Endocytosis and Alzheimer ’s disease
AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative disorder and is the most common cause of dementia. The pathogenesis of AD still remains unclear, including two main hypotheses: amyloid cascade and tau hyperphosphorylation. The hallmark neuropathological changes of AD are extracellular deposits o f amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Endocytosis plays an important role in a number of cellular processes including communication with the extracellular environment, nutrient uptake, and signaling by the cell surface receptors. Based on the results of genet ic and bioc...
Source: AGE - August 30, 2023 Category: Geriatrics Source Type: research
Elimination of senescent cells by treatment with Navitoclax/ABT263 reverses whole brain irradiation-induced blood-brain barrier disruption in the mouse brain
In this study, we aimed to test the hypothesis that WBI induces endothelial senescence, contributing to chronic disruption of the blood-brain barrier (BBB) and microvascular rarefaction. To accomplish this, we utilized transgenic p16-3MR mice, which enable the identification and selective elimination of senescent cells. These mice were subjected to a clinically relevant fractionated WBI protocol (5 Gy twice weekly for 4 weeks), and cranial windows were applied to both WBI-treated and control mice. Quantitative assessment of BBB permeability and capillary density was performed using two-photon microscopy at the 6-month post...
Source: AGE - August 29, 2023 Category: Geriatrics Source Type: research
In-vivo screening implicates endoribonuclease Regnase-1 in modulating senescence-associated lysosomal changes
AbstractAccumulation of senescent cells accelerates aging and age-related diseases, whereas preventing this accumulation extends the lifespan in mice. A characteristic of senescent cells is increased staining with β-galactosidase (β-gal) ex vivo. Here, we describe a progressive accumulation of β-gal staining in the model organismC. elegans during aging. We show that distinct pharmacological and genetic interventions targeting the mitochondria and the mTORC1 to the nuclear core complex axis, the non-canonical apoptotic, and lysosomal-autophagy pathways slow the age-dependent accumulation of β-gal. We identify a novel ge...
Source: AGE - August 29, 2023 Category: Geriatrics Source Type: research
Elimination of senescent cells by treatment with Navitoclax/ABT263 reverses whole brain irradiation-induced blood-brain barrier disruption in the mouse brain
In this study, we aimed to test the hypothesis that WBI induces endothelial senescence, contributing to chronic disruption of the blood-brain barrier (BBB) and microvascular rarefaction. To accomplish this, we utilized transgenic p16-3MR mice, which enable the identification and selective elimination of senescent cells. These mice were subjected to a clinically relevant fractionated WBI protocol (5 Gy twice weekly for 4 weeks), and cranial windows were applied to both WBI-treated and control mice. Quantitative assessment of BBB permeability and capillary density was performed using two-photon microscopy at the 6-month post...
Source: AGE - August 29, 2023 Category: Geriatrics Source Type: research
Serum methylmalonic acid concentrations at breast cancer diagnosis significantly correlate with clinical frailty
This study investigates the potential of serum MMA concentrations as a biomarker for age-related clinical frailty in older patients with breast cancer. One hundred nineteen patients ≥ 70 years old with early-stage breast cancer were included (median age 76 years). G8 screening, full geriatric assessment, clinical parameters (i.e., estimated glomerular filtration rate (eGFR) and body mass index (BMI)), and serum sample collection were collected at breast cancer diagnosi s before any therapy was administered. MMA concentrations were measured via liquid chromatography with tandem mass spectrometry. MMA concentrations...
Source: AGE - August 26, 2023 Category: Geriatrics Source Type: research
Association between aging-related biomarkers and longitudinal trajectories of intrinsic capacity in older adults
AbstractIntrinsic capacity (IC), the composite of physical and mental capacities, declines with age at different rates and patterns between individuals. We aimed to investigate the association between longitudinal IC trajectories and plasma biomarkers of two hallmarks of aging —chronic inflammation and mitochondrial dysfunction—in older adults. From the Multidomain Alzheimer Preventive Trial (MAPT), we included 1271 community-dwelling older people (mean [SD] age = 76.0 [4.3] years) with IC data over four years. Group-based multi-trajectory modeling was performed to id entify clusters of the participants with similar lo...
Source: AGE - August 24, 2023 Category: Geriatrics Source Type: research
Signs of aging in midlife: physical function and sex differences in microbiota
AbstractMicrobiota composition has been linked to physical activity, health measures, and biological age, but a shared profile has yet to be shown. The aim of this study was to examine the associations between microbiota composition and measures of function, such as a composite measure of physical capacity, and biological age in midlife, prior to onset of age-related diseases. Seventy healthy midlife individuals (age 44.58 ± 0.18) were examined cross-sectionally, and their gut-microbiota profile was characterized from stool samples using 16SrRNA gene sequencing. Biological age was measured using the Klemera-Doubal me...
Source: AGE - August 23, 2023 Category: Geriatrics Source Type: research
Sex-dependent associations of plasma high-density lipoprotein cholesterol and mortality risk in healthy older men and women: two prospective cohort studies
This study examined the associations between HDL-C levels and mortality in initially healthy older men and women. This analysis included participants from the Aspirin in Reducing Events in the Elderly (ASPREE;n=18,668) trial and a matched cohort from the UK Biobank (UKB;n=62,849 ≥65 years). Cox regression was used to examine hazard ratios between HDL-C categories<1.03 mmol/L, 1.03 –1.55 mmol/L (referent category), 1.55–2.07 mmol/L, and>2.07 mmol/L and all-cause, cancer, cardiovascular disease (CVD), and “non-cancer non-CVD” mortality. Genetic contributions were assessed using a polygenic score for HDL-C. Am...
Source: AGE - August 23, 2023 Category: Geriatrics Source Type: research
Glucose metabolism in posterior cingulate cortex has supplementary value to predict the progression of cognitively unimpaired to dementia due to Alzheimer ’s disease: an exploratory study of 18F-FDG-PET
AbstractAmyloid- β (Aβ) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer’s disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer’s Association (NIA-AA). However, it is clinically diffic ult to predict those subjects who were already with Aβ positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevent ion of AD. ...
Source: AGE - August 23, 2023 Category: Geriatrics Source Type: research
Signs of aging in midlife: physical function and sex differences in microbiota
AbstractMicrobiota composition has been linked to physical activity, health measures, and biological age, but a shared profile has yet to be shown. The aim of this study was to examine the associations between microbiota composition and measures of function, such as a composite measure of physical capacity, and biological age in midlife, prior to onset of age-related diseases. Seventy healthy midlife individuals (age 44.58 ± 0.18) were examined cross-sectionally, and their gut-microbiota profile was characterized from stool samples using 16SrRNA gene sequencing. Biological age was measured using the Klemera-Doubal me...
Source: AGE - August 23, 2023 Category: Geriatrics Source Type: research
Sex-dependent associations of plasma high-density lipoprotein cholesterol and mortality risk in healthy older men and women: two prospective cohort studies
This study examined the associations between HDL-C levels and mortality in initially healthy older men and women. This analysis included participants from the Aspirin in Reducing Events in the Elderly (ASPREE;n=18,668) trial and a matched cohort from the UK Biobank (UKB;n=62,849 ≥65 years). Cox regression was used to examine hazard ratios between HDL-C categories<1.03 mmol/L, 1.03 –1.55 mmol/L (referent category), 1.55–2.07 mmol/L, and>2.07 mmol/L and all-cause, cancer, cardiovascular disease (CVD), and “non-cancer non-CVD” mortality. Genetic contributions were assessed using a polygenic score for HDL-C. Am...
Source: AGE - August 23, 2023 Category: Geriatrics Source Type: research
