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The APOE isoforms differentially shape the transcriptomic and epigenomic landscapes of human microglia xenografted into a mouse model of Alzheimer's disease

1 week 5 days ago
Microglia play a key role in the response to amyloid beta in Alzheimer's disease (AD). In this context, the major transcriptional response of microglia is the upregulation of APOE, the strongest late-onset AD risk gene. Of its three isoforms, APOE2 is thought to be protective, while APOE4 increases AD risk. We hypothesised that the isoforms change gene regulatory patterns that link back to biological function by shaping microglial transcriptomic and chromatin landscapes. We use RNA- and...
Kitty B Murphy

Whole-genome sequencing analyses suggest novel genetic factors associated with Alzheimer's disease and a cumulative effects model for risk liability

1 week 5 days ago
Genome-wide association studies (GWAS) on Alzheimer's disease (AD) have predominantly focused on identifying common variants in Europeans. Here, we performed whole-genome sequencing (WGS) of 1,559 individuals from a Korean AD cohort to identify various genetic variants and biomarkers associated with AD. Our GWAS analysis identified a previously unreported locus for common variants (APCDD1) associated with AD. Our WGS analysis was extended to explore the less-characterized genetic factors...
Jun Pyo Kim

Psychological effects of mountainous environments over the life span and potential implications for healthy ageing: A narrative review

1 week 5 days ago
BACKGROUND: Healthy ageing is defined as a process of preserving functional capacity to enable well-being in old age. This concept includes both a physical and a psychological component, which can be positively influenced by spending time in nature and being physically active. Mountainous areas offer diverse opportunities to be physically active in a natural environment. However, little research is available on the psychological effects of mountain environments and mountain sports, particularly...
Benedikt Hösl

Integrated multi-omics analysis reveals immunovascular mechanisms of the placenta-maternal brain axis and lifespan neurobehavior changes in a mouse model of preeclampsia

1 week 5 days ago
Preeclampsia (PE) is a hypertensive disorder of pregnancy, among the leading global drivers of maternal morbidity. PE can precipitate neuropsychiatric risk, including for peripartum anxiety, depression, and cognitive problems. To investigate mechanisms underlying psycho-obstetric risk in PE, we examined maternal metabolic, placental, brain, and behavioral changes in our chronic vasopressin (AVP) infusion PE mouse model (C57Bl6/J). Elevated maternal AVP secretion predicts PE in humans, and...
Serena Gumusoglu

ElixirSeeker: A Machine Learning Framework Utilizing Fusion Molecular Fingerprints for the Discovery of Lifespan-Extending Compounds

1 week 5 days ago
Despite the growing interest in developing anti-aging drugs, high costs and low success rates of traditional drug discovery methods pose significant challenges. Aging is a complex biological process associated with numerous diseases, making the identification of compounds that can modulate aging mechanisms critically important. Accelerating the discovery of potential anti-aging compounds is essential to overcome these barriers and enhance lifespan and healthspan. Here, we present ElixirSeeker, a...
Yan Pan

Multi-organ metabolome biological age implicates cardiometabolic conditions and mortality risk

1 week 5 days ago
Multi-organ biological aging clocks across different organ systems have been shown to predict human disease and mortality. Here, we extend this multi-organ framework to plasma metabolomics, developing five organ-specific metabolome-based biological age gaps (MetBAGs) using 107 plasma non-derivatized metabolites from 274,247 UK Biobank participants. Our age prediction models achieve a mean absolute error of approximately 6 years (0.25
MULTI consortium

Acetylation profiling by Iseq-Kac reveals insights into HSC aging and lineage decision

1 week 5 days ago
Profiling post-translational modifications face challenges with low-input samples. We developed Iseq-Kac (internal standard-assisted enrichment-free approach for high-throughput quantitative analysis of lysine acetylation) to profile the acetylome in as few as 10³-10⁴ cells. By using a hyperacetylated internal standard, Iseq-Kac can be used in mass spectrometry (MS) to enhance MS1 signals and facilitate MS2 fragmentation of acetylated peptides. Using Iseq-Kac, we quantified 675-1,471 acetylated...
Yanqiu Gong

Pace of Aging analysis of healthspan and lifespan in older adults in the US and UK

