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Discovering geroprotectors through the explainable artificial intelligence-based platform AgeXtend
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...
Daily briefing: How to get to 100 - centenarian cells teach us about ageing
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What is ageing? Even the field's researchers can't agree
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Losartan attenuates sex-dependent hypertension, neuroinflammation, and cognitive impairment in the aging male sprague-dawley rat
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...
A qualitative exploration of gaps in undergraduate gerontological nursing courses and recommendations for change
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...
Structural insights into the high basal activity and inverse agonism of the orphan receptor GPR6 implicated in Parkinson's disease
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...
TPR is required for cytoplasmic chromatin fragment formation during senescence
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...
Sympathetic motor neuron dysfunction is a missing link in age-associated sympathetic overactivity
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...
Impact of Chinese visceral adiposity index on all-cause mortality risk in community-dwelling older adults: a prospective cohort study
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.
Frailty phenotypes and their association with health consequences: a comparison of different measures
CONCLUSION: The proposed frailty phenotype classification differs from the existing frailty measures in its ability to distinguish the corresponding phenotypes underlying various health consequences. Governments may develop strategies based on frailty phenotypes to mitigate adverse health consequences.
Association of subjective memory complaints with serum biomarkers of neurodegeneration and cognition: A population-based study
CONCLUSIONS: Individuals who reported more memory complaints had higher levels of biomarkers of neurodegeneration and a faster rate of cognitive decline, suggesting that SMCs may be valuable for identifying people at high risk of cognitive impairment.
Baboons, bacteria, and biological clocks address an age-old question
Studying the fecal microbiota of wild baboons helps provide new insight into the factors that influence biological aging.