Gerontology最新文献

Introduction: Osteoarthritis (OA) is the most prevalent and debilitating joint disease without an effective therapeutic option. Multiple risk factors for OA have been identified, including abnormal chondrocyte miRNA secretion and circadian rhythms disruption, both of which have been found to cause progressive damage and loss of articular cartilage. Environmental disruption of circadian rhythms in mice predisposes animals to cartilage injury and OA.

Methods: The role of miR-195/497 cluster during OA progression was verified by mouse OA model with intra-articular injection of Agomir and Antagomir. We performed micro-CT analysis, Osteoarthritis Research Society International scores, and histological analysis in mouse knee joints. RNA sequencing was performed on the mouse cartilage cell line to explore the molecular mechanism of the miR-195/497 cluster and proteins in signaling pathway were evaluated using Western blot. Senescence-associated phenotypes were detected by Western blot, senescence β-galactosidase staining, and immunofluorescence.

Results: This study demonstrated that miR-195/497-5p expression is disrupted in OA with senescent chondrocytes. In addition, miR-195/497-5p influenced the circadian rhythm of mice chondrocytes by modulating the expression of the Per2 protein, resulting in the gradual degradation of articular cartilage. We found that the miR-195/497 cluster targets DUSP3 expression. The deletion of the miR-195/497 cluster increased the level of DUSP3 expression and decreased the levels of phosphorylated ERK 1/2 and CREB. Per2 transcription is upregulated by stimulating CREB and ERK 1/2 phosphorylation.

Conclusion: Our findings identify a regulatory mechanism connecting chondrocyte miR-195/497-5p to cartilage maintenance and repair and imply that circadian rhythm disturbances affected by miR-195/497-5p are risk factors for age-related joint diseases such as OA.

Introduction: The discovery of longevity molecules that delay aging and prolong lifespan has always been a dream of humanity. Sitagliptin phosphate (SIT), an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, is an oral drug commonly used in the treatment of type 2 diabetes (T2D). In addition to being antidiabetic, previous studies have reported that SIT has shown potential to improve health. However, whether SIT plays a role in the amelioration of aging and the underlying molecular mechanism remain undetermined.

Methods: Caenorhabditis elegans (C. elegans) was used as a model of aging. Lifespan assays were performed with adult-stage worms on nematode growth medium plates containing FUdR with or without the specific concentration of SIT. The period of fast body movement, body bending rates, and pharyngeal pumping rates were recorded to assess the healthspan of C. elegans. Gene expression was confirmed by GFP fluorescence signal of transgenic worms and qPCR. In addition, the intracellular reactive oxygen species levels were measured using a free radical sensor H2DCF-DA.

Results: We found that SIT significantly extended lifespan and healthspan of C. elegans. Mechanistically, we found that several age-related pathways and genes were involved in SIT-induced lifespan extension. The transcription factors DAF-16/FOXO, SKN-1/NRF2, and HSF-1 played important roles in SIT-induced longevity. Moreover, our findings illustrated that SIT-induced survival benefits by inhibiting the insulin/insulin-like signaling pathway and activating the dietary restriction-related and mitochondrial function-related signaling pathways.

Conclusion: Our work may provide a theoretical basis for the development of anti-T2D drugs as antiaging drugs, especially for the treatment of age-related disease in diabetic patients.

Introduction: The relationship among physiologic reserve, intrinsic capacity, and physical resilience has not been examined, and a conceptual model that includes these key determinants of healthy ageing is needed. This study aimed to test a conceptual model using real-world data to determine the relationships among physiologic reserve, intrinsic capacity, physical resilience, and clinical outcomes.

Methods: This longitudinal study was conducted at a 1,343-bed tertiary-care medical centre. Patients were eligible for inclusion if they were 65 years of age or older and able to communicate independently. Demographic factors, cumulative illness rating scale for geriatrics [CIRS-G] (assessing physiologic reserve), intrinsic capacity, physical resilience instrument for older adults [PRIFOR] (assessing physical resilience), and clinical frailty scale [CFS] were collected at admission. The CFS and EuroQoL 5-dimension 3-level questionnaire [EQ5D] were administered at discharge.

