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beta-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain

4 months 2 weeks ago
Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). We identify β-hydroxybutyrate (βHB), a ketone body, as a regulator of protein solubility. βHB primarily provides ATP substrate during periods of reduced glucose availability, and regulates other cellular processes through protein interactions. We demonstrate βHB-induced protein insolubility is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a...
Sidharth S Madhavan

Extracellular vesicle-packed microRNAs profiling in Alzheimer's disease: The molecular intermediary between pathology and diagnosis

4 months 2 weeks ago
MicroRNAs (miRNAs), referring to a type of non-coding RNAs functioning in various biological processes, participate in the pathophysiology of Alzheimer's disease (AD) through increasing amyloid-beta (Aβ) production, enhancing Tau phosphorylation, and inducing neuroinflammation. Meanwhile, extracellular vesicles (EVs) have been suggested as promising carriers of AD biomarkers as they possess the ability to transmit information from cerebral tissue to peripheral blood. Inspired by the above...
Sandila Arif

β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain

4 months 2 weeks ago
Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). We identify β-hydroxybutyrate (βHB), a ketone body, as a regulator of protein solubility. βHB primarily provides ATP substrate during periods of reduced glucose availability, and regulates other cellular processes through protein interactions. We demonstrate βHB-induced protein insolubility is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a...
Sidharth S Madhavan

Age-related clonal hematopoiesis and HIV infection are associated with geriatric outcomes: The ARCHIVE study

4 months 2 weeks ago
While HIV infection and clonal hematopoiesis (CH) have been linked with inflammatory dysregulation and an increased risk of aging-related comorbidities, their relationship with clinical geriatric syndromes has not been well defined. In the Age-related Clonal Haematopoiesis in an HIV Evaluation Cohort (ARCHIVE) study (NCT04641013), we measure associations between HIV and CH and geriatric syndromes. Of 345 participants (176 with HIV and 169 without HIV), 23% had at least one mutation associated...
Win Min Han

Discovering geroprotectors through the explainable artificial intelligence-based platform AgeXtend

4 months 2 weeks ago
Aging involves metabolic changes that lead to reduced cellular fitness, yet the role of many metabolites in aging is unclear. Understanding the mechanisms of known geroprotective molecules reveals insights into metabolic networks regulating aging and aids in identifying additional geroprotectors. Here we present AgeXtend, an artificial intelligence (AI)-based multimodal geroprotector prediction platform that leverages bioactivity data of known geroprotectors. AgeXtend encompasses modules that...
Sakshi Arora

Losartan attenuates sex-dependent hypertension, neuroinflammation, and cognitive impairment in the aging male sprague-dawley rat

4 months 2 weeks ago
The prevalence of hypertension increases with age and is the leading modifiable risk factor for cognitive impairment and dementia. At present, the neural mechanisms promoting hypertension across the lifespan are incompletely understood. Using the Sprague-Dawley (SD) rat as a model of normal aging, we hypothesized (1) blood brain barrier (BBB) disruption and neuroinflammation in the paraventricular nucleus (PVN) of the hypothalamus enhances sympathetic tone and contributes to age-dependent...
Kayla M Nist

A qualitative exploration of gaps in undergraduate gerontological nursing courses and recommendations for change

4 months 2 weeks ago
CONCLUSION: The inclusion of content such as spiritual needs and preventive healthcare services in undergraduate nursing curriculum is important in developing graduates that provide quality nursing care for older adults in Ghana. Additionally, the use of teaching approaches such as stand-alone courses, and clinical simulations can contribute significantly towards dispelling misconceptions about ageing and provide a deeper understanding of the care needs of older adults among nursing graduates in...
Confidence Alorse Atakro

Structural insights into the high basal activity and inverse agonism of the orphan receptor GPR6 implicated in Parkinson's disease

4 months 2 weeks ago
GPR6 is an orphan G protein-coupled receptor with high constitutive activity found in D2-type dopamine receptor-expressing medium spiny neurons of the striatopallidal pathway, which is aberrantly hyperactivated in Parkinson's disease. Here, we solved crystal structures of GPR6 without the addition of a ligand (a pseudo-apo state) and in complex with two inverse agonists, including CVN424, which improved motor symptoms in patients with Parkinson's disease in clinical trials. In addition, we...
Mahta Barekatain

TPR is required for cytoplasmic chromatin fragment formation during senescence

4 months 2 weeks ago
During oncogene-induced senescence there are striking changes in the organisation of heterochromatin in the nucleus. This is accompanied by activation of a pro-inflammatory gene expression programme - the senescence associated secretory phenotype (SASP) - driven by transcription factors such as NF-κB. The relationship between heterochromatin re-organisation and the SASP has been unclear. Here we show that TPR, a protein of the nuclear pore complex basket required for heterochromatin...
Bethany M Bartlett

Sympathetic motor neuron dysfunction is a missing link in age-associated sympathetic overactivity

4 months 2 weeks ago
Overactivity of the sympathetic nervous system is a hallmark of aging. The cellular mechanisms behind this overactivity remain poorly understood, with most attention paid to likely central nervous system components. In this work, we hypothesized that aging also affects the function of motor neurons in the peripheral sympathetic ganglia. To test this hypothesis, we compared the electrophysiological responses and ion-channel activity of neurons isolated from the superior cervical ganglia of young...
Lizbeth de La Cruz

Impact of Chinese visceral adiposity index on all-cause mortality risk in community-dwelling older adults: a prospective cohort study

4 months 2 weeks ago
CONCLUSION: Our study established a linear relationship between CVAI and mortality risk among community-dwelling older adults, with higher CVAI levels associated with a lower risk of all-cause mortality. These findings highlight the potential importance of visceral adiposity in predicting mortality risk in community-dwelling older adults.
Yuyu Zhang