Gerontology最新文献

Introduction: The longevity is influenced by genetic, environmental, and lifestyle factors. The specific changes that occur in the gut microbiome during the aging process, and their relationship to longevity and immune function, have not yet been fully understood. The ongoing research of other microbiome based on longevity cohort in Kazakhstan provides preliminary information on longevity-related aging, where cytokine expression is associated with specific microbial communities and microbial functions.

Methods: Metagenomic shotgun sequencing study of 40 long-lived individuals aged 90 years and over was carried out, who were conditionally healthy and active, able to serve themselves, without a history of serious infection and cancer, who had not taken any antimicrobials, including probiotics. Blood serum was analyzed for clinical and laboratory characteristics. The cytokine and chemokine profile in serum and stool samples was assessed using multiplex analysis.

Results: We found a significant increase in the expression of pro-inflammatory cytokines IL-1a, IL-6, 12p70, IP-10, IFNα2, IL-15, TNFa, as well as chemokines MIP-1a/CCL3 and MIP-1b/CCL4, chemokine motif ligands MCP-3/CCL7 and MDC/CCL22(1c). Nonagenerians and centenarians demonstrated a greater diversity of core microbiota genera and showed an elevated prevalence of the genera Bacteroides, Clostridium, Escherichia, and Alistipes. Conversely, there was a decrease in the abundance of the genera Ruminococcus, Fusicatenibacter, Dorea, as well as the species Fusicatenibacter saccharivorans. Furthermore, functional analysis revealed that the microbiome in long-lived group has a high capacity for lipid metabolism, amino acid degradation, and potential signs of chronic inflammatory status.

Conclusion: Long-lived individuals exhibit an immune system imbalance and observed changes in the composition of the gut microbiota at the genus level between to the two age-groups. Age-related changes in the gut microbiome, metabolic functions of the microbial community, and chronic inflammation all contribute to immunosenescence. In turn, the inflammatory state and microbial composition of the gut is related to nutritional status.

Introduction: Although frailty is a geriatric syndrome that is associated with disability, hospitalization, and mortality, it can be reversible and preventable with the appropriate interventions. Additionally, as the current diagnostic criteria for frailty include only physical, psychological, cognitive, and social measurements, there is a need for promising blood-based molecular biomarkers to aid in the diagnosis of frailty.

Methods: To identify candidate blood-based biomarkers that can enhance current diagnosis of frailty, we conducted a comprehensive analysis of clinical data, messenger RNA-sequencing (RNA-seq), and aging-related factors using a total of 104 older adults aged 65-90 years (61 frail subjects and 43 robust subjects) in a cross-sectional case-control study.

Results: We identified two candidate biomarkers of frailty from the clinical data analysis, nine from the RNA-seq analysis, and six from the aging-related factors analysis. By using combinations of the candidate biomarkers and clinical information, we constructed risk prediction models. The best models used combinations that included skeletal muscle mass index measured by dual-energy X-ray absorptiometry (adjusted p = 0.026), GDF15 (adjusted p = 1.46E-03), adiponectin (adjusted p = 0.012), CXCL9 (adjusted p = 0.011), or apelin (adjusted p = 0.020) as the biomarker. These models achieved a high area under the curve of 0.95 in an independent validation cohort (95% confidence interval: 0.79-0.97). Our risk prediction models showed significantly higher areas under the curve than did models constructed using only basic clinical information (Welch's t test p < 0.001).

Conclusion: All five biomarkers showed statistically significant correlations with components of the frailty diagnostic criteria. We discovered several potential biomarkers for the diagnosis of frailty. Further refinement may lead to their future clinical use.

Introduction: Given the known female disadvantage in physical and mental health, this study aimed to investigate sex differences in self-rated health (SRH) among older adults, considering the longitudinal course by age, birth cohort, and educational level.

Methods: Data from birth cohort 1911-1937 with baseline age 55-81 years (n = 3,107) and birth cohort 1938-1947 with baseline age 55-65 years (n = 1,002) from the Longitudinal Aging Study Amsterdam (LASA) were used. Mixed model analyses were used to examine sex differences in SRH (RAND General Health Perception Questionnaire [RAND-GHPQ], range 0-16) over the age course, testing for effect modification by the birth cohort and educational level (low, middle, high).

