Aggregator

Atherosclerosis, a key pathological basis of cardio-cerebrovascular diseases, is closely associated with aging and endothelial cell senescence. The role of microRNAs (miRNAs) in regulating endothelial cell senescence and atherosclerosis remains incompletely understood. In this study, we discovered that miR-375-3p expression was significantly elevated in the serum of both aged and atherosclerotic mice. Overexpression of miR-375-3p induced endothelial cell senescence, evidenced by increased...

INTRODUCTION: The aging global population underscores the need to understand brain aging and its links to neurodegenerative diseases. While most brain aging studies use cognitive impairment as exclusion criteria, preclinical biomarkers may influence results, potentially masking early pathological effects. This study evaluates how preclinical AD and vascular biomarkers impact brain aging models in cognitively normal subjects.

Phil Krause applauds call by top agency official Vinay Prasad for better data, but says his approach is “destructive”

The progressive accumulation of amyloid beta (Aβ) plaques is a hallmark of Alzheimer's disease (AD). However, the biochemical mechanisms of their formation and the consequences associated with plaque formation remain elusive. In female 5xFAD and APP^(NL-G-F) mice, we map region-specific, plaque-associated lipids with large molecular coverage including isomers. We describe a multimodal framework that integrates matrix assisted laser desorption/ionization with laser-induced postionization...

Prime editing offers versatile genome modifications with therapeutic potential; yet its use to modulate neural circuitry remains underexplored. Here, we used adeno-associated viral vectors to deliver prime editors into the mouse brain and introduced the naturally occurring Adrb1^(A187V) variant of the β1-adrenergic receptor, linked to short sleep in humans and mice. Editing reached up to 28.1% in the cortex six months after intracerebroventricular injection and increased excitability of...

White matter hyperintensities (WMH) are an MRI-based biomarker associated with aging, Alzheimer's disease, and vascular dementia. Although the volume of WMH typically increases over time (growth) for individuals, WMH volume in some cases can also decrease (regress). This suggests the presence of active brain injury recovery mechanisms. Whether WMH regression reflects a true biological phenomenon or results from imaging artifacts or measurement errors, however, remains controversial. Here, we...

Sinus node dysfunction, a prevalent arrhythmia in aging populations, is characterized by fibrosis and loss of pacemaker activity, necessitating pacemaker implantation. Current therapies fail to reverse the underlying pathology. Small extracellular vesicles derived from human induced pluripotent stem cells possess regenerative potential but lack targeted delivery. Here, we engineer platelet membrane-fused vesicles that synergistically combine collagen targeting for ischemic injury homing with...

Glioblastoma (GBM) is a highly malignant tumor with a high postoperative recurrence rate. It is crucial to develop innovative and effective approaches to prevent its recurrence. Herein, we focus on the important roles of neutrophil extracellular traps (NETs) in the progression of GBM in mice and patients. Neutrophils accumulate around the surgical cavity and release NETs to promote the proliferation and migration of postoperative residual GBM cells. Injection of a hydrogel loaded with copper...

CONCLUSIONS: The RGGM model introduces a memory factor into its objective function, which assigns a greater weight to newer observations. This mechanism ensures the priority of new information during the modeling process, enhancing the model's adaptability. Furthermore, the model's structural parameters are solved recursively with each new observation, allowing the parameters to inherit information from previous data points. This recursive approach effectively improves prediction accuracy....

CONCLUSION: Affected by a variety of factors, the older person's low acceptance of institutional care remains consistent even when future disability is considered. This situation provides the background and ideas for China's current research on promoting social care services. For example, the nursing institutions should consider factors such as the age, education leveland income of the older person when designing elderly care services. The government can lower the threshold for the older person...

CONCLUSIONS: Hospitalizations for CVEs in elderly AF/AFL OAC treated patients increased the risk for all cause and CV mortality within 12 months from admission for AF/AFL. Hospitalization for HF bared the highest risk, but the residual stroke/TIA/SE risk was noteworthy.

UBB^(+1), a ubiquitin variant protein resulting from a frameshift in the ubiquitin-B gene, is a pathological hallmark of Alzheimer disease (AD). At the cellular level, UBB^(+1) disrupts the ubiquitin-proteasome system while inducing autophagy. Notably, UBB^(+1) itself is secreted via autophagosome-like vesicles. Here, we demonstrate that UBB^(+1) can be removed from the cell by degradative and secretory autophagy. Sequestosome 1 (SQSTM1)/p62 functions as a pivotal ubiquitin receptor for...

Regulatory T (Treg) cells express high levels of the IL-27R, and in the setting of infection and autoimmunity, the cytokine IL-27 promotes Treg cell activities that mitigate tissue pathology. However, IL-27 appears dispensable for Treg cell development and maintenance as lineage-specific depletion of the IL-27R on Treg cells does not impact these populations at steady state. In contrast, when mice were generated in which the Treg compartment comprised a mix of IL-27R-sufficient and -deficient...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuronal cell death, brain atrophy, and cognitive decline. Aggregation of Tau protein in neurons is a critical factor in the pathogenesis of AD. Tau aggregates increase as the disease progresses and contribute to neuronal cell death. This study investigated the role of ubiquitin-specific protease 10 (USP10) in Tau pathology and neuronal viability in AD. We found that the expression of USP10 was reduced in the...

The hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, synchronizing peripheral clocks through oscillations in core clock genes and proteins. Circadian disruption contributes to immunosenescence, aging, and neurodegenerative disorders such as Parkinson's disease (PD). Previous work from our group demonstrated age-related changes in circadian rhythms of clock genes, protein levels, and serotonin metabolism in the SCN and substantia nigra (SN) of male Wistar...

Aging is commonly attributed to accumulated damage, or evolved antagonistic genetic trade-offs, which lead to an accumulation of damage causing misexpression of genes necessary for longevity. We propose an atavistic dysregulation of gene expression at cellular and tissue levels during aging, framing aging as a gradual regression toward ancestral cellular states. Similarly to the atavistic model of cancer, in which cells revert to unicellular-like behavior, aging may result from the breakdown of...

CONCLUSION: ML algorithms can effectively predict the occurrence of frailty in Chinese elderly and identify significant factors associated with frailty. For datasets with complex feature interactions, LightGBM is preferable, while Random Forest offers improved stability and variance control. These findings support ML-based frailty screening and intervention strategies for aging populations.

Liver aging is characterized by pathological features including lipid deposition, exacerbated chronic inflammation, and increased cell death. Although exercise intervention has been proven effective in delaying liver aging, its fundamental biochemical mechanism remains unclear. This study utilized a naturally aged mouse model and an in vitro cellular senescence system to reveal, for the first time, the cascade mechanism by which β-hydroxybutyrate (β-HB), a core protective mediator induced by...