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Perineuronal nets: Role in normal brain physiology and aging, and pathology of various diseases

6 months 2 weeks ago
Perineuronal nets (PNNs) are a specialized extracellular matrix in the central nervous system. They are widely distributed in the brain, with distribution patterns varying by brain region. Their unique structure and composition allow them to play an important role in a range of physiological and pathological activities. In this article, we review the composition and structure of PNNs across different life stages, and provide a detailed analysis and comparison of the region-specific distribution...
Kaiqi Zhu

Targeting CD38 immunometabolic checkpoint improves metabolic fitness and cognition in a mouse model of Alzheimer's disease

6 months 2 weeks ago
Protective immunity, essential for brain maintenance and repair, may be compromised in Alzheimer's disease (AD). Here, using high-dimensional single-cell mass cytometry, we find a unique immunometabolic signature in circulating CD4^(+) T cells preceding symptom onset in individuals with familial AD, featured by the elevation of CD38 expression. Using female 5xFAD mice, a mouse model of AD, we show that treatment with an antibody directed to CD38 leads to restored metabolic fitness, improved...
Javier María Peralta Ramos

Perineuronal nets: Role in normal brain physiology and aging, and pathology of various diseases

6 months 2 weeks ago
Perineuronal nets (PNNs) are a specialized extracellular matrix in the central nervous system. They are widely distributed in the brain, with distribution patterns varying by brain region. Their unique structure and composition allow them to play an important role in a range of physiological and pathological activities. In this article, we review the composition and structure of PNNs across different life stages, and provide a detailed analysis and comparison of the region-specific distribution...
Kaiqi Zhu

Auto-sumoylation of the yeast Ubc9 E2 SUMO-conjugating enzyme extends cellular lifespan

6 months 2 weeks ago
Calorie restriction (CR) provides anti-aging benefits through diverse processes, such as reduced metabolism and growth and increased mitochondrial activity. Although controversy still exists regarding CR-mediated lifespan effects, many researchers are seeking interventions that mimic the effects of CR. Yeast has proven to be a useful model system for aging studies, including CR effects. We report here that yeast adapted through in vitro evolution to the severe cellular stress caused by loss of...
Dong-Won Jeong

CITK modulates BRCA1 recruitment at DNA double strand breaks sites through HDAC6

6 months 2 weeks ago
Citron Kinase (CITK) is a protein encoded by the CIT gene, whose pathogenic variants underlie microcephalic phenotypes that characterize MCPH17 syndrome. In neural progenitors, CITK loss leads to microtubule instability, resulting in mitotic spindle positioning defects, cytokinesis failure, and accumulation of DNA double strand breaks (DSBs), ultimately resulting in TP53-dependent senescence and apoptosis. Although DNA damage accumulation has been associated with impaired homologous...
Giorgia Iegiani

Telomere Length and Cognitive Function Among Middle-Aged and Older Participants From Communities Underrepresented in Aging Research: A Preliminary Study

6 months 2 weeks ago
ObjectiveAccelerated biological aging is a plausible and modifiable determinant of dementia burden facing minoritized communities but is not well-studied in these historically underrepresented populations. Our objective was to preliminarily characterize relationships between telomere length and cognitive health among American Indian/Alaska Native (AI/AN) and Black/African American (B/AA) middle-aged and older adults.MethodsThis study included data on telomere length and neuropsychological test...
Lauren W Y McLester-Davis

Deep brain stimulation alleviates Parkinsonian motor deficits through desynchronizing GABA release in mice

6 months 2 weeks ago
High-frequency deep brain stimulation (DBS) at subthalamic nucleus (STN) is an effective therapy for Parkinson's disease (PD), but the underlying mechanisms remain unclear. Here we find an important role of asynchronous release (AR) of GABA induced by high-frequency stimulation (HFS) in alleviating motor functions of dopamine-depleted male mice. Electrophysiological recordings reveal that 130-Hz HFS causes an initial inhibition followed by desynchronization of STN neurons, largely attributable...
Zongyi Xu

A societal cost-benefit analysis of falls prevention in community-dwelling older people in the Netherlands

6 months 2 weeks ago
CONCLUSION: Structural implementation of evidence-based falls prevention can provide significant health benefits and net cost savings, supporting its implementation at the societal level. The SCBA offers guidance to policymakers on the optimal falls prevention programs for older people, reducing the disease burden of falls in the Netherlands.
Martien J M Panneman

Temozolomide promotes glioblastoma stemness expression through senescence-associated reprogramming via HIF1alpha/HIF2alpha regulation

6 months 2 weeks ago
A critical challenge in glioblastoma multiforme (GBM) treatment is that tumors recurring after temozolomide (TMZ) therapy become more malignant, exhibiting increased invasiveness and stemness compared to the primary tumor. However, the underlying mechanisms remain unclear. While the majority of GBM cells are eradicated by TMZ, a subset enters cell cycle arrest, adopts a senescence-associated secretory phenotype (SASP), and activates senescence-related signaling pathways. These cells eventually...
Pan Wang

From geroscience to precision geromedicine: Understanding and managing aging

6 months 2 weeks ago
Major progress has been made in elucidating the molecular, cellular, and supracellular mechanisms underlying aging. This has spurred the birth of geroscience, which aims to identify actionable hallmarks of aging. Aging can be viewed as a process that is promoted by overactivation of gerogenes, i.e., genes and molecular pathways that favor biological aging, and alternatively slowed down by gerosuppressors, much as cancers are caused by the activation of oncogenes and prevented by tumor...
Guido Kroemer

The role of microRNAs in dexamethasone-induced skeletal muscle atrophy

6 months 2 weeks ago
Muscle atrophy is characterized by a decrease in muscle mass, strength, and activity. Recently, it was determined that microRNAs (miRNAs) can regulate muscle atrophy and that dexamethasone (Dex), an allergy and autoimmune disorder treatment that can induce muscle atrophy. Therefore, this study was designed to identify miRNAs expressed in Dex-induced muscle atrophy in mice using small RNA sequencing. A total of 820 miRNAs were identified, with 58 miRNAs expressed explicitly in atrophic muscles....
Subi Ren