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

There is growing interest in whether adult vaccines such as shingles vaccine may slow biological aging beyond preventing acute infections. Using data from the nationally representative U.S. Health and Retirement Study, we examined whether shingles vaccination is associated with more favorable profiles across seven biological aging domains: inflammation, innate and adaptive immunity, cardiovascular hemodynamics, neurodegeneration, and epigenetic and transcriptomic aging, as well as a composite biological aging score. Analyses included adults aged 70+ in 2016 (n = 3,884), with biological measures drawn from venous blood, flow cytometry, and physical assessments. Weighted linear regressions adjusted for sociodemographic, and health covariates. Shingles vaccination was significantly associated with lower inflammation scores (b=-0.14, p = 0.0027), slower epigenetic (b=-0.17, p = 0.0001) and transcriptomic aging (b=-0.19, p < .0001), and a lower composite biological aging score (b=-0.18, p = 0.0002), suggesting potential benefits for systemic inflammation, molecular and overall biological aging. In contrast, vaccination was linked to higher adaptive immunity scores (b = 0.09, p = 0.0133), an unexpected finding warranting further investigation. Timing analyses indicated that epigenetic, transcriptomic and overall composite biological aging improvements were most pronounced within three years post-vaccination, with slower aging persisting beyond this window. The results support the hypothesis that shingles vaccination may influence key biological systems relevant to aging, though effects appear domain-specific and vary over time. Longitudinal studies are needed to confirm these patterns and explore implications for long-term health. This study adds to emerging evidence that vaccines could play a role in strategies to promote healthy aging by modulating biological systems beyond infection prevention.

Vascular dementia (VaD) is a leading cause of cognitive decline, yet its underlying molecular mechanisms remain incompletely understood. This study aims to investigate the alterations associated with VaD in neuronal and endothelial cells by integrating single-nucleus RNA sequencing (snRNA-seq) with microarray data from postmortem VaD brain tissues. Using high-dimensional weighted gene co-expression network analysis (hdWGCNA) and machine learning approaches, we identified SOX6 in neurons and LDLRAD3 in endothelial cells as key factors associated with VaD pathology. Functional enrichment analyses revealed that glutamatergic synapses and MAPK signaling are critical pathways in neurons, while the MAPK signaling pathway, lipid metabolism, and atherosclerosis in endothelial cells contribute to VaD progression. In a mouse model of post-stroke cognitive impairment induced by transient middle cerebral artery occlusion, SOX6 and LDLRAD3 were significantly upregulated at both the mRNA and protein levels, supporting their roles in VaD. These findings provide novel insights into potential therapeutic targets for VaD and highlight the importance of endothelial and neuronal interactions in disease progression.

Background: Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive memory decline. The increasing prevalence of AD has attracted considerable attention globally. The glucagon-like peptide-1 analog, liraglutide, a drug widely used in the treatment of type 2 diabetes, has shown promising neuroprotective effects in AD, including enhancing neuronal survival, reducing amyloid beta protein accumulation, improving synaptic plasticity, and reducing tau protein hyperphosphorylation. However, its potential impact on cognitive function remains unclear.

Methods: We evaluated the effects of liraglutide (25 nmol/day for 8 weeks) on the cognitive ability of 12-month-old 5 × familial AD (FAD) mice. The Morris water maze test was used to evaluate the spatial learning ability of mice. Histological evaluations were performed by Nissl staining and transmission electron microscopy. Neuroinflammation was detected by double immunofluorescence staining and enzyme-linked immunosorbent assay. Protein expression in the cortex and hippocampus was detected by immunohistochemistry and Western blotting.

Results: The spatial cognitive ability improved in 5 × FAD mice after liraglutide administration and was associated with an increased number of pyramidal cells in the cortex and hippocampus. Liraglutide also alleviated ultrastructural changes in the chemical synapses and reduced both local and systemic inflammation in AD mice. Furthermore, liraglutide reduced amyloid β protein expression, which may be associated with the regulation of nuclear factor kappa B/beta-secretase 1 pathways in AD mice.

Conclusions: The potential of liraglutide to improve cognitive function in AD mice offers an effective pharmacological approach for treating neurodegenerative diseases.

Background: The relationship between pain characteristics and chronic disease development in aging populations remains poorly understood. This study explored associations between early pain exposure and incident chronic diseases in older adults through epidemiological and genetic analyses.

Methods: Using data from China Health and Retirement Longitudinal Study (CHARLS) and English Longitudinal Study of Ageing (ELSA), participants were classified by pain trajectories across consecutive surveys: "now stronger/more sites/more frequent, previously stronger/more sites/more frequent, persistently pain-free, persistently strong/multiple/frequent." Cohorts were followed for incident chronic conditions through 2018 (CHARLS) and 2015 (ELSA). Mendelian randomization (MR) examined causal relationships between multisite chronic pain and disease outcomes.

