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Neuroimaging and biofluid biomarkers across race and ethnicity in older adults across the spectrum of cognition
Neuroimaging and biofluid biomarkers provide a proxy of pathological changes for Alzheimer's disease (AD) and are useful in improving diagnosis and assessing disease progression. However, it is not clear how race/ethnicity and different prevalence of AD risks impact biomarker levels. In this narrative review, we survey studies focusing on comparing biomarker differences between non-Hispanic White American(s) (NHW), African American(s) (AA), Hispanic/Latino American(s) (HLA), and Asian...
Liver X receptor alpha contribution to neuroinflammation and glial cells activation induced by MPTP: Implications for Parkinson's disease
Parkinson's disease (PD) is the second most common neurodegenerative disorder whose etiology remains unknown. The immune system has been implicated in hallmarks of PD including aggregation of α-synuclein and death of dopaminergic neurons in the substantia nigra. As a core regulator of immune response and inflammation, liver X receptors (LXRs) have been shown to have protective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. With two isoforms of LXRs...
Scientists are building giant ‘evidence banks’ to create policies that actually work
Hopes of new physics dashed with measurement of hefty particle’s mass
The W boson has precisely the mass predicted by physicists’ standard model
2'-Fucosyllactose attenuates aging-related metabolic disorders through modulating gut microbiome-T cell axis
Aging-related metabolic disorders seriously affect the lifespan of middle-aged and older people, potentially due to disruptions in the adaptive immune and gut microbial profiles. Dietary intervention offers a promising strategy for maintaining metabolic health. This study aimed to investigate the ameliorative effect of 2'-fucosyllactose (2'-FL) on aging-induced metabolic dysfunction and the underlying mechanisms. The results revealed that 2'-FL significantly relieved aging-related metabolic...
Associations of nighttime sleep, midday napping, and physical activity with all-cause mortality in older adults: the Seniors-ENRICA cohorts
We examined associations between nighttime sleep and midday nap duration with all-cause mortality according to adherence to moderate-to-vigorous physical activity (MVPA) recommendations in older adults. We used data from 3518 and 3273 older adults recruited in the Seniors-ENRICA-1 and 2 cohorts, respectively. Nighttime sleep time was classified as short (< 7 h), middle (≥ 7 and < 8 h), and long (≥ 8 h), and midday napping as no nap, short (≤ 30 min), long (> 30 and ≤ 60 min), and very long (> 60...
Loss of SELENOW aggravates muscle loss with regulation of protein synthesis and the ubiquitin-proteasome system
Sarcopenia is characterized by accelerated muscle mass and function loss, which burdens and challenges public health worldwide. Several studies indicated that selenium deficiency is associated with sarcopenia; however, the specific mechanism remains unclear. Here, we demonstrated that selenoprotein W (SELENOW) containing selenium in the form of selenocysteine functioned in sarcopenia. SELENOW expression is up-regulated in dexamethasone (DEX)-induced muscle atrophy and age-related sarcopenia...
Causal associations and shared genetic etiology of neurodegenerative diseases with epigenetic aging and human longevity
The causative mechanisms underlying the genetic relationships of neurodegenerative diseases with epigenetic aging and human longevity remain obscure. We aimed to detect causal associations and shared genetic etiology of neurodegenerative diseases with epigenetic aging and human longevity. We obtained large-scale genome-wide association study summary statistics data for four measures of epigenetic age (GrimAge, PhenoAge, IEAA, and HannumAge) (N = 34,710), multivariate longevity (healthspan,...
CRISPR-Cas9 mediated d3GHR knockout in HEK293 cells: Revealing the longevity associated isoform stress resilience
The Growth Hormone Receptor (GHR) gene encodes a protein that is essential for mediating the biological effects of growth hormone (GH). A series of molecular events are set off when GH binds to its receptor, resulting in a variety of physiological reactions linked to development, growth, and metabolism. Recently a particular genetic variation, within the GHR gene that is labeled as the "d3GHR," which lacks exon 3 was associated with longevity. This specific deletion isoform was connected to...
Defining an ageing-related pathology, disease or syndrome: International Consensus Statement
Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand...
The extent and burden of high multimorbidity on older adults in the US: a descriptive analysis of Medicare beneficiaries
CONCLUSIONS: The development and progression of multimorbidity in old age is influenced by many factors. Higher levels of multimorbidity are associated with sociodemographic characteristics, suggesting possible mitigation strategies.
Age-related changes in sleep spindle characteristics in individuals over 75 years of age: a retrospective and comparative study
CONCLUSION: We observed the same sleep spindle characteristics in both age groups except for localization. We built our study on a short sample, and participants were not free of all sleep disorders. We could establish normative values through further studies with larger samples of people without any sleep disorders to understand the modifications in normal aging and pathological conditions and to reveal the predictive biomarker function of sleep spindles.
A pontine-medullary loop crucial for REM sleep and its deficit in Parkinson's disease
Identifying the properties of the rapid eye movement (REM) sleep circuitry and its relation to diseases has been challenging due to the neuronal heterogeneity of the brainstem. Here, we show in mice that neurons in the pontine sublaterodorsal tegmentum (SubLDT) that express corticotropin-releasing hormone-binding protein (Crhbp^(+) neurons) and project to the medulla promote REM sleep. Within the medullary area receiving projections from Crhbp^(+) neurons, neurons expressing nitric oxide...
Glucocorticoids induce HMGB1 release in primary cultured rat cortical microglia
Stress, a risk factor for major depressive disorder and Alzheimer disease, leads to the release of high-mobility group box-1 (HMGB1) protein, which in turn causes neuroinflammation. The mechanism underlying stress-induced HMGB1 release is unknown, but stress-associated glucocorticoids could be involved. Primary cultured rat cortical microglia and neurons were treated with corticosterone, a stress-associated glucocorticoid, and HMGB1 release was measured by ELISA and western blotting to test this...
CYP1B1-RMDN2 Alzheimer's disease endophenotype locus identified for cerebral tau PET
Determining the genetic architecture of Alzheimer's disease pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we perform a genome-wide association study of cortical tau quantified by positron emission tomography in 3046 participants from 12 independent studies. The CYP1B1-RMDN2 locus is associated with tau deposition. The most significant signal is at rs2113389, explaining 4.3% of the variation in cortical tau, while APOE4 rs429358 accounts for...
Meta-analysis of the make-up and properties of in vitro models of the healthy and diseased blood-brain barrier
In vitro models of the human blood-brain barrier (BBB) are increasingly used to develop therapeutics that can cross the BBB for treating diseases of the central nervous system. Here we report a meta-analysis of the make-up and properties of transwell and microfluidic models of the healthy BBB and of BBBs in glioblastoma, Alzheimer's disease, Parkinson's disease and inflammatory diseases. We found that the type of model, the culture method (static or dynamic), the cell types and cell ratios, and...
Serum protein patterns are associated with future diagnosis of Alzheimer's disease
No abstract
Causal associations and shared genetic etiology of neurodegenerative diseases with epigenetic aging and human longevity
The causative mechanisms underlying the genetic relationships of neurodegenerative diseases with epigenetic aging and human longevity remain obscure. We aimed to detect causal associations and shared genetic etiology of neurodegenerative diseases with epigenetic aging and human longevity. We obtained large-scale genome-wide association study summary statistics data for four measures of epigenetic age (GrimAge, PhenoAge, IEAA, and HannumAge) (N = 34,710), multivariate longevity (healthspan,...