Results: For both sexes, a decline in SRH was seen with increasing age. Over the age course, there was no significant sex difference in SRH within the older (1911-1937) birth cohort (0.13 lower score on SRH for women compared to men, 95% CI: -0.35 to 0.09) and only a small sex difference in the more recent (1938-1947) birth cohort (0.35 lower score on SRH for women compared to men [95% CI: -0.69 to -0.02], p = 0.04). There was no significant cohort difference in the size of the sex difference (p = 0.279). Those with a higher level of education reported a higher SRH, but between educational levels, there was no significant difference in the size of the sex difference in SRH.

Discussion: In this study, no relevant sex difference in SRH over the age course was observed among older adults. Future research on SRH trajectories by sex during aging should take health-related, cognitive, psychosocial, and behavioral factors into account.

Introduction: The effects of exposure to particulate matter and frailty, as well as its exposure-response relationship, have not been effectively explored. This study aimed to explore the association between long-term exposure to particulate matter and frailty state and each dimension in Chinese middle-aged and older adults, in addition to the exposure-response relationship.

Methods: The data were obtained from the National Urban Air Quality Real-Time Dissemination Platform and China Health and Retirement Longitudinal Study (CHARLS). Frailty was measured by a frailty index containing 39 indicators. Annual averages of seven pollutants were calculated from hourly monitoring data. We used multilevel regression modeling to explore the association between long-term exposure to particulate matter and frailty. Meanwhile, we explored the exposure-response relationship based on a multilevel generalized summation model. We performed a sensitivity analysis using a multi-pollution model and a quantile-based g-computation (QGC) model.

Results: A total of 15,611 participants were included in the analysis. We find that long-term exposure to PM2.5 was associated with an increased risk of pre-frailty and frailty (all p < 0.05). PMc and PM10 exhibited similar associations. The exposure-response relationship between PM2.5 showed a linear relationship, whereas the exposure-response relationship between PM10, PMc showed a nonlinear relationship. Elevated PM2.5 concentrations showed significant positive associations with the number of chronic disease score, IADL score, and functional limitation status score (all p < 0.05). PM10 and PMc showed similar positive correlations. These results remained robust after sensitivity analyses using a multi-pollution model and QGC model.

Conclusion: Chronic exposure to particulate matter was significantly associated with increased risk of frailty. The exposure-response relationship between PM2.5 concentration and frailty showed a linear relationship, and the exposure-response relationship between PM10 and PMc showed a nonlinear relationship. Exposure to a mixture of pollutants carried a higher risk of frailty than exposure to a single pollutant.

Introduction: Hip fractures can have a significant impact on the lives of older people and their families. We conducted a pragmatic randomized controlled trial of post-discharge comprehensive geriatric care (CGC) for community-dwelling older adults after a surgically repaired hip fracture. The objective of this study was to conduct a secondary analysis to compare changes in health status and perceived capability from baseline to 12 months after randomization with: the EuroQol 5-Dimension (EQ-5D-5L) (1) utility score and (2) visual analog scale (VAS); and (3) well-being as measured by participants' perceptions of their ability (or capability) toward completing life activities using the ICEpop Capability Measure for Older People (ICECAP-O).

Methods: We tested the effect of usual care (control) versus usual care and an outpatient CGC clinic (intervention) on mobility after hip fracture in community-dwelling older adults (65 years+). In this secondary analysis, we report the following outcomes: EQ-5D-5L utility score and VAS collected monthly via telephone and ICECAP-O collected in person three times at baseline, 6 months, and 12 months. Data were analyzed using area under the curve and regression adjusted for baseline values for utility scores and capability, and constrained longitudinal data analysis for VAS.

Results: We enrolled 53 older adults, including 34 women and 19 men, with mean (SD) age of 80 (8) years. There were no statistical or clinically meaningful differences between groups (control group - intervention group values) for all variables: utility score = -0.028 (95% CI: -0.071, 0.014; p = 0.18); VAS: -0.03 (95% CI: -0.39 to 0.33; p = 0.86); and capability = -0.021 (95% CI: -0.090, 0.046; p = 0.54).

