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Reassignment letters come as reductions in force begin at NIH, FDA, and CDC

Research reveals how the key structural protein, inherently unstable at body temperature, forms resilient twists

CONCLUSIONS: Anti-Aβ mAb therapy slows cognitive decline, but with small effect sizes, and raises potential concerns about ARIA and headaches.

Drug repositioning or drug reprofiling, involves identifying novel indications for approved and previously abandoned drugs in the treatment of other diseases. The traditional drug discovery process is tedious, time-consuming, risky, and challenging. Fortunately, the inception of the drug repositioning concept has expedited the process by using compounds with established safety profiles in humans, and thereby significantly reducing costs. Alzheimer's disease (AD) is a severe neurological disorder...

Alzheimer's disease (AD) pathology includes transcriptional changes in the neurons, which are in part caused by the heterodimerization of two stress response transcription factors, CREB3L2 and ATF4. We investigated the role of proteasome inhibition and the eIF2α-kinase HRI in the formation of CREB3L2-ATF4 in neurons exposed to soluble oligomeric Aβ(42). While HRI activation increased ATF4 expression, it decreased CREB3L2 and CREB3L2-ATF4 levels. Proteasome inhibition, induced by Aβ(42), leads to...

Rates of cognitive decline in Alzheimer's disease (AD) are extremely heterogeneous. Although biomarkers for amyloid-beta (Aβ) and tau proteins, the hallmark AD pathologies, have improved pathology-based diagnosis, they explain only 20-40% of the variance in AD-related cognitive impairment (CI). To discover novel biomarkers of CI in AD, we performed cerebrospinal fluid (CSF) proteomics on 3,397 individuals from six major prospective AD case-control cohorts. Synapse proteins emerged as the...

Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer's disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here we present a new plasma tau species, the endogenously cleaved, microtubule-binding region containing residue 243 (eMTBR-tau243), which specifically...

Alzheimer disease (AD) therapy may benefit from optimized approaches to inhibit neuroinflammation. Small-molecule inhibitors of the proinflammatory molecule double-stranded RNA (dsRNA)-activated protein kinase R (PKR) have efficacy in AD models but their utility is compromised by adverse side effects. Here, we target PKR in two mouse models of AD using circular RNAs containing short double-stranded regions (ds-cRNAs), which are structurally similar to what we used previously to target PKR in...

The insulin-like growth factor-1 (IGF-1) signaling pathway is known as a potent aging modifier, disruption of which consistently associates with lifespan extension across diverse species. Despite this established association, the mechanisms by which IGF-1 signaling modulates organ aging remain poorly understood. In this study, we assessed age-related changes in IGF-1 expression across multiple organs in mice and identified a more prominent increase in skin IGF-1 levels with aging-a phenomenon...

CONCLUSION: This study showed a high prevalence of various factors related to physical function and cognitive impairment. The results revealed that comprehensive and systematic prevention and control programs for disabilities should be developed to improve the quality of life for older adults.

Life-history theory, central to our understanding of diversity in morphology, behaviour, and senescence, describes how traits evolve through the optimisation of trade-offs in investment. Despite considerable study, there is only minimal support for trade-offs within species between the two traits most closely linked to fitness - reproductive effort and survival - questioning the theory's general validity. We used a meta-analysis to separate the effects of individual quality (positive...

This study examines the long-term association between income and life expectancy in Sweden between 1960 and 2021. The study is based on register data that include all Swedish permanent residents aged 40 y and older. The results show that the gap in life expectancy between the top and bottom income percentiles widened substantially: For men, it increased from 3.5 y in the 1960s to 10.9 y by the 2010s, and for women, from 3.8 y in the 1970s to 8.6 y by the 2010s. Despite a reduction in income...

Splenic T cells are pivotal to the immune system, yet their function deteriorates with age. To elucidate the specific aspects of T cell biology affected by aging, we conducted a comprehensive multi-time point single-cell RNA sequencing study, complemented by single-cell Assay for Transposase Accessible Chromatin (ATAC) sequencing and single-cell T cell repertoire (TCR) sequencing on splenic T cells from mice across 10 different age groups. This map of age-related changes in the distribution of T...

CONCLUSIONS AND IMPLICATIONS: This scoping review revealed that eFIs can be developed using various electronic health care data sources, and they have been extensively employed for various population-level purposes. The observed associations between the eFIs, existing frailty assessment tools, and health outcomes highlight their utility in evaluating the care needs of an aging population.

Rates of cognitive decline in Alzheimer's disease (AD) are extremely heterogeneous. Although biomarkers for amyloid-beta (Aβ) and tau proteins, the hallmark AD pathologies, have improved pathology-based diagnosis, they explain only 20-40% of the variance in AD-related cognitive impairment (CI). To discover novel biomarkers of CI in AD, we performed cerebrospinal fluid (CSF) proteomics on 3,397 individuals from six major prospective AD case-control cohorts. Synapse proteins emerged as the...

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Oligodendrocyte progenitor cells (OPCs) are highly dynamic, widely distributed glial cells of the central nervous system responsible for generating myelinating oligodendrocytes throughout life. However, the rates of OPC proliferation and differentiation decline dramatically with aging, which may impair homeostasis, remyelination and adaptive myelination during learning. To determine how aging influences OPCs, we generated a transgenic mouse line (Matn4-mEGFP) and performed single-cell RNA...

Cardiac aging is an intrinsic process that leads to impaired heart function, along with cellular and molecular changes. Recent research highlights the important role of mitochondria in cardiac function, due to the heart's high energy demands. Serum response factor (SRF), a transcription factor involved in regulating actin and smooth muscle gene expression, is well known as a regulator of various aspects of cardiac function. However, its role in mitochondrial regulation and cardiac aging is...

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