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The locus coeruleus (LC) is a brainstem nucleus that provides the primary source of noradrenaline (NA) in the nervous system and optimizes behavioral performance in mammals. In humans, the LC shows Alzheimer's disease (AD)-like pathology at its earliest stages, but little is known about LC integrity in normative, non-pathological aging. The present research addresses these gaps by investigating neuron numbers, densities of glia and vasculature, and volume of the LC itself in cognitively assessed...

Cell type-specific actions of disease genes add a significant layer of complexity to the genetic architecture underlying diseases, obscuring our understanding of disease mechanisms. Single-cell omics have revealed the functional roles of genes at the cellular level, identifying cell types critical for disease progression. Often, a gene impact on disease through its altered network within specific cell types, rather than mere changes in expression levels. To explore the cell type-specific roles...

We used an untargeted mass spectrometric approach, tandem mass tag proteomics, for the identification of proteomic signatures in genetic frontotemporal dementia (FTD). A total of 238 cerebrospinal fluid (CSF) samples from the Genetic FTD Initiative were analyzed, including samples from 107 presymptomatic (44 C9orf72, 38 GRN, and 25 MAPT) and 55 symptomatic (27 C9orf72, 17 GRN, and 11 MAPT) mutation carriers as well as 76 mutation-negative controls ("noncarriers"). We found shared and distinct...

Macrophages accumulate lipid droplets (LDs) under stress and inflammatory conditions. Despite the presence of LD-loaded macrophages in many tissues, including the brain, their contribution to neurodegenerative disorders remains elusive. This study investigated the role of lipid metabolism in Alzheimer's disease (AD) by assessing the contribution of LD-loaded brain macrophages, including microglia and border-associated macrophages (BAMs), in an AD mouse model. Particularly, BAMs and activated...

Circadian rhythms control the diurnal nature of many physiological, metabolic, and immune processes. We hypothesized that age-related impairments in circadian rhythms are associated with high susceptibility to bacterial respiratory tract infections. Our data show that the time-of-day difference in the control of Streptococcus pneumoniae infection is altered in elderly mice. A lung circadian transcriptome analysis revealed that aging alters the daily oscillations in the expression of a specific...

The elderly face elevated mortality risk due to rising temperature. Previous assessments of temperature-related mortality, however, lack a comprehensive analysis of distinct impacts of temperature change across different timescales and characteristics. Using a longitudinal survey of 27,233 elderly Chinese citizens from 2005 to 2018, we establish connections between rising temperatures, temperature variability, and extreme heat with increased mortality risk, assessed through four annual metrics...

Long-awaited data sets pinpoint roots of the world’s largest language family

The ovarian reserve defines female reproductive lifespan, which in humans spans decades due to the maintenance of meiotic arrest in non-growing oocytes (NGOs) residing in primordial follicles. Unknown is how the chromatin state of NGOs is established to enable long-term maintenance of the ovarian reserve. Here, we show that a chromatin remodeler, CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, establishes chromatin states required for formation and maintenance of the...

CONCLUSIONS: Higher and increasing MVPA over time is associated with better neuropsychiatric health in individuals aged ≥ 70 years. Future studies should prioritize evaluating detailed PA trajectories to better understand how different doses, intensities, and modalities of PA impact neuropsychiatric decline in older adults.

The CONSORT 2010 statement is a guideline that provides an evidence-based checklist of minimum reporting standards for randomized trials. With the rapid growth of Artificial Intelligence (AI) based interventions in the past 10 years, the CONSORT-AI extension was created in 2020 to provide guidelines for AI-based randomized controlled trials (RCT). The Clin-STAR "Around the EQUATOR" series features existing reported standards while also highlighting the inherent complexities of research involving...

Gout is a prevalent form of inflammatory arthritis that occurs due to high levels of uric acid in the blood leading to the formation of urate crystals in and around the joints, particularly affecting the elderly. Recent research has provided evidence of distinct differences in the gut microbiota of patients with gout and hyperuricemia compared to healthy individuals. However, the link between gut microbiota and age-related gout remained underexplored. Our study found that gut microbiota plays a...

