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Disease-modifying therapies for Alzheimer's disease: Clinical trial progress and opportunity

1 month ago
The U.S. Food and Drug Administration (FDA) recently approved lecanemab and donanemab for the treatment of early symptomatic Alzheimer's disease (AD) after their phase III trials reached endpoints. These two anti-amyloid β monoclonal antibodies represent the latest promise of disease-modifying therapy (DMT) for AD, which undoubtedly reignites new hope for DMTs to combat the staggering financial and human costs of AD. However, in addition to these two successful antibodies, there have been...
Yujie Zhang

Enhancing mitochondrial one-carbon metabolism is neuroprotective in Alzheimer's disease models

1 month ago
Alzheimer's disease (AD) is the most common form of age-related dementia. In AD, the death of neurons in the central nervous system is associated with the accumulation of toxic amyloid β peptide (Aβ) and mitochondrial dysfunction. Mitochondria are signal transducers of metabolic and biochemical information, and their impairment can compromise cellular function. Mitochondria compartmentalise several pathways, including folate-dependent one-carbon (1C) metabolism and electron transport by...
Yizhou Yu

Ten Americas: a systematic analysis of life expectancy disparities in the USA

1 month ago
BACKGROUND: Nearly two decades ago, the Eight Americas study offered a novel lens for examining health inequities in the USA by partitioning the US population into eight groups based on geography, race, urbanicity, income per capita, and homicide rate. That study found gaps of 12·8 years for females and 15·4 years for males in life expectancy in 2001 across these eight groups. In this study, we aimed to update and expand the original Eight Americas study, examining trends in life expectancy from...
Laura Dwyer-Lindgren

Systematic review of what people know about brain health

1 month ago
OBJECTIVES: As we age our cognitive abilities can change. However, the degree of change experienced is influenced by a range of factors. To understand what the public know about risk and protective factors for cognitive ageing, a systematic review was conducted of studies considering what people know about brain health.
Malwina A Niechcial

Single-cell transcriptomics unveils molecular signatures of neuronal vulnerability in a mouse model of prion disease that overlap with Alzheimer's disease

1 month ago
Understanding why certain neurons are more sensitive to dysfunction and death caused by misfolded proteins could provide therapeutically relevant insights into neurodegenerative disorders. Here, we harnessed single-cell transcriptomics to examine live neurons isolated from prion-infected female mice, aiming to identify and characterize prion-vulnerable neuronal subsets. Our analysis revealed distinct transcriptional responses across neuronal subsets, with a consistent pathway-level depletion of...
Jessy A Slota

lncRNAs maintain the functional phase state of nucleolar prion-like protein to facilitate rRNA processing

1 month ago
Liquid-to-solid phase transition of proteins with prion-like domains (PLDs) has been associated with neurodegenerative diseases and aging. High protein concentration is one important aspect triggering the transition; however, several prion-like proteins, including fibrillarin (FBL), an important phase-separated protein in the nucleolus for pre-rRNA processing, show relatively high expression levels in certain cells, especially cancer cells, without obvious phase transitions and growth arrest....
Yu-Meng Sun

Aging modulates the impact of cognitive interference subtypes on dynamic connectivity across a distributed motor network

1 month ago
Research has shown age-related declines in cognitive control in the context of interference, but these studies have focused on frontoparietal networks and less is known about impacts on motor response-related dynamics in the face of distractors. Thus, we examined whether healthy aging affected connectivity between attention networks and motor circuitry using a multisource interference task and magnetoencephalography in 72 healthy-aging participants (28-63 years-old). Our results indicated...
Jake J Son

Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's disease

1 month ago
The pathogenesis of Alzheimer's disease (AD) depends on environmental and heritable factors, with its molecular etiology still unclear. Here we present a spatial transcriptomic (ST) and single-nucleus transcriptomic survey of late-onset sporadic AD and AD in Down syndrome (DSAD). Studying DSAD provides an opportunity to enhance our understanding of the AD transcriptome, potentially bridging the gap between genetic mouse models and sporadic AD. We identified transcriptomic changes that may...
Emily Miyoshi

The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging

1 month ago
In the era of synthetic biology, design, construction, and utilization of synthetic chromosomes with unique features provide a strategy to study complex cellular processes such as aging. Herein, we successfully construct the 884 Kb synXIII of Saccharomyces cerevisiae to investigate replicative aging using these synthetic strains. We verify that up-regulation of a rRNA-related transcriptional factor, RRN9, positively influence replicative lifespan. Using SCRaMbLE system that enables inducible...
Chun Zhou

