Gerontology最新文献

Introduction: The objective of this study was to examine the potential induction of senescence in vascular endothelial cells (VECs) by chronic intermittent hypoxia (CIH), a defining characteristic of obstructive sleep apnea (OSA). This investigation seeks to elucidate the underlying mechanisms that contribute to the development of cardiovascular diseases in patients with OSA, with a particular focus on CIH-induced vascular aging.

Methods: The BioSpherix-OxyCycler system was used to establish models of CIH in both rats and human umbilical vein endothelial cells (HUVECs). To assess VECs' senescence, various methods were employed including EdU incorporation assay, cell cycle analysis, senescence-associated β-galactosidase (SA-β-gal) staining, and senescence protein testing. Vascular aging was evaluated through measurements of carotid-femoral pulse wave velocity, intima-media thickness, and Ki67 immunohistochemical staining. In order to identify the molecular mechanisms associated with CIH-induced senescence in VECs, a bioinformatics study was conducted utilizing the Gene Expression Omnibus database.

Results: Under conditions of CIH, HUVECs exhibited inhibited proliferation, arrested cell cycle, increased activity of SA-β-gal, and elevated expression levels of p53 and p21 compared to HUVECs under normoxic conditions. Similarly, rats exposed to CIH displayed increased carotid-femoral pulse wave velocity, intima-media thickness, vascular permeability, and SA-β-gal activity in VECs, along with decreased expression of arterial Ki67. BTG3-associated protein (BANP) was found to be highly expressed in CIH-induced VECs. Furthermore, the overexpression of BANP resulted in the senescence of VECs, along with elevated levels of p53 phosphorylation and nuclear localization.

Conclusions: These findings demonstrate that CIH can induce VECs senescence and contribute to vascular aging. Additionally, BANP can induce VECs senescence by promoting p53 phosphorylation and nuclear retention. These discoveries offer novel insights into the increased cardiovascular risk associated with OSA, thereby presenting new possibilities for therapeutic intervention.

Introduction: Frailty is a crucial health issue among older adults. Growth differentiation factor 15 (GDF15) is associated with inflammation, oxidative stress, insulin resistance, and mitochondrial dysfunction, which are possible pathogeneses of frailty. However, few longitudinal studies have investigated the association between GDF15 and the incidence of frailty. Therefore, we investigated whether high serum GDF15 levels are associated with the incidence of frailty.

Methods: A total of 175 older adults (mean age: 77 ± 6 years; 63% women) with cardiometabolic diseases and no frailty out of the two criteria at baseline participated. Individuals with severe renal impairment or severe cognitive impairment were excluded. Serum GDF15 levels were measured at baseline. Patients were asked to assess frailty status at baseline and annually during follow-up using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). We examined the association between GDF15 tertiles and each frailty measure during follow-up (median 38-39 months). In the multivariate Cox regression analysis, with the GDF15 tertile groups as the explanatory variables, hazard ratios (HRs) and 95% confidence intervals (CIs) for incident frailty were calculated after adjusting for covariates and using the lowest tertile group as the reference.

Results: During the follow-up period, 25.6% and 34.0% of patients developed frailty, as defined by the mCHS and KCL, respectively. The highest GDF15 tertile group had a significantly higher incidence of mCHS- or KCL-defined frailty than the lowest GDF15 tertile group. Multivariate Cox regression analysis revealed that the adjusted HRs for incident mCHS- and KCL-defined frailty in the highest GDF15 tertile group were 3.9 (95% CI: 1.3-12.0) and 2.7 (95% CI: 1.1-6.9), respectively.

Conclusion: High serum GDF15 levels predicted the incidence of frailty among older adults with cardiometabolic diseases and could be an effective marker of the risk for frailty in interventions aimed at preventing frailty, such as exercise and nutrition.

Introduction: Hip fracture in older adults results in significant mortality and is one of the costliest fall-related injuries. The Australian Commission for Quality and Safety in Health Care hip fracture clinical care standards consolidate the best available evidence for managing this patient group; however, uptake is variable. The aim of this study was to evaluate the implementation and effectiveness of a multidisciplinary early activation mechanism and bundle of care (eHIP) on patient and health service outcomes.

Methods: This controlled pre- and post-test study was conducted from June 2019-June 2021 at a large regional hospital in Australia. We hypothesised that eHIP would result in at least 50% of hip fracture patients receiving six or more components of the ACSQHC Hip Fracture Clinical Care Standard. Secondary outcomes include hospital-acquired complication rates and acute treatment costs.

Results: There were 565 cases included for analysis. After implementation of eHIP (the post-period), 88% of patients received a correct activation of the eHIP pathway, sustained over 12 months. The proportion of patients receiving the primary outcome of six or more components increased from 36% to 49%. Care at presentation (pain and cognitive assessment) increased by 23%, and unrestricted mobilisation within 24 h improved by 10%. Prescription of appropriate analgesia improved 10-fold (5.2-57%), and patients receiving the gold standard fascia iliaca block increased from 68% to 88%. Acute treatment costs did not significantly change.

