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Defective ion channel turnover and clearance of damaged proteins are associated with aging and neurodegeneration. The L-type Ca(V)1.2 voltage-gated calcium channel mediates depolarization-induced calcium signals in heart and brain. Here, we determined the interaction surface between actin and two calcium channel subunits, Ca(V)β(2) and Ca(V)β(4), using cross-linking mass spectrometry and protein-protein docking, and uncovered a role in replenishing conduction-defective Ca(V)1.2 channels....

Cellular senescence is the permanent cessation of cell proliferation and growth. Senescent cells accumulating in tissues and organs with aging contribute to many chronic diseases, mainly through the secretion of a pro-inflammatory senescence-associated secretory phenotype (SASP). Senotherapeutic (senolytic or senomorphic) strategies targeting senescent cells or/and their SASP are being developed to prolong healthy lifespan and treat age-related pathologies. Sodium-glucose co-transporter 2...

CONCLUSION: The ToC is effective in identifying key characteristics of resources, interventions, impact, and outcomes of integrated care for OP. Our ICOPE program has been strengthened by ToC, which forms an integrated care model for assessment, planning, implementation, and evaluation, adapted to a specific setting, and provides guidance for other areas in similar settings.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. Metabolic dysfunctions, particularly type 2 diabetes mellitus (T2DM), have been implicated in AD pathogenesis, highlighting the potential for novel therapeutic approaches targeting shared underlying mechanisms. Here, we investigate sodium-glucose cotransporter 2 (SGLT2) inhibition as a therapeutic strategy for AD using Enavogliflozin, a potent SGLT2 inhibitor, in the 5XFAD mouse model....

CONCLUSION: The AMS was developed to identify older adults with PCML. The reliability and validity of the AMS and its interpretation strategies will be evaluated as the screening protocol is piloted.

Word-finding difficulty is a common challenge in older age and is linked to various neuropathological conditions associated with ageing. Transcranial direct current stimulation (tDCS) has shown promise as a cognitive enhancement tool for both healthy aging and age- related cognitive disorders. However, its effectiveness in enhancing word-finding ability remains inconsistent, especially among healthy adults. Variability across studies is likely due to factors such as task selection, stimulation...

CONCLUSIONS: Men and later-born cohorts experienced significantly better mental and cognitive health than women and earlier-born cohorts. Age- and gender-related changes in mental and cognitive health in later life should be considered within the socio-culturally contextualized birth cohort.

Aging is accompanied by widespread DNA methylation changes across the genome. While age-related methylation studies typically focus on individual CpGs, cluster analysis provides more robust data and improved interpretation. We characterized age-associated CpG-cluster methylation changes in mouse spleens, peripheral blood mononuclear cells, and livers. We identified a novel signature termed blanket methylations (BMs), fully methylated CpG clusters absent in young tissues but appearing in aged...

Appetite loss is a common clinical condition in older adulthood, but how this condition associates with biological aging remains unknown. The present study aims to examine the associations of biological aging markers with appetite loss in community-dwelling people aged 21 to 102 years. This retrospective case-control study used baseline data from the INSPIRE-T cohort in Toulouse, France. Each of the 49 cases with appetite loss was sex- and age-matched to two controls without appetite loss (n =...

Behavior is more complex than scientists realized, could reveal origins of musicality

Alzheimer's disease (AD) is initiated by amyloid-beta (Aβ) accumulation in the neocortex; however, the cortical layers and neuronal cell types first susceptible to Aβ remain unknown. Using in vivo two-photon Ca^(2+) imaging in the visual cortex of AD mouse models, we found that cortical layer 5 neurons displayed abnormally prolonged Ca^(2+) transients before substantial plaque formation. Neuropixels recordings revealed that these abnormal transients were associated with reduced spiking and...

The onset of Alzheimer's Disease and Frontotemporal Dementia is closely associated with the aggregation of tau, a multifunctional protein essential for neuronal stability and function. Given the role of tau aggregation in neurodegeneration, understanding the mechanisms behind its fibril formation is crucial for developing therapeutic interventions to halt or reverse disease progression. However, the structural complexity and diverse aggregation pathways of tau present significant challenges,...

Computational research tools have reached a level of maturity that enables efficient simulation of neural activity across diverse scales. Concurrently, experimental neuroscience is experiencing an unprecedented scale of data generation. Despite these advancements, our understanding of the precise mechanistic relationship between neural recordings and key aspects of neural activity remains insufficient, including which specific features of electrophysiological population dynamics (i.e., putative...

The recent emergence of wearable devices will enable large scale remote brain monitoring. This study investigated whether multimodal wearable sleep recordings could help screening for Alzheimer's disease (AD). Measurements were acquired simultaneously from polysomnography and a wearable device, measuring electroencephalography (EEG) and accelerometry (ACM) in 67 elderly without cognitive symptoms and 35 AD patients. Sleep staging was performed using an AI model (SeqSleepNet), followed by feature...

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Pathophysiological mechanisms underlying hematoma expansion in spontaneous intracerebral hemorrhage (ICH) remain poorly understood, and most data are derived from postmortem studies or serial neuroimaging studies performed over hours to days from onset. Our unique case report of a hypertensive ICH serendipitously captured by serial CT provides valuable in vivo data from the very onset of hematoma formation in an aging individual. A 76-year-old hypertensive man underwent elective carotid CT...

CONCLUSION: We found that a large proportion of caregiving relationships were best described as a network that frequently included multiple caregivers, multiple care receivers, and some in both roles, as well as non-kin and extended relative participants. This characterization of care relationships allows us to better understand the needs of older adults and their caregivers as the population ages and care shifts towards aging-in-place strategies.

Implicit Motor Sequence Learning (IMSL) is critical for automating motor skills, yet it declines with age, impacting independence and quality of life. This study investigated the age-specific roles of the primary motor cortex (M1) and supplementary motor area (SMA) in IMSL using a novel concurrent transcranial direct current stimulation (tDCS) and functional near-infrared spectroscopy (fNIRS) approach. Twenty younger adults (21-32 years old [M = 24.3 ± 3.26]) and twenty older adults (60-76 years...

Parkinson's disease (PD) is thought to develop through a complex interplay of genetic and environmental factors. Epidemiological studies have linked exposure to certain pesticides such as paraquat with elevated PD risk, although how a person's genetic makeup influences disease risk upon exposure remains unknown. Here, we used a genome-wide approach to uncover genes that play a role in resistance to paraquat-induced dopaminergic neurodegeneration in Drosophila. We developed a paraquat exposure...