1 week 5 days ago
As societies age, policy makers need tools to understand how demographic aging will affect population health and to develop programs to increase healthspan. The current metrics used for policy do not distinguish differences caused by early-life factors, like prenatal care and nutrition, from those caused by ongoing changes in people's bodies that are due to aging and that may be modifiable. Here we introduce an adapted Pace of Aging method designed to quantify differences between individuals and...
Arun Balachandran

Accumulation of GSK-3β in Interneurons Impairs Adult Hippocampal Neurogenesis by Inhibiting GABAergic Transmission

1 week 5 days ago
The activation of glycogen synthase kinase 3β (GSK-3β) and the deterioration of spatial memory represent prominent pathological and clinical manifestations of Alzheimer's disease (AD). Nevertheless, the precise intrinsic mechanisms linking these pathological features remain poorly elucidated. In this study, we identified significant upregulation of GSK-3β activity in inhibitory interneurons within the hippocampal dentate gyrus (DG) of 3×Tg-AD mice. Subsequent investigations demonstrated that...
Fei Liu

Effects of cannabidiol (CBD) treatment on age-related cognitive decline in C57 mice

1 week 5 days ago
Aging is associated with cognitive decline, and currently, there are no approved medications that can prevent these impairments. Recently, cannabinoids derived from Cannabis sativa have emerged as promising therapeutic compounds with neuroprotective, anti-inflammatory, and cognitive-enhancing properties. Despite their benefits, further research is needed to fully understand their efficacy across various conditions. This study investigates the effects of cannabidiol (CBD) on memory impairment and...
Behroo Mirza Agha

Vascular senescence and aging: mechanisms, clinical implications, and therapeutic prospects

1 week 5 days ago
The aging vasculature is characterized by endothelial dysfunction, arterial stiffness, and increased susceptibility to vascular pathologies. Central to these changes is the process of cellular senescence, where endothelial and vascular smooth muscle cells lose their replicative and functional capacity and adopt a pro-inflammatory secretory phenotype. This review provides an overview of the key mechanisms underlying vascular senescence, including the p53/p21 and p16/Rb pathways, the...
Aitor Picos

Bidirectional upregulation of Klotho by triiodothyronine and baicalein: mitigating chronic kidney disease and associated complications in aged BALB/c mice

1 week 5 days ago
Chronic kidney disease (CKD) is a global health challenge marked by progressive renal decline and increased mortality. The interplay between CKD and hypothyroidism, particularly nonthyroidal low-triiodothyronine (T3) syndrome, exacerbates disease progression, driven by HPT axis dysfunction and reduced Klotho levels due to the Wnt/β-catenin pathway activation. This study explored Klotho as a link between CKD and hypothyroidism using an adenine-induced CKD aged mouse model. Exogenous T3 and...
Saswat Kumar Mohanty

Reproduction and preference to macronutrients have different relations to biological or chronological age in Drosophila

1 week 5 days ago
Varied factors and interventions were shown to extend the lifespan. An understanding of the mechanisms behind the beneficial effects might extend our understanding of how interventions work. However, in most studies, groups are compared at distinct time points representing chronological age. This setup does not take into account that organisms of the same chronological age are different biologically. In other words, they have a different biological age that reflects varied physiological traits....
Oleh Lushchak

The age-dependent impacts of treadmill exercise on cognitive impairments by reducing inflammation and oxidative stress in the hippocampus of morphine-exposed rats: the role of SIRTs 3 &4 and BDNF

1 week 5 days ago
Morphine addiction has many side effects, such as cognitive disorders. On the other hand, old age alone is one of the risk factors for cognitive decline and can increase the risk of addiction. On the other hand, the positive effects of exercise as a non-pharmacological intervention on cognitive disorders have been shown through the increase of growth factors and synaptic proteins. This study will investigate the impacts of exercise on the consequences of morphine addiction in aged rats, relying...
Saeedeh Ahmadi Nejad

Blood-based biomarkers in centenarians and non-centenarians: a matched, population-based retrospective cohort study using primary care records in Catalonia, Spain

1 week 5 days ago
The global increase in life expectancy has sparked growing interest in the factors that contribute to exceptional longevity. Between 1990 and 2015, the number of centenarians worldwide more than quadrupled. This study aimed to analyse the relationship between blood-based biomarkers and the likelihood of reaching 100 years of age in Catalonia (2015-2022), and to examine how biomarker variations during COVID-19 affected longevity. Using a retrospective cohort study based on primary care electronic...
Manuel A Moreno