Experimental gerontology最新文献

Background: In light of growing evidence highlighting interactions between cardiac and brain health, we investigated associations of biomarkers of neurodegenerative diseases with adverse outcomes (all-cause and cardiovascular mortality, major cardiovascular events, and stroke) in persons with chronic coronary syndrome (CCS).

Methods: We used data from a cohort of persons with CCS for whom major adverse events were recorded over a follow-up of 20 years. We measured biomarkers of neurodegenerative diseases in baseline blood samples, using the Single-Molecule Array Technology on a HD-1 Analyzer. These include biomarkers of neuronal (neurofilament light chain (NfL) (n = 379)) and glial neurodegeneration (glial fibrillary acidic protein (GFAP) (n = 379)), and Alzheimer's disease pathology (phosphorylated tau181 (n = 379), total tau (n = 377), and amyloid β (Aβ₄₀, Aβ₄₂, Aβ₄₂/Aβ₄₀) (n = 377)). We applied Cox-proportional hazards models to evaluate associations of these biomarkers with adverse outcomes, adjusting for covariates and exploring interactions with apolipoprotein E (ApoE) ε4 genotype.

Results: Participants with higher NfL levels had increased rates of all-cause and cardiovascular mortality (Hazard ratio per increase by one standard deviation (95 % confidence interval): all-cause mortality: 1.36 (1.10-1.68); cardiovascular mortality: 1.42 (1.05-1.93)). The Aβ₄₀/Aβ₄₂-ratio was linked to incident stroke (0.72 (0.52-1.00)). Associations of GFAP with all-cause mortality and incident stroke were depending on ApoE ε4 genotype. The other biomarkers were not significantly associated with the studied outcomes.

Conclusions: In persons with CSS, NfL and the Aβ₄₀/Aβ₄₂-ratio were related to mortality and incident stroke, respectively, whereas associations of GFAP with adverse outcomes varied by ApoE genotype. These biomarkers might play a role in linking aging, cardiovascular and neurodegenerative diseases.

Background: Aging is a complex biological process that disrupts tissue structure and impairs physiological function, which contributes to the development of age-related diseases such as cardiovascular disorders. However, effective treatment strategies are lacking.

Objective: To investigate the geroprotective effects of Lycium barbarum glycopeptide (LbGp) and its potential mechanisms in a D-galactose-induced accelerated aging mouse model.

Methods: Mice were subcutaneously injected with D-galactose (500 mg/kg/day) for 12 weeks to induce aging, while LbGp was orally administered (100 mg/kg/day) throughout the study. The geroprotective effects of LbGp were assessed by behavioral tests, cardiac echocardiography, pathohistological and transcriptomic analyses. Transmission electron microscopy was used to observe the ultrastructure of mitochondria. Mitochondrial stress assays and JC-1 fluorescent probe were conducted to evaluate mitochondrial function. Flow cytometer and western blot were performed to assess mitophagy flux.

Results: LbGp treatment improved the aging phenotypes of D-galactose-induced mice, with a pronounced enhancement in cardiac function compared to neurocognitive and skeletal muscle functions. Transcriptome analysis indicated that LbGp ameliorated energy metabolism in the heart. Mitochondrial assays revealed LbGp improved mitochondrial function and preserved structural integrity of the mitochondrial inner membrane. LbGp attenuated mitochondrial fission and restored impaired PINK1/Parkin-mediated mitophagy pathway caused by D-galactose in cardiomyocytes.

Conclusion: LbGp can ameliorate aging phenotypes and enhance cardiac metabolism by activating the PINK1/Parkin-mediated mitophagy pathway in D-galactose-induced mice. These findings underscore its potential as a therapeutic agent for aging and aging-related cardiovascular diseases.

Aging is a complex biological process characterized by increased inflammation and susceptibility to various age-related diseases, including cognitive decline, osteoporosis, and type 2 diabetes. Exercise has been shown to modulate mitochondrial function, immune responses, and inflammatory pathways, thereby attenuating aging through the regulation of exerkines secreted by diverse tissues and organs. These bioactive molecules, which include hepatokines, myokines, adipokines, osteokines, and neurokines, act both locally and systemically to exert protective effects against the detrimental aspects of aging. This review provides a comprehensive summary of different forms of exercise for older adults and the multifaceted role of exercise in anti-aging, focusing on the biological functions and sources of these exerkines. We further explore how exerkines combat aging-related diseases, such as type 2 diabetes and osteoporosis. By stimulating the secretion of these exerkines, exercise supports healthy longevity by promoting tissue homeostasis and metabolic balance. Additionally, the integration of exercise-induced exerkines into therapeutic strategies represents a promising approach to mitigating age-related pathologies at the molecular level. As our understanding deepens, it may pave the way for personalized interventions leveraging physical activity to enhance healthspan and improve quality of life.

Purpose: This study aimed to explore the association and prediction of hip abduction-adduction and knee flexion-extension isokinetic absolute and relative strength and power at 60°/s and 180°/s from functional tests performance (i.e., Up-and-Go Test [seconds], 30-Second Chair Stand Test [repetitions and relative and allometric power], 30-Second Arm Curl Test [repetitions], and 6-Minute Walk Test [meters]) in older adults.