Results: The mean age of the 413 patients was 76.34 ± 6.72 (52.5% female). Two conceptual models were identified and supported. Specifically, the path coefficients in the two models showed that the CIRS-G had diverse associations with each intrinsic capacity domain, and that all intrinsic capacity domains (except vitality) were significantly associated with PRIFOR. Moreover, PRIFOR was significantly associated with follow-up CFS, baseline control, and EQ5D scores.

Conclusion: Physiologic reserve positively correlated with the cognitive and locomotive domains of intrinsic capacity. Moreover, older patients with better intrinsic capacity may have improved physical resilience, which may lead to better clinical outcomes. Efforts to improve the intrinsic capacity and physical resilience of older patients are necessary to promote healthy ageing.

Introduction: The association between specific motor capacity variables obtained in a laboratory and parameters of daily-life mobility performance (MP) obtained via wearables is still unclear. The Timed Up-and-Go (TUG) test is a widely used motor capacity tests available either as traditional hand-stopped TUG or as instrumented TUG (iTUG), providing specific information about its subphases. This study aimed to: (1) estimate the association between the TUG and specific parameters reflecting average and maximum daily-life MP, (2) estimate the benefits of the iTUG in terms of explaining MP in daily life compared to the TUG.

Methods: The present study was a cross-sectional analysis using baseline data of 294 older persons (mean age: 76.7 ± 5.3 years). Univariate linear regression analysis was performed to delineate the coefficient of determination between TUG time and participants' MP. MP variables containing mean cadence (MCA) to represent average performance and the 95th percentile of mean cadence of walks with more than three steps (p95>3stepsMCA) to represent maximum performance. To determine whether the iTUG variables give more information about MP, a stepwise multivariate regression analysis between iTUG variables and the p95>3stepsMCA variable to represent maximum performance was conducted.

Results: The univariate regression models revealed associations of the TUG with MCA (adjusted R2 = 0.078, p < 0.001) and p95>3stepsMCA (adjusted R2 = 0.199, p < 0.001). The multivariate stepwise regression models revealed a total explanation of maximum daily-life MP (p95>3stepsMCA) of the TUG (adjusted R2 = 0.199, p < 0.001) versus iTUG (adjusted R2 = 0.278, p < 0.010).

Discussion/conclusion: This study shows that the TUG better reflects maximum daily-life MP than average daily-life MP. Moreover, we demonstrate the added value of the iTUG for a more accurate estimation of daily MP compared to the traditional TUG. The iTUG is recommended to estimate maximum daily-life MP in fall-prone older adults. The study is a step toward a specific assessment paradigm using capacity variables from the iTUG to estimate maximum daily-life MP.

Introduction: In aging populations, the coexistence of multiple health comorbidities represents a significant challenge for clinicians and researchers. Leveraging advances in omics techniques to characterize these health conditions may provide insight into disease pathogenesis as well as reveal biomarkers for monitoring, prognostication, and diagnosis. Researchers have previously established the utility of big data approaches with respect to comprehensive health outcome measurements in younger populations, identifying protein markers that may provide significant health information with a single blood sample.

Methods: Here, we employed a similar approach in two cohorts of older adults, the Baltimore Longitudinal Study of Aging (mean age = 76.12 years) and InCHIANTI Study (mean age = 66.05 years), examining the relationship between levels of serum proteins and 5 key health outcomes: kidney function, fasting glucose, physical activity, lean body mass, and percent body fat.

Results: Correlations between proteins and health outcomes were primarily shared across both older adult cohorts. We further identified that most proteins associated with health outcomes in the older adult cohorts were not associated with the same outcomes in a prior study of a younger population. A subset of proteins, adiponectin, MIC-1, and NCAM-120, were associated with at least three health outcomes in both older adult cohorts but not in the previously published younger cohort, suggesting that they may represent plausible markers of general health in older adult populations.

Conclusion: Taken together, these findings suggest that comprehensive protein health markers have utility in aging populations and are distinct from those identified in younger adults, indicating unique mechanisms of disease with aging.

Introduction: Studies of community-dwelling older adults find subjective age affects health and functional outcomes. This study explored whether younger subjective age serves as a protective factor against hospital-associated physical, cognitive, and emotional decline, well-known consequences of hospitalization among the elderly.

