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Dysfunction of the episodic memory network in the Alzheimer's disease cascade

1 day 5 hours ago
Alzheimer's disease (AD) is a major cause of dementia and cognitive decline. Here, we assessed how episodic memory (EM) network dysfunction, a hallmark of AD, is related to the longitudinal progression of AD biomarkers, neurodegeneration and cognition using data from the DZNE DELCODE study. This data set includes over 1000 longitudinal functional magnetic resonance imaging measurements of EM network function. We related activation and deactivation of EM to individual disease progression scores...
René Lattmann

Redox rhythms promote fitness by modulating ageing-dependent reprogramming

1 day 5 hours ago
Ageing leads to diurnal misalignment with a global reduction in physiological fitness, yet the mechanisms underlying such age-related diurnal reprogramming and its role in ageing remain poorly understood. Here we generate diurnal transcriptomes across eight peripheral tissues and reveal that disrupted redox oscillations are common diurnal alterations in organismal ageing. Restoring redox rhythms through the time-restricted application of antioxidants and pro-oxidants markedly improved glucose...
Xiaoman Wang

Organellar insights in ageing and longevity

1 day 5 hours ago
Metabolic processes shape ageing and longevity at multiple levels. Emerging evidence shows that many of these processes are orchestrated within and between cellular organelles. Organelles function not only as metabolic reactors but also as signalling hubs, and their coordination plays crucial roles in maintaining cellular homeostasis and promoting organismal fitness. Rather than acting in isolation, organelles engage in dynamic crosstalk through membrane contact sites, metabolite exchange and...
Philip Mannino

Interactions between rare variants in DNA repair genes and cardiometabolic risk explain more variability in cognitive function

1 day 5 hours ago
The brain is vulnerable to DNA damage and cardiometabolic risk. Yet, whether genetic variation in DNA repair interacts with cardiometabolic factors to explain cognitive variability remains unclear. Participants (n = 376,533) of white-British ancestry from the UK biobank with cognitive, neuroimaging, and whole-exome sequencing data were included. Six cognitive outcomes were assessed: fluid intelligence (FIQ), symbol-digit matching task (SDMT), visual matching (MATCH), trail making (TRAIL1 and...
Nicolas Cherbuin

Zfp462 Is a Key Mediator of Osteoblast Differentiation and Might Contribute to Age-Related Bone Loss

1 day 5 hours ago
Senile osteoporosis is characterized by a progressive decline in bone formation. Our study identifies Zfp462/ZNF462 as a novel regulator of osteoblast differentiation, providing new mechanistic insights into the aging-related change in bone formation. Here, we demonstrate that ZNF462, MOZ, and RUNX2 physically interact with each other and promote osteoblastic bone formation by increasing RUNX2 activity and histone H3 acetylation. Importantly, we reveal that aging decreases ZNF462 expression in...
Jin-Man Kim

Telomerase Knockout in Myeloid Cells Predisposes Mice to Foam Cell Formation, Dyslipidemia, Lung Fibrosis, and Cardiac Dysfunction

1 day 5 hours ago
Aging-associated changes in myeloid cells are incompletely understood. One of the culprits of aging is the downregulation of the Tert gene coding for the catalytic subunit of telomerase. Studies of mouse models with Tert knockout (KO) in specific cells have revealed the importance of the telomere-independent noncanonical function of TERT in supporting mitochondrial metabolism and protection from cell senescence. To investigate the role of TERT in myeloid cells (MCs), we analyzed mice with Tert...
Zhanguo Gao

Global scale-free brain activity as a potential neural signature of visual information processing in aging

1 day 5 hours ago
INTRODUCTION: Confluent evidence suggests that aging is associated with a reduction in the spectral slope of neural recordings. This phenomenon has been hypothesized to reflect an increase in the ratio of excitatory and inhibitory (E/I) balance. As neural E/I ratio is considered essential for cognitive functioning, this study investigated whether spectral slope (β) predicts cognitive performance in the older adults and could serve as a potential neural signature of cognitive aging. Nevertheless,...
Frigyes Samuel Racz

Stem cell control in the lung by an autocrine injury-activated Igf complex

2 days 5 hours ago
Stem cells proliferate after injury to repair damaged tissue, and chronic injury can promote cancer. However, the injury-activated signals and regulatory mechanisms, and their relationship to cancer, are poorly understood. Here, we identified insulin-like growth factor 2 (Igf2) as an injury-activated mitogen for lung neuroendocrine stem cells, which are facultative airway progenitors and a cell of origin of small-cell lung cancer in mice. Igf2 was constitutively produced by the stem cells but...
Yue Zhang

Cardiovascular imaging reveals pathways linking cardiovascular risk factors to brain aging and cognition

2 days 5 hours ago
Cardiovascular risk (CVR) factors exert effects that extend beyond the vascular system, influencing brain structure, neural function, and cognitive performance. The mechanisms by which CVR factors exert these effects remain unclear. Here, we specifically investigate the impact of CVR factors on brain aging, testing whether quantitative measures of the heart and major arteries mediate the CVR-brain-age relationship. Using longitudinal UK Biobank data, we infer individual brain age estimates based...
Yalda Amirmoezzi

Oncogenic and tumor-suppressive forces converge on a progenitor niche at the benign-to-malignant transition

2 days 5 hours ago
The benign-to-malignant transition is a defining step in cancer progression. To investigate when and how malignancy initiation occurs and tissue reorganization proceeds, we combine single-cell and spatial transcriptomic profiling in mouse models of pancreatic ductal adenocarcinoma (PDAC) that capture spontaneous p53 loss. Among Kras-mutant cells, we find that oncogenic and tumor-suppressive programs, including those controlled by p53, CDKN2A, and SMAD4, are co-activated in a discrete...
José Reyes