Methods: Five hundred and fifty participants (404 women; age: 69.12 ± 5.29 years) enrolled in this cross-sectional study. Participants attended the laboratory once. Isokinetic concentric-concentric strength was assessed before physical fitness tests. Agility and dynamic tests were completed before strength and aerobic resistance tests within the physical fitness tests.

Results: Significant trivial-to-moderate correlations (positive and negative) were found between all the tests and the isokinetic strength and power of the knee and the hip. The performance in the UGT and 6MWT showed the best direct correlations with isokinetic strength and power (|r| = 0.09-0.48), and the 30CS and 30 AC showed inconsistent positive and negative correlations (r = -0.46-0.44). Significant regression equations including the functional tests, age, and sex were found, with higher values for knee isokinetic strength and power (R² = 0.19-0.44) compared to hip (R² = 0.09-0.35) and no clear pattern regarding better or worse predictability at higher angular velocities.

Conclusions: Isokinetic knee and hip strength and power are associated with functional fitness in older adults. The functional fitness tests, along with age and sex are predictive variables of older adults' lower-limb isokinetic strength, although explaining at most 44 % of the variance.

Objective: To investigate the genetic causality for the insomnia and common orthopedic diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoporosis (OP), and gout (GT).

Methods: The genome-wide association study (GWAS) summary data on insomnia were obtained from a published study, while the GWAS summary data on RA, AS, OP, and GT were sourced from the FinnGen consortium. We utilized the TwoSampleMR package of the R software (version 4.1.2) to conduct a two-sample Mendelian randomization (MR) analysis. Our primary method of analysis was the random-effects inverse variance weighted (IVW) approach. Subsequently, we conducted a series of sensitivity analyses for the MR analysis.

Results: The MR analysis revealed a positive genetic causal relationship between insomnia and RA (P = 0.016, odds ratio [OR] 95 % confidence interval [CI] = 1.112 [1.020-1.212]). However, no significant genetic causal relationship was observed between insomnia and AS (P = 0.194, OR 95 % CI = 1.121 [0.944-1.331]), OP (P = 0.788, OR 95 % CI = 1.016 [0.904-1.142]), and GT (P = 0.757, OR 95 % CI = 1.018 [0.912-1.136]). The MR analysis did not exhibit heterogeneity, horizontal pleiotropy, outlier effects, or dependence on a single SNP, and demonstrated normal distribution, which guaranteed the robustness of the results.

Conclusion: The results of this study suggest that insomnia may be a significant risk factor for RA, and controlling insomnia may represent a promising strategy for preventing RA. While insomnia was not observed to be associated with AS, OP, and GT at the genetic level, other levels of association cannot be excluded.

Background: Age-related hearing loss (ARHL) is a common sensory disorder with significant public health implications. However, few effective treatment options are available. Mendelian randomization (MR) has been used to repurpose existing drugs and identify new therapeutic targets. Therefore, we performed a systematic genome-wide MR of drug-eligible individuals to explore potential therapeutic targets for ARHL.

Methods: We obtained data on the expression quantitative trait locis (eQTLs) of druggable genes, which were then subjected to two-sample MR analyses and co-localisation analyses with data from the ARHL genome-wide association study to identify genes highly associated with ARHL. Additionally, we conducted phenome-wide research, enrichment analysis, protein network construction, drug prediction, and molecular docking to help develop more effective and targeted therapeutic treatments.

Results: Overall, the MR analysis of eQTL data showed that 14 drug targets were significantly associated with ARHL. GO analysis of 14 potential targets revealed their primary involvement in biological processes such as the endoplasmic reticulum unfolded protein response, ER-nucleus signaling pathway, and fibroblast apoptotic process. Additionally, important cellular components include the Bcl-2 family of proteins and the endoplasmic reticulum lumen. After filtering using methods such as phenome-wide research, enrichment analysis, protein network construction, drug prediction, and molecular docking, six potentially druggable genes (BAK1, AMFR, LAMP3, STK17B, ACP5, and CD9) and six drugs (beclomethasone, propyl pyrazole triol, momelotinib, monoisoamyl-2,3-dimercaptosuccinate, pterostilbene, and naftidrofuryl) that may affect ARHL outcomes were finally identified.

Conclusions: Our findings identified 14 potential drug targets for ARHL. These findings offer promising leads for more effective treatments for ARHL and help determine the priority of drug development, potentially reducing costs.

Background: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a newly developed lipid parameter that's used to evaluate cardiovascular disease risk. However, its association with sarcopenia risk has not been explored before.

Methods: Data on NHHR and sarcopenia were based on the secondary analysis of the years 2011-2018 of National Health and Nutrition Examination Survey (NHANES) dataset. NHHR was nature log-transformed (LnNHHR) to achieve a normal distribution. A multivariate logistic regression and a restricted cubic spline (RCS) model adjusted for associated factors were utilized to evaluate the correlation between NHHR and sarcopenia. Subgroup and sensitivity analyses were conducted to verify the robustness of the findings.