Conclusions: There were no differences in outcomes between groups over 12 months, but values remained constant, contrary to a potential decline for this age group, especially after a major life event like a hip fracture.

Introduction: Current cognitive assessments suffer from floor/ceiling and practice effects, poor psychometric performance in mild cases, and repeated assessment effects. This study explores the use of digital speech analysis as an alternative tool for determining cognitive impairment. The study specifically focuses on identifying the digital speech biomarkers associated with cognitive impairment and its severity.

Methods: We recruited older adults with varying cognitive health. Their speech data, recorded via a wearable microphone during the reading aloud of a standard passage, were processed to derive digital biomarkers such as timing, pitch, and loudness. Cohen's d effect size highlighted group differences, and correlations were drawn to the Montreal Cognitive Assessment (MoCA). A stepwise approach using a Random Forest model was implemented to distinguish cognitive states using speech data and predict MoCA scores based on highly correlated features.

Results: The study comprised 59 participants, with 36 demonstrating cognitive impairment and 23 serving as cognitively intact controls. Among all assessed parameters, similarity, as determined by Dynamic Time Warping (DTW), exhibited the most substantial positive correlation (rho = 0.529, p < 0.001), while timing parameters, specifically the ratio of extra words, revealed the strongest negative correlation (rho = -0.441, p < 0.001) with MoCA scores. Optimal discriminative performance was achieved with a combination of four speech parameters: total pause time, speech-to-pause ratio, similarity via DTW, and intelligibility via DTW. Precision and balanced accuracy scores were found to be 88.1 ± 1.2% and 76.3 ± 1.3%, respectively.

Discussion: Our research proposes that reading-derived speech data facilitates the differentiation between cognitively impaired individuals and cognitively intact, age-matched older adults. Specifically, parameters based on timing and similarity within speech data provide an effective gauge of cognitive impairment severity. These results suggest speech analysis as a viable digital biomarker for early detection and monitoring of cognitive impairment, offering novel approaches in dementia care.

Introduction: The data are limited for the association between osteoarthritis (OA) and cardiovascular disease (CVD) in community-based older populations and whether there is sex difference. This study aimed to examine the relationship between OA and prevalence and incidence of CVD over 10 years in community-dwelling older adults.

Methods: Data on self-reported OA, high cholesterol, hypertension, and type 2 diabetes were collected from 1,025 community-dwelling participants aged 70-90 years in the Sydney Memory and Ageing Study. The presence of CVD at baseline was defined as self-reported presence of stroke, heart attack, transient ischaemic attack, angina, aortic aneurysm, or claudication. The incidence of CVD was defined by a combination of incident self-reported CVD or CVD mortality at different follow-up timepoints over 10 years.

Results: At baseline, 395 (38.5%) participants self-reported OA (252 [44.6%] women, 143 [31.1%] men). Self-reported OA was associated with increased prevalence of CVD in women (OR 1.67, 95% CI 1.12-2.47) but not men (1.26, 0.80-1.98). In the total population, self-reported OA at baseline was associated with increased incidence of CVD at 4 years (OR 1.77, 95% CI 1.10-2.83), 6 years (1.59, 1.03-2.46), 8 years (1.56, 1.02-2.38), and 10 years (1.66, 1.10-2.50), but not at 2 years (1.43, 0.79-2.57). Significant associations were observed in female participants at 4, 8, and 10 years, with no significant associations seen in male participants.

Conclusion: OA was associated with increased prevalence at baseline and incidence of CVD over 10 years in community-based older adults, especially women. Identifying those with OA to target their cardiovascular risk factors while managing their OA has the potential to reduce the burden of CVD in older people, particularly women.

Introduction: The aim of this study was to examine the incidence and progression of foot osteoarthritis (OA), as well as associated factors, in a community-based cohort.