Discussion/conclusion: eHIP, a hip fracture care program incorporating evidence-based behaviour change theory, resulted in sustained improvements to patient care as recommended by the ACSQHC Hip Fracture Clinical Care Standard.

Introduction: Pneumonia is a common and devastating complication following hip fracture surgery in older patients. Time to surgery is a potentially modifiable factor associated with improved prognosis, and we aim to quantify the time-effect relationship between time to surgery and in-hospital postoperative pneumonia (IHPOP) and identify the effect of delayed surgery on the risk of IHPOP.

Methods: We analyzed clinical data of older hip fracture patients (≥60 years) undergoing surgical treatments at a tertiary referral trauma center between 2015 and 2020. Restricted cubic spline (RCS) was used to fit the time-effect relationship between time to surgery and IHPOP. Based on the results of RCS, we divided patients into two groups of "early surgery" and "delayed surgery." A 1:1 propensity score matching (PSM) analysis and multivariate conditional logistic regression analysis were performed to minimize the selection bias and determine the association magnitude. Subgroup analysis was conducted to assess potential interaction effects between delayed surgery and common risk factors for IHPOP.

Results: 3,118 eligible patients were included. The RCS curve showed an inverse S-shape trend and the relative risk of IHPOP decreased in the range of days 2-3 and increased on day 1 and day 3 or more post-injury, with the lowest point on day 3. PSM yielded 1,870 matched patients and delayed surgery (>3 days) was identified to be independently associated with IHPOP (relative ratio, 1.66; 95% confidence interval, 1.12-2.46; p value, 0.011). We observed positive interaction effects between delayed surgery and age of 80 years or more, female gender, COPD, heart disease, ASA score ≥3, anemia, and hypoproteinemia.

Conclusion: The relative risk of IHPOP decreased in the range of 2-3 days and increased on day 1 and day 3 or more post-injury. Delayed surgery (>3 days) was identified to be independently associated with a 1.66-fold increased risk of IHPOP.

Introduction: Frailty is conventionally diagnosed using clinical tests and self-reported assessments. However, digital health technologies (DHTs), such as wearable accelerometers, can capture physical activity and gait during daily life, enabling more objective assessments. In this study, we assess the feasibility of deploying DHTs in community-dwelling older individuals, and investigate the relationship between digital measurements of physical activity and gait in naturalistic environments and participants' frailty status, as measured by conventional assessments.

Methods: Fried Frailty Score (FFS) was used to classify fifty healthy individuals as non-frail (FFS = 0, n/female = 21/11, mean ± SD age: 71.10 ± 3.59 years), pre-frail (FFS = 1-2, n/female = 23/9, age: 73.74 ± 5.52 years), or frail (FFS = 3+, n/female = 6/6, age: 70.70 ± 6.53 years). Participants wore wrist-worn and lumbar-worn GENEActiv accelerometers (Activinsights Ltd., Kimbolton, UK) during three in-laboratory visits, and at-home for 2 weeks, to measure physical activity and gait. After this period, they completed a comfort and usability questionnaire. Compliant days at-home were defined as follows: those with ≥18 h of wear time, for the wrist-worn accelerometer, and those with ≥1 detected walking bout, for the lumbar-worn accelerometer. For each at-home measurement, a group analysis was performed using a linear regression model followed by ANOVA, to investigate the effect of frailty on physical activity and gait. Correlation between at-home digital measurements and conventional in-laboratory assessments was also investigated.

Results: Participants were highly compliant in wearing the accelerometers, as 94% indicated willingness to wear the wrist device, and 66% the lumbar device, for at least 1 week. Time spent in sedentary activity and time spent in moderate activity as measured from the wrist device, as well as average gait speed and its 95th percentile from the lumbar device were significantly different between frailty groups. Moderate correlations between digital measurements and self-reported physical activity were found.

Conclusions: This work highlights the feasibility of deploying DHTs in studies involving older individuals. The potential of digital measurements in distinguishing frailty phenotypes, while unobtrusively collecting unbiased data, thus minimizing participants' travels to sites, will be further assessed in a follow-up study.

Introduction: Few studies have investigated the association between frailty and subsequent body composition.

Methods: We performed separate linear mixed model analyses to study the associations between changes in the participant frailty status assessed by a frailty index (FI) and subsequent body mass index (BMI), lean mass index (LMI), fat mass index (FMI), and FMI to LMI ratio values assessed on three occasions over 17 years. The analyses were carried out among 996 participants spanning from age 57 to 84 years.

Results: With advancing age, LMI and BMI decreased, whereas FMI and FMI to LMI ratio increased. Participants with "stable frailty," followed by those with "increasing frailty" experienced faster decreases in LMI and faster increases in FMI and FMI to LMI ratio values from midlife into old age relative to those in the group "stable not frail." Contrastingly, those in the highest third of absolute annual increase in FMI and FMI to LMI ratio became more frail faster from midlife into old age relative to those in the lowest third.