Results: The study cohort comprised 7069 participants, of whom 6497 (91.91 %) were sarcopenia-free, and 572 (8.09 %) exhibited sarcopenia. A significant increase in NHHR was observed in the sarcopenia group compared to the non-sarcopenic group (P < 0.001). Multivariate logistic regression analysis revealed that sarcopenia was independently linked to NHHR [odds ratio (OR): 1.394, P = 0.007]. A linear relationship was identified between NHHR and sarcopenia risk (P_non-linear = 0.108). Interaction analysis indicated that the relationship between NHHR and sarcopenia risk was not significantly modified by gender, sex, poverty income ratio, education, smoking status, or race.

Conclusion: NHHR was significantly associated with an elevated risk of sarcopenia among U.S. adults. Further research is warranted to elucidate the underlying physiological mechanisms through which NHHR influences sarcopenia development.

Non-pharmacologic interventions are effective for persons showing mild cognitive impairment (MCI) and Alzheimer's disease (AD). We used activation likelihood estimation (ALE) meta-analysis to systematically quantify the results of 19 neuroimaging studies in order to identify brain regions in which patients showed stable increases or decreases in activation after interventions. We also tested the moderating effects of disease stage (MCI vs. AD) and intervention modality (cognitive training vs. exercise intervention). The results showed increased activation in the cuneus, precuneus and medial frontal gyrus in the combined groups after treatment, whereas the anterior cingulate gyrus showed decreased activation. Secondly, in the MCI group there was increased activation in the precuneus and precentral gyrus after treatment, whereas there was decreased activation in the anterior cingulate gyrus; in the AD group there was only increased activation after treatment, including in the lingual gyrus and bilateral superior temporal gyrus. Finally, the bilateral cuneus and precentral gyrus showed increased activation after cognitive training, while bilateral insula, among others, showed decreased activation. This suggests that there are brain activation changes after non-pharmacological treatments for MCI and AD patients, but that the treatment mechanisms are moderated by stage and intervention modality. Future studies could continue to explore specific neural mechanisms involved in different intervention conditions for these patients.

The increasing prevalence of Alzheimer's disease (AD) calls for a comprehensive exploration of its complex etiology, with a focus on sex-specific vulnerability, particularly the heightened susceptibility observed in postmenopausal women. Neurometabolic alterations during the endocrine transition emerge as early indicators of AD pathology, including reduced glucose metabolism and increased amyloid-beta (Aβ) deposition. The fluctuating endocrine environment, marked by declining estradiol levels and reduced estrogen receptor beta (ERβ) activity, further exacerbates this process. In this context, here we explore the potential of forkhead box O3 (FOXO3) as a critical mediator linking metabolic disturbances to hormonal decline. We propose that FOXO3 plays a key role in the intersection of menopause and AD, given its dysregulation in both AD patients and postmenopausal women, modulating cellular metabolism through interactions with the AMPK/AKT/PI3K pathways. This relationship highlights the intersection between hormonal changes and increased AD susceptibility. This review aims to open a discussion on FOXO3's contribution to the metabolic dysregulation seen in menopause and its impact on the progression of AD. Understanding the functional role of FOXO3 in menopause-associated metabolic changes could lead to targeted therapeutic strategies, offering novel insights for managing for this condition.

Purpose: Recently, the World Health Organization has emphasized the importance of a healthy lifestyle in reducing severe illnesses and premature mortality. To evaluate this, the Healthy Lifestyle Score (HLS), which focuses on health protecting behaviors (e.g., smoking, alcohol consumption, physical activity, body mass index), is widely used. However, as HLS may fluctuate over time, there is increasing focus on monitoring HLS trends. Accordingly, this study aims to track HLS trajectories (HLST) and examine their association with mortality among middle-aged and older Koreans.

Methods: After excluding missing values, data from 6249 participants were analyzed using the group-based trajectory model (GBTM) to classify HLST, based on the first to fourth waves of the Korean Longitudinal Study of Aging (KLoSA). The chi-square test and Cox proportional hazards model were employed to examine the association between HLST and all-cause mortality over a 10-year follow-up period (December 31, 2012, to December 31, 2022; 3650 days).

Results: Three HLST groups were identified in the GBTM analysis. These were the Poor HLST (17.8 %), Average HLST (42.9 %), and Good HLST (39.4 %) groups. Compared to the good HLST, the poor HLST had higher mortality at 1 year (hazard ratio [HR]: 1.98, p: 0.029), 3 years (HR: 1.78, p: 0.001), 5 years (HR: 1.52, p: 0.002), 7 years (HR: 1.39, p: 0.002), and 10 years (HR: 1.40, p: 0.000). Furthermore, stratified analysis by sex, age, marital status and residential region showed that male, ≥65 years, single and urban area groups had a strong association between HLST and all-cause mortality.

Conclusion: The findings of this study underscore the necessity of policies and institutional measures grounded in community networks to mitigate the risk of all-cause mortality among vulnerable groups with persistently poor HLST.