Methods: This study is a secondary data analysis of a subsample (N = 262; age: 77.5 ± 6.6 years) from the Hospitalization Process Effects on Mobility Outcomes and Recovery (HoPE-MOR) study. Psychological and physical subjective age, measured as participants' reports on the degree to which they felt older or younger than their chronological age, was assessed at the time of hospital admission. Independence in activities of daily living, life-space mobility, cognitive function, and depressive symptoms were assessed at hospital admission and 1 month post-discharge.

Results: The odds of decline in cognitive status, functional status, and community mobility and the exacerbation of depressive symptoms were significantly lower in those reporting younger vs. older psychological subjective age (odds ratio [OR] = 0.68, 95% CI = 0.46-0.98; OR = 0.59, 95% CI = 0.36-0.98; OR = 0.64, 95% CI = 0.44-0.93; OR = 0.64, 95% CI = 0.43-0.96, respectively). Findings were significant after controlling for demographic, functional, cognitive, emotional, chronic, and acute health predictors. Physical subjective age was not significantly related to post-hospitalization outcomes.

Conclusion: Psychological subjective age can identify older adults at risk for poor hospitalization outcomes and should be considered for preventive interventions.

Introduction: The objective of this study was to examine whether a healthy lifestyle composite score of social engagement, physical activity, and Mediterranean diet adherence moderates the association between psychological distress and global cognitive decline among cognitively healthy older adults (67+ years of age at baseline).

Methods: A total of 1,272 cognitively intact older adults (Mage = 74.1 ± 4.1 years, 51.9% female) in the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) completed a series of self-reported questionnaires to measure psychological distress and lifestyle behaviors, and the Modified Mini-Mental Examination (3MS) to assess cognitive performance at baseline and annually over 3 years.

Results: Controlling for sociodemographic and health-related characteristics, greater psychological distress was associated with steeper cognitive decline over time among males (B = -0.07, 95% CI: [-0.12, -0.02]), but not females (B = 0.008, 95% CI: [0.03, 0.04]). Although a healthy lifestyle composite score did not statistically significantly moderate the distress-cognition relationship (B = -0.005, 95% CI: [-0.02, 0.01]), there was an association between higher psychological distress and greater cognitive decline at low levels of social engagement (B = -0.05, 95% CI: [-0.09, -0.006]), but not at high levels of social engagement (B = 0.02, 95% CI: [-0.03, 0.07]).

Conclusion: This study suggests that the potentially harmful impact of stress on cognitive function may be malleable through specific healthy lifestyle behaviors and emphasizes the importance of taking a sex-based approach to cognitive aging research.

Introduction: The optimal choice of dialysis modality remains contentious in older adults threatened by advanced age and high risk of comorbidities.

Methods: We conducted a systematic review and meta-analysis of cohort and case-control studies to assess mortality risk between peritoneal dialysis (PD) and hemodialysis (HD) in older adults using PubMed, Embase, and the Cochrane Library database from inception to June 1, 2022. The outcome of interest is all-cause mortality.

Results: Thirty-one eligible studies with >774,000 older patients were included. Pooled analysis showed that PD had a higher mortality rate than HD in older dialysis population (HR 1.17, 95% CI: 1.10-1.25). When stratified by co-variables, our study showed an increased mortality risk of PD versus HD in older patients with diabetes mellitus or comorbidity who underwent longer dialysis duration (more than 3 years) or who started dialysis before 2010. However, definitive conclusions were constrained by significant heterogeneity.

Conclusion: From the survival point of view, caution is needed to employ PD for long-term use in older populations with diabetes mellitus or comorbid conditions. However, a tailored treatment choice needs to take account of what matters to older adults at an individual level, especially in the context of limited survival improvements and loss of quality of life. Further research is still awaited to conclude this topic.

Introduction: It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI).

Methods: This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA + DHA (FA 800 μg/d + DHA 800 mg/d), FA (800 μg/d), DHA (800 mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months.

Results: During the 12-month follow-up, scores of full intelligence quotient (βDHA: 1.302, 95% CI: 0.615, 1.990, p < 0.001; βFA: 1.992, 95% CI: 1.304, 2.679, p < 0.001; βFA+DHA: 2.777, 95% CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA + DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA, and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05).

Conclusions: Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone.