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CONCLUSION: The current investigation unveiled that PNI has emerged as an autonomous determinant for both short-and long-term mortality in older adults receiving CABG.

CONCLUSIONS: All VI measures predicted faster declines in SPPB. Older adults with VI may benefit from targeted intervention to prevent declines in mobility.

CONCLUSIONS: Despite inadequate knowledge and limited experience in frailty management, clinical nurses' attitudes towards frailty management were positive, indicating potential for improvement. The model was useful to explain practices in frailty management, thereby providing a theoretical basis for development of targeted training programs.

Geroscience has helped to usher in a new and exciting era of aging drug development and evaluation of novel and repurposed agents, as well as natural compounds purported to target one or more aging hallmarks. Among the latter, curcumin has long been pursued as a promising strategy but has failed to provide convincing evidence in human trials. Oral intake is the typical route of administration tested for the vast majority of gerotherapeutic candidates, including curcumin, but efficacy is...

Europe is experiencing a significant demographic shift, with aging populations posing economic and social challenges due to increased healthcare costs and a higher prevalence of age-related diseases. Hungary, in particular, faces these challenges acutely due to higher morbidity and mortality rates from a range of chronic age-related diseases and behavioral risk factors. Addressing these issues requires innovative approaches to promote healthy aging. Semmelweis University, the largest healthcare...

New studies of Apollo rocks push the Moon's formation back more than 100 million years

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Small molecules that can reduce the neurotoxic beta-amyloid (Aβ) aggregates in the brain provide a potential treatment for Alzheimer disease (AD). Most screening methods for small-molecule hits focus on the overall Aβ aggregations without a specific target, such as the very first association step (i.e., nucleation) en route to the Aβ oligomers. Located in the middle of a full-length Aβ peptide, Aβ(19-20) (diphenylalanine or FF) nucleates the neurotoxic Aβ oligomer formation. Here, we innovate a...

Alzheimer's disease (AD) is caused by the assembly of amyloid-beta (Aβ) peptides into oligomers and fibrils. Endogenous Aβ aggregation may be assisted by cell membranes, which can accelerate the nucleation step enormously, but knowledge of membrane-assisted aggregation is still very limited. Here, we used extensive molecular dynamics (MD) simulations to structurally and energetically characterize key intermediates along the membrane-assisted aggregation pathways of Aβ40. Reinforcing experimental...

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We leverage a clinical trial (NCT04080804) that compared neoadjuvant anti-PD-1, anti-PD-1+CTLA-4, and anti-PD-1+LAG-3 therapies in head and neck squamous cell carcinoma patients. Combination therapies promote higher pathologic response rates versus monotherapy, and major pathologic response is associated with better survival. To address whether successful immune checkpoint inhibitor (ICI) regimens act through similar or distinct pathways, we robustly and longitudinally characterize...

In primary age-related tauopathy (PART) and Alzheimer's disease (AD), tau aggregates share a similar structure and anatomic distribution, which is distinct from tau pathology in other diseases. However, transcriptional similarities between PART and AD and gene expression changes within tau-pathology-bearing neurons are largely unknown. Using GeoMx spatial transcriptomics, mRNA was quantified in hippocampal neurons with and without tau pathology in PART and AD. Synaptic genes were down-regulated...

Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however, few studies have investigated its role in neurodegenerative processes such as Alzheimer's disease (AD). Here, we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated...

Microelectrode arrays (MEAs) permit recordings with high electrode counts, thus generating complex datasets that would benefit from precise neuronal spike sorting for meaningful data extraction. Nevertheless, conventional spike sorting methods face limitations in recognizing diverse spike shapes. Here, we introduce PseudoSorter, which uses self-supervised learning techniques, a density-based pseudolabeling strategy, and an iterative fine-tuning process to enhance spike sorting accuracy. Through...

White-matter diseases like multiple sclerosis begin in young adulthood. Aging, being a risk factor, contributes to the progression of these diseases and makes neurological disabilities worsen. Aging causes white matter alteration due to myelin loss, axonal degeneration, and hyperintensities, resulting in cognitive impairment and neurological disorders. Aging also negatively affects central nervous system resident glial cells and peripheral immune cells, contributing to myelin degeneration and...

Neuroinflammaging is the nervous system version of inflammaging, the low-grade inflammation that develops with advanced age, aside from active disease or infection. Despite neuroinflammaging has been widely investigated, some important issues still need to be resolved such as the analysis of the extremely old subjects and the evaluation of specific brain areas. On this background, we conducted a study to analyze expression of inflammatory and anti-inflammatory genes in Wistar rats of different...

The orexinergic system is anatomically and functionally conserved in almost all vertebrates, and the role in healthy ageing and age-associated diseases has been studied in mammals. Here, we review the main findings on the age-related regulation of orexinergic system in mammals, including human patients and highlights how the fish Nothobranchius furzeri serves as an exceptional model to spearhead research and unravel the intricate mechanisms underlying orexinergic regulation during ageing. The...

To check whether the reported waves of age-dependent changes in multiomics patterns in humans influence age-specific mortality, life-table aging rate (LAR) trajectories derived from Human Morality Database (HMD) data were modeled based on assumptions inherent in a generalized Gompertz-Makeham Law (gGML). The gGML implies that any changes in resistance to causes of death (CoD) and in exposure to CoD are translated into changes in mortality in an exponential and a linear way, respectively....

Aged-related cognitive impairments are associated with molecular neurodegenerations and impeded neurogenesis in the dentate gyrus (DG) of the damaged hippocampus. Neurogenesis requires activated cyclic AMP-responsive element-binding protein (CREB) pathway to enhance neuronal development, synaptic plasticity, cognition, learning and memory. Current research has reported that consecutive administration of D-galactose can accelerate brain aging by inducing oxidation and inflammation. The flavonoid...

Aging is a major risk factor for disease, and developing effective pharmaceutical interventions to improve healthspan and promote longevity has become a high priority for society. One of the molecular pathways related to longevity in various model organisms revolves around lowering AKT1 levels. This prompted our in silico drug screen for small molecules capable of mimicking the transcriptional effects of AKT1 knockdown. We found topoisomerase inhibitors as a top candidate longevity-drug class....