk allele. These results support the notion that the SNP-rs6922617 in the TREM gene cluster is associated with AD-related neuropathological hallmarks, such as Aβ and FDG-mediated neurodegeneration, rather than tau accumulation. Although the direct association with memory impairment in the Alzheimer's continuum remains inconclusive, our findings suggest a potential role of rs6922617 in facilitating neuropathology hallmarks.

The biological aging of stem cells (exhaustion) is proposed to contribute to the development of a variety of age-related conditions. Despite this, little is understood about the specific mechanisms which drive this process. In this study, we assess the transcriptomic and proteomic changes in 3 different populations of mesenchymal progenitor cells from older (50-70 years) and younger (20-40 years) individuals to uncover potential mechanisms driving stem cell exhaustion in mesenchymal tissues. To do this, we harvested primary bone marrow mesenchymal stem and progenitor cells (MPCs), circulating osteoprogenitors (COP), and adipose-derived stem cells (ADSCs) from younger and older donors, with an equal number of samples from men and women. These samples underwent RNA sequencing and label-free proteomic analysis, comparing the younger samples to the older ones. There was a distinct transcriptomic phenotype in the analysis of pooled older stem cells, suggestive of suppressed proliferation and differentiation; however, these changes were not reflected in the proteome of the cells. Analyzed independently, older MPCs had a distinct phenotype in both the transcriptome and proteome consistent with altered differentiation and proliferation with a proinflammatory immune shift in older adults. COP cells showed a transcriptomic shift to proinflammatory signaling but no consistent proteomic phenotype. Similarly, ADSCs displayed transcriptomic shifts in physiologies associated with cell migration, adherence, and immune activation but no proteomic change with age. These results show that there are underlying transcriptomic changes with stem cell aging that may contribute to a decline in tissue regeneration. However, the proteome of the cells was inconsistently regulated.

Background: The combination of exposure to multiple stressors and psychological distress may contribute to the disproportionate burden of dementia risk among Black Americans. This study estimates the effect of an index of stress and psychological distress (ie, "stress burden") on cognitive function and clinically adjudicated cognitive outcomes among older Black American adults, and examines sleep as a mediator.

Methods: The sample included 204 Black adults (79% female; mean age = 64 years) from Pittsburgh, PA, USA. Stress burden comprised 3 self-reported stress and distress measures assessed in 2016: discrimination, psychological distress, and posttraumatic stress. Potential mediators included actigraphy-assessed sleep duration and efficiency from 2018. Cognitive battery and clinical adjudication in 2019 assessed cognitive function and clinically adjudicated outcomes. Causal mediation analysis estimated the direct effect between stress burden and cognitive outcomes, and indirect effects through sleep, after adjusting for sociodemographics and hypertension.

Results: Higher stress burden had a significant direct effect on lower executive functioning and visuospatial performance. However, there were no significant indirect effects (ie, mediation) by sleep disturbances on any domain of cognitive function assessed. Also, there were no significant direct or indirect effects on clinically adjudicated outcomes.

Conclusions: Multiple stressors often co-occur and may contribute to racial disparities in cognitive health. Findings suggest that higher stress burden had negative effects on functioning in executive and visuospatial domains in this community-based sample of older Black American adults. However, there was no evidence of mediation by sleep. Findings highlight the importance of continued work to identify modifiable pathways between stress burden and cognitive health disparities.

Background: Chat Generative Pre-trained Transformer (ChatGPT) and other ChatBots have emerged as tools for interacting with information in manners resembling natural human speech. Consequently, the technology is used across various disciplines, including business, education, and even in biomedical sciences. There is a need to better understand how ChatGPT can be used to advance gerontology research. Therefore, we evaluated ChatGPT responses to questions on specific topics in gerontology research, and brainstormed recommendations for its use in the field.

Methods: We conducted semistructured brainstorming sessions to identify uses of ChatGPT in gerontology research. We divided a team of multidisciplinary researchers into 4 topical groups: (a) gero-clinical science, (b) basic geroscience, (c) informatics as it relates to electronic health records, and (d) gero-technology. Each group prompted ChatGPT on a theory-, methods-, and interpretation-based question and rated responses for accuracy and completeness based on standardized scales.

Results: ChatGPT responses were rated by all groups as generally accurate. However, the completeness of responses was rated lower, except by members of the informatics group, who rated responses as highly comprehensive.

Conclusions: ChatGPT accurately depicts some major concepts in gerontological research. However, researchers have an important role in critically appraising the completeness of its responses. Having a single generalized resource like ChatGPT may help summarize the preponderance of evidence in the field to identify gaps in knowledge and promote cross-disciplinary collaboration.

Aging is associated with chronic oxidative stress, which contributes to the deterioration of the immune system, increasing morbidity and mortality. A positive social environment permits health maintenance and a slower rate of aging. Improvements in immune function and oxidative stress were shown in peritoneal leukocytes and organs of old mice and adult prematurely aging mice (PAM) after cohabitation with adults or exceptional non-prematurely aging mice (ENPAM), respectively, for 2 months, but adults and ENPAM experienced deterioration. This was solved by shortening the cohabitation time to 15 minutes per day for 2 months, where old mice and PAM maintained immune and redox state improvements in their peritoneal leukocytes, as well as a greater longevity, and adults and ENPAM did not show deterioration. However, it is unknown whether the positive effects of this short cohabitation are reflected in the immunity and redox state of the organs. The aim of the present study was to test whether a cohabitation of 15 minutes per day for 2 months maintains these positive effects in the organs of retired breeder female old mice and PAM and avoids the negative ones in adults and ENPAM. After cohabitation the animals were sacrificed, and the thymus and spleen were extracted to evaluate the immune function. The oxidative state was also analyzed in the spleen, liver, heart, lung, and kidney. The results show that after cohabitation, old mice and PAM improved their immunity and redox state, and adults and ENPAM showed no deterioration. This cohabitation can be suggested to improve health and slow down aging.

Background: Mitochondrial dysfunction manifests in neurodegenerative diseases and other age-associated disorders. In this study, we examined variation in inherited mitochondrial DNA (mtDNA) sequences in Black and White participants from 2 large aging studies to identify variants related to cognitive function.

Methods: Participants included self-reported Black and White adults aged ≥70 years in the Lifestyle Interventions and Independence for Elders (LIFE; N = 1 319) and Health Aging and Body Composition (Health ABC; N = 788) studies. Cognitive function was measured by the Digit-Symbol Substitution Test (DSST), and the Modified Mini-Mental State Examination (3MSE) at baseline and over follow-up in LIFE (3.6 years) and Health ABC (10 years). We examined the joint effects of multiple variants across 16 functional mitochondrial regions with cognitive function using a sequence kernel association test. Based on these results, we prioritized meta-analysis of common variants in Black and White participants using mixed effects models. A Bonferroni-adjusted p value of <.05 was considered statistically significant.

Results: Joint variation in subunits ND1, ND2, and ND5 of Complex I, 12S RNA, and hypervariable region (HVR) were significantly associated with DSST and 3MSE at baseline. In meta-analyses among Black participants, variant m.4216T>C, ND1 was associated with a faster decline in 3MSE, and variant m.462C>T in the HVR was associated with a slower decline in DSST. Variant m.5460G>C, ND2 was associated with slower and m.182C>T in the HVR was associated with faster decline in 3MSE in White participants.

Conclusions: Among Black and White adults, oxidative phosphorylation Complex I variants were associated with cognitive function.