Epigenetic clocks use DNA methylation (DNAm) levels to predict an individual's biological age. However, relationships between lifestyle/biomarkers and epigenetic age acceleration (EAA) in Asian populations remain unknown. We here explored associations between lifestyle factors, physiological conditions, and epigenetic markers, including HannumEAA, IEAA, PhenoEAA, GrimEAA, DunedinPACE, DNAm-based smoking pack-years (DNAmPACKYRS), and DNAm plasminogen activator inhibitor 1 level (DNAmPAI1). A...

p16INK4a is a crucial tumor suppressor and regulator of cellular senescence, forming a molecular bridge between aging and cancer. Dysregulated p16INK4a expression is linked to both premature aging and cancer progression, where non-coding RNAs (ncRNAs) such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs) play key roles in modulating its function. These ncRNAs interact with p16INK4a through complex post-transcriptional and epigenetic mechanisms,...

This study investigates the impact and mechanisms of Rasayana Churna, an Ayurvedic poly-herbal formulation, in treating aging-related disorders through text mining, network pharmacology, molecular docking simulation, Super-MMPBSA, and density functional theory. The text mining of Rasayana Churna highlighted the diverse therapeutic potential of Phyllanthus emblica, Tinospora cordifolia, and Tribulus terrestris in managing aging-related disorders through their antidiabetic, antioxidant, and...

Aging is a multifactorial process that significantly impairs organismal function. Yeast is one of the model organisms used in aging research. Our understanding of the impact of the cell wall on aging remains elusive. Yeast cell wall is a complex and dynamic structure that plays a crucial role in the growth, survival, and aging of Saccharomyces cerevisiae. In this study, we demonstrated for the first time that the deletion of genes involved in cell wall biogenesis leads to significant impact on...

Neuroinflammation is closely linked to aging, which damages the structure and function of the brain. It is caused by the intricate interactions of immune cells in the aged brain, such as the dysregulated glial cells and the dysfunctional astrocytes. Aging-associated chronic low inflammation, referred to as neuroinflammaging, shows an upregulated proinflammatory response. Autophagy and senescence play crucial roles as moderators of aging and neuroinflammatory responses. The dysregulated...

Alzheimer disease (AD) is a progressive neurodegenerative disease with a strong genetic component. Although autosomal dominant mutations and common risk variants in AD risk have been extensively studied, the genetic underpinning of polygenic AD remains incompletely understood. Rare variants could elucidate part of the missing heritability in AD. Rare variant research gained momentum with the discovery of a rare variant in TREM2, along with loss-of-function variants in ABCA7 and SORL1, and has...

Aging is associated with intestinal dysbiosis, a condition characterized by diminished microbial biodiversity and inflammation. This leads to increased vulnerability to extraintestinal manifestations such as autoimmune, metabolic, and neurodegenerative conditions thereby accelerating mortality. As such, modulation of the gut microbiome is a promising way to extend healthspan. In this study, we explore the effects of fecal microbiota transplant (FMT) from long-living Ames dwarf donors to their...

We assessed the association of serum metabolites with the occurrence of major adverse cardiovascular events (MACE) in middle-aged and elderly individuals, explored the value of metabolomics in predicting MACE, and compared the distinctions in MACE risk-related metabolic biomarkers between middle-aged and elderly groups. Among the participants of the UK Biobank who underwent baseline assessment through nuclear magnetic resonance (NMR)-based metabolomic profiling of 168 serum metabolites and had...

UDP-GlcNAc serves as a building block for glycosaminoglycan (GAG) chains in cartilage proteoglycans and simultaneously acts as a substrate for O-GlcNAcylation. Here, we show that transporters for UDP-GlcNAc to the endoplasmic reticulum (ER) and Golgi are significantly downregulated in osteoarthritic cartilage, leading to increased cytosolic UDP-GlcNAc and O-GlcNAcylation in chondrocytes. Mechanistically, upregulated O-GlcNAcylation governs the senescence-associated secretory phenotype (SASP) by...