Methods: Baseline (2013-2015) and follow-up (2016-2018) foot radiographs were available for 541 participants (71% women, mean age 69 years; 35% black, 53% with obesity). The LaTrobe Foot Atlas was used to examine osteophytes (OPs, score 0-3) and joint space narrowing (JSN, score 0-3) at 5 joint sites. Incident foot radiographic OA (rOA) was a baseline score <2 OP and JSN in all 5 joints with ≥2 OP or JSN at follow-up in any of the joints. Progression was a worsening OP or JSN score in a joint with baseline foot rOA. At baseline and follow-up, participants reported the presence/absence of foot symptoms and completed the Foot and Ankle Outcome Score (FAOS) for each foot. Joint-based logistic regression models with generalized estimating equations were used to examine associations (adjusted odds ratio [aOR], 95% confidence interval [CI]) of foot rOA incidence and progression and with covariates.

Results: Among 928 feet without baseline rOA, 4% developed incident foot rOA (2% of those developed symptoms). Among 154 feet with baseline foot rOA, 55% had radiographic progression (16% of those had symptoms). Women and those with higher body mass index (BMI) were more likely to have incident foot rOA (aOR [95% CI] = 4.10 [1.22, 13.8] and 1.60 [1.31, 1.97], respectively); history of gout was associated with incidence or progression of foot rOA (2.75 [1.24, 6.07]). BMI was associated with worse scores on all FAOS subscales (aORs range 1.21-1.40).

Conclusion: Progression of foot rOA is common but not necessarily related to worsening symptoms. BMI may be a modifiable risk factor for foot OA.

Background: As the largest organ in the human body, the skin is continuously exposed to intrinsic and extrinsic stimuli that impact its functionality and morphology with aging. Skin aging entails dysregulation of skin cells and loss, fragmentation, or fragility of extracellular matrix fibers that are manifested macroscopically by wrinkling, laxity, and pigmentary abnormalities. Age-related skin changes are the focus of many surgical and nonsurgical treatments aimed at improving overall skin appearance and health.

Summary: As a hallmark of aging, cellular senescence, an essentially irreversible cell cycle arrest with apoptosis resistance and a secretory phenotype, manifests across skin layers by affecting epidermal and dermal cells. Knowledge of skin-specific senescent cells, such as melanocytes (epidermal aging) and fibroblasts (dermal aging), will promote our understanding of age-related skin changes and how to optimize patient outcomes in esthetic procedures.

Key messages: This review provides an overview of skin aging in the context of cellular senescence and discusses senolytic intervention strategies to selectively target skin senescent cells that contribute to premature skin aging.

Introduction: Recent research on the gut deepens people's understanding of the role of gut microbe-metabolites in longevity. However, most of the longevity population is female, and the gut microbe-metabolites associated with longevity in women remain unknown. Here, we hypothesize that the gut microbe-metabolite levels differed between the longevity women (LW, age ≥90) and the elderly women (EW, 60 < age <90).

Methods: We performed a cross-sectional study of 22 women in Guangxi longevity areas. 16S rRNA full-length sequencing, bioinformatic analysis, and nuclear magnetic resonance hydrogen spectra were determined to analyze the gut microbiota, microbial pathways, and fecal metabolites. We evaluated significant differences and relationships in gut microbe-metabolites and microbial pathways using the Mann-Whitney test and Spearman correlation, respectively.

Results: The EW experienced gut dysbiosis characterized by a higher Firmicutes/Bacteroidetes (F/B) value. The LW showed a higher abundance of Bacteroides and Alistipes, which might support health maintenance. Moreover, LW enriched alanine, aspartate, and glutamate metabolism, histidine metabolism, and pyruvate metabolism, leading to major changes in histidine, fumaric acid, acetate, valine, and aspartate. Interestingly, the most valuable metabolic pathway based on differential fecal metabolites confirmed the KEGG microbial pathway "alanine, aspartate, and glutamate metabolism" enriched in LW. Impressively, Bacteroides and Alistipes were positively correlated with alanine, aspartate, and glutamate metabolism, thus improving the level of aspartate, which could be a particular pathway related to longevity.

Conclusion: The enriched gut genus and microbial pathways in LW showed a significant correlation, which might mediate the production of metabolites related to longevity.