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The association between doubly labeled water- and accelerometer-measured physical activity, brain volume, and cognitive function in older adults with cardiometabolic or functional risks
Regular physical activity is beneficial for brain health. However, no research has explored whether physical activity level (PAL) assessed by the doubly labeled water method (PAL-DLW) is associated with brain volume and cognitive function. We investigated whether PAL-DLW, accelerometer-assessed PAL (PAL-Acc), and components of physical activity are associated with brain volume and cognitive function in older adults. We analyzed data from 49 participants with cardiometabolic or functional risks...
Age-associated inflammation is accompanied by JAK1-STAT1 signaling activation, megakaryocyte apoptosis, and enhanced thrombopoiesis in naturally aged mice
CONCLUSION: Age-associated inflammation is accompanied by activation of the IL6ST/JAK1-STAT1 signaling pathway, increased megakaryocyte apoptosis, and enhanced thrombopoiesis in aged mice. These findings suggest that inflammation-driven megakaryocyte remodeling may represent a compensatory mechanism for sustaining platelet production during aging and may contribute to the heightened thrombotic risk observed in older individuals.
PRMT6 drives hearing loss by promoting asymmetric arginine dimethylation-mediated FOXG1 degradation and suppressing mitophagy
CONCLUSION: PRMT6 exacerbates D-gal-induced cochlear aging by promoting asymmetric arginine dimethylation of FOXG1, accelerating FOXG1 degradation, and inhibiting mitophagy. The PRMT6-FOXG1-mitophagy axis represents a potential therapeutic target for D-gal-induced cochlear aging.
Prediction of mild cognitive impairment progression using time-sensitive multimodal biomarkers
Alzheimer's disease (AD) develops silently for years before symptoms emerge, making early identification of at-risk individuals essential for prevention trials and early intervention. We tested whether combining neurophysiological, imaging, and blood biomarkers improves prediction of progression to mild cognitive impairment (MCI) in cognitively unimpaired older adults with a family history of AD (n = 102; 31 progressors; mean follow-up of 5.9 years). Magnetoencephalography, magnetic resonance...
MicroRNA-34a suppresses KLF2 to promote pathological angiogenesis through the CXCR4/CXCL12 pathway in age-related macular degeneration
Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute vision loss, but high treatment burden and loss of efficacy with chronic therapy highlight the need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as a key regulator in aging and age-related diseases, but its role in neovascular AMD is...
Aging-associated increase of GATA4 levels in articular cartilage is linked to impaired regenerative capacity of chondrocytes and osteoarthritis
Although the causal association between aging and osteoarthritis (OA) has been documented, our understanding of the underlying mechanism remains incomplete. To define the regulatory molecules governing chondrocyte aging, we performed transcriptomic analysis of young and old human chondrocytes from healthy donors. The data predicted that GATA-binding protein 4 (GATA4) may play a key role in mediating the difference between young and old chondrocytes. Results from immunostaining and western blot...
Fully dry-processed electrodes for highly reversible aqueous zinc powder-based batteries
Aqueous zinc-ion batteries have advanced rapidly, but practical deployment is limited by excessive negative-to-positive (N/P) ratios (>50), decreasing the energy density. Zinc powder anodes can lower N/P, yet their high specific surface area accelerates parasitic reactions and shortens lifespan. Here we report a high-loading and highly reversible dry-processed zinc powder anode with a non-electrochemically driven solid-electrolyte interphase (SEI). The dry process retains a homogeneous...
Mitochondrial stress activates ELT-2-dependent lysosomal proteostasis to extend lifespan in C. elegans
Mild mitochondrial stress could extend lifespan across species, yet the underlying mechanism remains unclear. Here, we show that inhibition of mitochondrial respiration induces a sustained transcriptional program that enhances lysosomal proteolysis during aging in Caenorhabditis elegans. Mechanistically, this response is primarily regulated by the intestinal GATA transcription factor ELT-2, which retains high expression and directly binds to GATA motifs in the promoters of lysosomal protease...
Normative age-related changes in resting-state EEG alpha power and theta/alpha ratio across eyes-open and eyes-closed conditions
Resting-state electroencephalography (EEG) provides a sensitive measure of large-scale neural dynamics and has been widely used to characterize age-related changes in brain function. However, many prior studies have relied on relatively small samples or single-condition recordings, limiting the generalizability of findings. In this study, we investigated normative age-related trajectories of EEG spectral features across eyes-closed (EC) and eyes-open (EO) conditions in a large cohort of healthy...
Latent profile analysis and analytical model construction based on heterogeneity of intrinsic capacity in Chinese older adults
CONCLUSION: This study delineates two IC profiles among Chinese older adults. The XGBoost-based model was explored for rapid IC profile classification. These findings highlight heterogeneity in IC and support the feasibility of a simplified digital approach, with external validation warranted.
Metabolic Dysfunction-Associated Steatotic Liver Disease and Risk of Depressive Symptoms in Older Adults
CONCLUSION: This study shows that the presence of MASLD is significantly associated with an increased risk of a worse depression trajectory. In subgroup analysis, this relationship was particularly pronounced amongst females and among individuals with key cardiometabolic morbidities such as dyslipidaemia.
Circular RNAs outperform established Alzheimer disease biomarkers
No abstract
Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer's disease
Myeloid cells, including microglia and perivascular macrophages, are central to Alzheimer's disease (AD) neurobiology, yet their role remains incompletely understood. We profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 donors spanning the lifespan and showing varying degrees of AD neuropathology. We delineated six subclasses comprising 13 transcriptionally distinct subtypes and identified adaptive changes associated with aging and AD progression. Here we show that a...
Exploring the link between body physiology and cognition: the role of the brain and aging
Epidemiological links between cognition and body physiology in aging are well established, but their strength and drivers remain unclear. Which physiological systems - from body composition to cardiovascular, pulmonary, renal, hepatic, immune, metabolic, and musculoskeletal - best predict cognition, and to what extent are cognition-body associations linked to brain variation across aging? We examined 19 physiological phenotypes alongside three neuroimaging modalities in over 30,000 UK Biobank...
Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer's disease
Myeloid cells, including microglia and perivascular macrophages, are central to Alzheimer's disease (AD) neurobiology, yet their role remains incompletely understood. We profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 donors spanning the lifespan and showing varying degrees of AD neuropathology. We delineated six subclasses comprising 13 transcriptionally distinct subtypes and identified adaptive changes associated with aging and AD progression. Here we show that a...