Conclusions: We found evidence of an adverse health outcome of frailty where lean indices declined faster and fat indices and fat-to-lean ratios increased faster from midlife into old age. The changes resembled those that occurred with aging, but at a faster pace. The relationship between body composition and frailty is likely bidirectional, where high or increasing levels of fat are associated with the risk of becoming more frail earlier, but where a longer duration of frailty may increase the risk of faster age-related changes to body composition.

Introduction: Nearly, a quarter of older adults suffer from frequent foot pain, impacting their quality of life. While proper footwear can alleviate this, design issues often hinder regular use. This study evaluated novel therapeutic footwear, designed for aesthetics and custom fit, to reduce foot pain. We hypothesized that older adults would experience less foot pain and favor the new footwear over their own.

Methods: This 12-week crossover randomized controlled trial evaluated the effectiveness of OrthoFeet therapeutic footwear on reducing foot pain in older adults (n = 50, age = 65 ± 5, 18% male) with moderate to severe pain. Participants were assigned to either the AB or BA sequence. In AB, they wore OrthoFeet shoes for 6 weeks and then their own shoes for another 6 weeks; BA followed the reverse order. Pain and function were measured using the Foot Function Index. Acceptability was assessed through a technology acceptance model (TAM) questionnaire. Data collected at baseline, six, and 12 weeks were analyzed using t tests, χ2 tests, and generalized linear model.

Results: Compared to participants' own shoes, OrthoFeet shoes significantly reduced foot pain and disability. Notable improvements were observed in "foot pain at its worst," "foot pain at the end of the day," "overall pain score," and "overall Foot Function Index score," all showing statistically significant reductions (p < 0.050). Participants reported high adherence to wearing the OrthoFeet shoes, averaging 8 h per day and 5.8 days per week. TAM scores favored OrthoFeet shoes over participants' own shoes in terms of ease of use, perceived benefit, and intention to recommend. Significant differences were noted in components representing perceived joint pain relief (p < 0.001, χ2 = 21.228) and the intention of use as determined by the likelihood of recommending the shoes to a friend with a similar condition (p < 0.001, χ2 = 29.465). Additionally, a majority of participants valued the appearance of the shoes, with 66% prioritizing shoe appearance and 96% finding the study shoes more stylish than their previous ones.

Conclusion: This study underscores the significance of design and custom fit in promoting continuous wear for effective foot pain reduction in older adults. More research is needed on the intervention's long-term impacts.

Background: The aging process is complex, comprising various contributing factors influencing late-life conditions and eventual occurrence of chronic diseases that generate high financial and human costs. These factors include genetic proneness, lifestyle conducted throughout life, environmental conditions, as well as dietary aspects, among others, all together modulating precise pathways linked to aging, making longevity a multidimensional event.

Summary: Compelling evidence support the concept that nutritional determinants have major impact on the risk of age-associated non-communicable diseases as well as mortality. Nutrition research has turned in recent years from considering isolated nutrients or foods to focusing on combinations of foods in dietary patterns in relation to their associations with health outcomes. This narrative review focuses attention on dietary patterns that may contribute to healthy or unhealthy aging and longevity with examples of traditional dietary patterns associated with healthy longevity and reviewing the association of healthy plant-based and unhealthy ultra-processed diets with frailty, a condition that may be considered a hallmark of unhealthy aging.

Key message: There is currently accumulated evidence confirming the key role that dietary patterns mainly of plant origin may exert in modifying the risk of age-associated chronic diseases and healthy longevity. These types of dietary models, unlike those in which the use of ultra-processed food is frequent, are associated with a reduced risk of frailty and, consequently, with healthy aging.

Introduction: Previous studies have suggested that the D-dimer to fibrinogen ratio (DD/Fg) could be a potential predictor for deep vein thrombosis, pulmonary embolism, and stroke severity. However, the association between plasma DD/Fg and functional outcome following acute ischemic stroke (AIS) has been unclear.

Methods: Our study followed the STROBE guideline and used a prospective cohort design to investigate this association. A total of 454 patients with AIS were enrolled consecutively in our study, and the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were assessed for stroke severity and functional outcome, respectively.

Results: We found a significant difference in DD/Fg values between the three groups based on NIHSS scores at admission. Specifically, the DD/Fg values were higher in the poor functional outcome group (mRS score of 2-6) compared to the favorable functional outcome group (mRS score of 0-1) at the 1-year follow-up (p < 0.001). Additionally, the DD/Fg values were independently associated with poor functional prognosis at 1 year following the onset of stroke, even after adjusting for potential confounders (OR 9.21, 95% CI, 3.68-23.02, p < 0.001).

Conclusions: Our findings suggest that DD/Fg values at admission may serve as risk predictors for poor functional outcomes in patients with AIS 1 year after the stroke.