Emerging insights in senescence: pathways from preclinical models to therapeutic innovations

1 month ago
Senescence is a crucial hallmark of ageing and a significant contributor to the pathology of age-related disorders. As committee members of the young International Cell Senescence Association (yICSA), we aim to synthesise recent advancements in the identification, characterisation, and therapeutic targeting of senescence for clinical translation. We explore novel molecular techniques that have enhanced our understanding of senescent cell heterogeneity and their roles in tissue regeneration and...
Luke Mansfield

Transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states

1 month ago
In aging, skeletal muscle regeneration declines due to alterations in both myogenic and non-myogenic cells and their interactions. This regenerative dysfunction is not understood comprehensively or with high spatiotemporal resolution. We collected an integrated atlas of 273,923 single-cell transcriptomes and high-resolution spatial transcriptomic maps from muscles of young, old and geriatric mice (~5, 20 and 26 months old) at multiple time points following myotoxin injury. We identified eight...
Lauren D Walter

Molecular and genetic insights into human ovarian aging from single-nuclei multi-omics analyses

1 month ago
The ovary is the first organ to age in the human body, affecting both fertility and overall health. However, the biological mechanisms underlying human ovarian aging remain poorly understood. Here we present a comprehensive single-nuclei multi-omics atlas of four young (ages 23-29 years) and four reproductively aged (ages 49-54 years) human ovaries. Our analyses reveal coordinated changes in transcriptomes and chromatin accessibilities across cell types in the ovary during aging, notably mTOR...
Chen Jin

Plasminogen Activator Inhibitor-1 in the Pathophysiology of Late Life Depression

1 month ago
INTRODUCTION: Late life depression (LLD) is characterized by specific clinical features including a high frequency of vascular form and frequent antidepressant treatment resistance. The expression and functions of the serine protease inhibitor, Plasminogen Activator Inhibitor-1 (PAI-1) is known to be altered by aging, vascular damage, insulin levels associated with a sedentary lifestyle, chronic stress leading to hypercortisolemia, and inflammatory changes linked to stress responses. These...
L Métivier

Unknown roles of tau pathology in neurological disorders. Challenges and new perspectives

1 month ago
Aging presents progressive changes that increase the susceptibility of the central nervous system (CNS) to suffer neurological disorders (NDs). Several studies have reported that an aged brain suffering from NDs shows the presence of pathological forms of tau protein, a microtubule accessory protein (MAP) critical for neuronal function. In this context, accumulative evidence has shown a pivotal contribution of pathological forms of tau to Alzheimer's disease (AD) and tauopathies. However,...
Margrethe A Olesen

Effects of age and dietary methionine restriction on cognitive and behavioural phenotypes in the rTg4510 mouse model of frontotemporal dementia

1 month ago
Metabolic disorders such as diabetes and obesity are linked to neurodegenerative diseases, with evidence of lower brain glucose metabolism and insulin resistance in dementia patients. Dietary methionine restriction (MR) is a nutritional intervention that enhances insulin sensitivity and delays ageing-associated metabolic alterations, however, its impact on neurodegenerative diseases is not fully understood. Here, we examined the behavioural and metabolic phenotypes of a murine tauopathy model...
Marina Souza Matos

Dual impacts of serine/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation

1 month ago
The effect of the serine/glycine-free diet (-SG diet) on colorectal cancer (CRC) remains unclear; meanwhile, programmed death-1 (PD-1) inhibitors are less effective for most CRC patients. Here, we demonstrate that the -SG diet inhibits CRC growth and promotes the accumulation of cytotoxic T cells to enhance antitumor immunity. Additionally, we also identified the lactylation of programmed death-ligand 1 (PD-L1) in tumor cells as a mechanism of immune evasion during cytotoxic T cell-mediated...
Huan Tong

Unknown roles of tau pathology in neurological disorders. Challenges and new perspectives

1 month ago
Aging presents progressive changes that increase the susceptibility of the central nervous system (CNS) to suffer neurological disorders (NDs). Several studies have reported that an aged brain suffering from NDs shows the presence of pathological forms of tau protein, a microtubule accessory protein (MAP) critical for neuronal function. In this context, accumulative evidence has shown a pivotal contribution of pathological forms of tau to Alzheimer's disease (AD) and tauopathies. However,...
Margrethe A Olesen