Results: Early pain trajectory changes were significantly associated with increased incidence of multiple chronic diseases. Participants with "persistently strong pain" or "now stronger pain" demonstrated 37%-267% increased disease risks, particularly for chronic lung disease (HR 2.11, 95% CI: 1.52-2.94) and memory-related diseases (HR 3.67, 95% CI: 1.15-11.71); those with "previously stronger pain" remained associated with 24%-124% elevated risks, especially for liver disease (HR 2.24, 95% CI: 1.56-3.22). "Persistently multiple sites" or "now more sites" trajectories were associated with 58%-275% higher risks; "previously more sites" was associated with 39%-203% elevated risks. "Persistently frequent" pain was associated with 62%-131% increased risks. MR confirmed genetic associations between multisite chronic pain and 30 chronic diseases.

Conclusions: The burden of chronic pain in older adults has been underestimated by overlooking its potential association with elevated risks across multiple chronic diseases. Monitoring pain intensity, sites, and frequency should be integrated into geriatric evaluation to promote healthy aging.

Compounds promoting anabolic effects on muscle and bone may offer an ideal treatment for osteosarcopenia while potentially impacting healthspan and lifespan. We previously demonstrated the anabolic effects of picolinic acid (PIC), a tryptophan metabolite, on bone both in vitro and in vivo. However, its effects on muscle and potential additional effects on lifespan and healthspan are not yet fully understood. This study aimed to investigate PIC's effects on muscle cells in vitro and its impact on mobility and lifespan in an animal model. Murine C2C12 and human myoblasts were treated with PIC (1, 50, and 100 µM) or vehicle for 5 days. Myogenic regulatory factors (MRFs) were evaluated, and the fusion index and myotubules' length were calculated at timed intervals (day 1, 3, and 5). In vivo, Caenorhabditis elegans were treated with increasing doses of PIC, and their lifespan and rate of movement (thrashing) were evaluated at timed intervals. PIC-treated myoblasts showed a higher and earlier expression of MRFs. On day 3, PIC-treated myotubes were significantly more fused and longer when treated with PIC than vehicle-treated controls. C. elegans treated with 1 mM of PIC showed a significantly longer lifespan. In addition, the mobility of PIC-treated C. elegans was significantly increased at all timed points. In conclusion, this study demonstrates that, besides its anabolic effect on bone, PIC has an anabolic effect on muscle, which is also associated with a longer lifespan in PIC-treated C. elegans. This evidence opens up promising avenues for further exploration of PIC as a novel therapy for osteosarcopenia with additional effects on healthspan and lifespan.

Background: Sleep disturbances and cardiovascular disease are common and often co-occur in middle-aged and older adults, but less is known about associations of sleep with cardiorespiratory fitness (CRF) and energy efficiency in these populations. We examined cross-sectional associations of accelerometer-derived sleep metrics with CRF, walking energetics, and resting metabolic rate (RMR), and explored whether associations were moderated by age, sex, and race.

Methods: We studied 263 participants from the Baltimore Longitudinal Study of Aging (mean age 72.7 ± 10.1 years, 53.6% women). Predictors included total sleep time (TST), sleep efficiency (SE), sleep onset latency, wake after sleep onset, and average wake bout length (WBL). Outcomes included measures of CRF (ie, maximal oxygen consumption [VO2peak]) and energetic efficiency (ie, energetic cost of walking and RMR).

Results: After adjusting for demographics, comorbidities, and self-reported physical activity, longer WBL was associated with lower VO2peak (B= -1.01 ml/kg/min, P < .01) and higher RMR (B = 43.25 kcal, P < .05), lower SE was associated with lower VO2peak (B = 1.07 ml/kg/min, P < .01), and shorter TST was associated with lower VO2peak (B = 0.33 ml/kg/min, P < .05). Higher SE was associated with lower RMR among middle-aged adults but not older adults (interaction P-value < 0.05).

Conclusion: Shorter TST, longer WBL, and lower SE are associated with poorer CRF and energetic efficiency among middle-aged and older adults. Longitudinal studies are needed to understand the temporality of these associations and potential targets for interventions in these populations.

Background: Ageing is a complex process, starting early in life, manifesting across a hierarchy of biological bodily domains with heterogeneity by sex and increasing age. Several molecular and organ-level biological ageing measurements have been developed. Reported associations of these measurements with ageing-related functional health status are typically limited to cross-sectional research and studies in old people only.

Methods: Using data from UK Household Longitudinal Study, we examined associations between composite biological ageing measures (Biological Health Score and DNA methylation algorithms) and grip strength, cognitive function, Short Form 12-item Survey scores, self-rated health cross-sectionally (up to 13,231 participants), as well as subsequent 12-year trajectories of Short Form 12-item Survey scores and self-rated health (up to 112,915 observations).

Results: Accelerated biological ageing was found to be associated with worse functioning both cross-sectionally and longitudinally. However, associations can be moderated by sex and age group. For example, longitudinally, Biological Health Score was negatively associated with self-rated health (coefficient = -0.06) with a moderating effect of sex (coefficient = -0.02, p < 0.05; male = reference) and some age groups (40-52 years: coefficient = -0.04, p < 0.001; 53-65 years: coefficient = -0.03, p < 0.01; reference = 16-39 years), but not for the oldest group (66+ years: coefficient = -0.01, p = 0.34).

Conclusion: We conclude that measures of biological age are associated with individual functioning trajectories across the entire adult age span, and studies should consider sex differences and examine the entire age range to fully capture distinct facets of ageing complexity.