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Deep funding cuts could deprive millions of treatment and cause more than 350,000 extra deaths per year, report predicts

Synaptic Rho guanosine triphosphatase (GTPase) guanine nucleotide exchange factors (RhoGEFs) play vital roles in regulating the activity-dependent neuronal plasticity that is critical for learning. Ephexin5, a RhoGEF implicated in the etiology of Alzheimer's disease and Angelman syndrome, was originally reported in neurons as a RhoA-specific GEF that negatively regulates spine synapse density. Here, we show that Ephexin5 activates both RhoA and Cdc42 in the brain. Furthermore, using live imaging...

CONCLUSION: The prevalence of VI is high older (> 55 years) adults in Cameroon, with clear differences between men and women. The oldest individuals, and women appear to be most vulnerable. The identification of at-risk groups/persons through this cross-sectional study should make it possible to adapt public health strategies to contribute to the WHO objective of healthy ageing.

Ankle proprioception and attentional resources are crucial for maintaining balance and safely driving. However, research exploring the age-related integrity of ankle proprioception has yielded conflicting results, while the attentional demand of proprioceptive processing in seniors remains underexplored. We investigated how aging affects the interaction between proprioception and attention in healthy sedentary adults using a novel dual-task paradigm. Sedentary old and young adults performed an...

N⁴-acetylcytidine (ac⁴C) is deposited on diverse RNAs by N-acetyltransferase 10 (NAT10), a protein with high biological relevance for aging and cancer. We performed a comprehensive survey of ac⁴C using metabolic labeling, sodium cyanoborohydride chemical treatment coupled to next-generation sequencing (NGS), and ac⁴C antibody-based cell and molecular biology techniques. Our analysis shows that NAT10-dependent ac⁴C-acetylation is robust in rRNA and specific tRNAs but low/spurious in mRNA. It also...

Osteoarthritis (OA) is a prevalent joint disease characterized by pain, disability, and loss of physical function, posing a challenge to public health. However, molecular mechanisms of OA pathogenesis have not been fully described. We report that tripartite motif containing 15 (TRIM15) is a regulator in chondrocyte senescence and OA. Our study revealed heightened expression of TRIM15 in chondrocytes of senescent cartilage from patients with OA and in aged wild-type mice. Using gain- and...

Despite remarkable progress in the biomarker field in recent years, local validation of plasma biomarkers of Alzheimer's disease (AD) and dementia is still lacking in Latin America. In this longitudinal cohort study of 145 elderly Brazilians, we assess the diagnostic performance of plasma biomarkers, based on clinical diagnosis and CSF biomarker positivity. Follow-up data of up to 4.7 years were used to determine performance in predicting diagnostic conversions. Participants were clinically...

The amyloid hypothesis has been a leading narrative concerning the pathophysiological foundation of Alzheimer's and Parkinson's disease. At the two ends of the hypothesis lie the functional protein monomers and the pathology-defining amyloid fibrils, while the early stages of protein aggregation are populated by polymorphic, transient and neurotoxic oligomers. As the structure and activity of oligomers are intertwined, here we show oligomers arising from liquid-liquid phase separation and...

Deep brain stimulation (DBS) is a neuroelectronic therapy for the treatment of a broad range of neurological disorders, including Parkinson's disease. Current DBS technologies face important limitations, such as large electrode size, invasiveness, and lack of adaptive therapy based on biomarker monitoring. In this study, we investigate the potential benefits of using nanoporous reduced graphene oxide (rGO) technology in DBS, by implanting a flexible high-density array of rGO microelectrodes (25...

Citalopram is effective in treating agitation in Alzheimer's dementia (AD), but it is associated with cognitive and cardiac risks, likely due to its R-enantiomer. Escitalopram, the S-enantiomer, may be an alternative. In this double-masked randomized (1:1) placebo-controlled trial, we assessed the efficacy and safety of escitalopram in treating agitation in AD after failure of a psychosocial intervention (PSI). Assessments occurred at enrollment, post-PSI (baseline) and at 3, 6, 9 and 12 weeks...

Senescence is a non-proliferative cellular state derived from aging or in response to exogenous insults, such as those that cause DNA damage. As a result of cancer treatments like cisplatin, certain tumor cells may undergo senescence. However, rather than being beneficial for patients, this is detrimental because these cells might proliferate again under specific conditions and, more importantly, because they synthesize and secrete molecules that promote the proliferation of nearby cells....

Aging is characterized by changes in gene expression, some of which can drive deleterious cellular phenotypes and senescence. The transcriptional activation of senescence genes has been mainly attributed to epigenetic shifts, but the changes in chromatin accessibility and its underlying mechanisms remain largely elusive in natural aging. Here, we profiled chromatin accessibility in human dermal fibroblasts (HDFs) from individuals with ages ranging from neonatal to octogenarian. We found that...

Maximizing metal-substrate interactions by self-reconstruction of coadjutant metastable phases can be a delicate strategy to obtain robust and efficient high-density single-atom catalysts. Here, we prepare high-density iridium atoms embedded ultrathin CoCeOOH nanosheets (CoCe-O-Ir(SA)) by the electrochemistry-initiated synchronous evolution between metastable iridium intermediates and symmetry-breaking CoCe(OH)(2) substrates. The CoCe-O-Ir(SA) delivers an overpotential of 187 mV at 100 mA...

Cycling positive electrode materials with high voltages and long lifetimes remains a challenge. On the one hand, operating electrodes at high voltages is usually accompanied by severe structural distortions and irreversible reactions. On the other hand, the significant volume variation upon Na^(+) insertion/extraction limits the long cycling life. Here, we report a defective positive electrode material with a chemical formula of Na(3.2)□(0.8)Co(0.5)Fe(0.5)V(PO(3.9)F(0.1))(3) (□ represents Na...

CONCLUSIONS: Sarcopenia and depressive symptomatology are highly co-occurring in geriatric patients, and this association may be independent of frailty and comordibity burden.

Multiple myeloma (MM), an incurable malignancy of plasma cells, is predominantly an age-related disease, with the majority of cases occurring in patients over the age of 60. Cellular senescence, a fundamental biological process underlying aging, has been increasingly recognized for its critical role in developing age-related malignancies. In this study, we aimed to investigate the prognostic significance of genes implicated in the molecular mechanisms of senescence within a large cohort of MM...

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CONCLUSIONS: In conjunction with the analysis results from FGM(1,1) model and GRA of panel data, this study enhances the comprehensive understanding of the aging issue in Jiangsu Province. The insights derived herein offer crucial data support and a scientific foundation for both Jiangsu Province and the Chinese government to develop policies addressing population aging. Considering the anticipated future trends in aging, it is recommended that the government revise fertility policies to...

Background: Significant heterogeneity in individual responses to exercise interventions provides an opportunity to identify individuals for whom modifications or adjunct therapies may be necessary. Here, we explore heterogeneity of exercise response among people with HIV (PWH) versus without HIV (control). Methods: The Exercise for Healthy Aging Study enrolled sedentary older PWH and controls (50-75 years old) for a 24-week aerobic and resistance exercise program. Responder groups were...