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The mitochondrial and cytoplasmic superoxide anion imbalance trigger the expression of certain cellular aging markers in HaCaT keratinocytes

6 months 1 week ago
In cells, the term "cellular aging" represents a collection of biological changes that can precede the proliferative senescence states. Cells more resistant to proliferative senescence, such as the ones found in the basal layer of the epidermis, may also exhibit these aging patterns. Therefore, cellular aging events could be induced by endogenous signals named here as cellular aging triggers (CATs) components. The superoxide anion (O(2)⁻) could be a prime candidate for a CATs, as it is...
Nathalia Cardoso de Afonso Bonotto

Chronic kidney disease and aging: dissecting the p53/p21 pathway as a therapeutic target

6 months 1 week ago
Chronic kidney diseases (CKD) are a group of multi-factorial disorders that markedly impair kidney functions with progressive renal deterioration. Aging contributes to age-specific phenotypes in kidneys, which undergo several structural and functional alterations, such as a decline in regenerative capacity and increased fibrosis, inflammation, and tubular atrophy, all predisposing them to disease and increasing their susceptibility to injury while impeding their recovery. A central feature of...
Kavita Goyal

Centenarians-the way to healthy vascular ageing and longevity: a review from VascAgeNet

6 months 1 week ago
The prevalence of centenarians, people who lived 100 years and longer, is steadily growing in the last decades. This exceptional longevity is based on multifaceted processes influenced by a combination of intrinsic and extrinsic factors such as sex, (epi-)genetic factors, gut microbiota, cellular metabolism, exposure to oxidative stress, immune status, cardiovascular risk factors, environmental factors, and lifestyle behavior. Epidemiologically, the incidence rate of cardiovascular diseases is...
Sabrina Summer

Impact of dementia and mild cognitive impairment on bone health in older people

6 months 1 week ago
Mild cognitive impairment, dementia and osteoporosis are common diseases of ageing and, with the increasingly ageing global population, are increasing in prevalence. These conditions are closely associated, with shared risk factors, common underlying biological mechanisms and potential direct causal pathways. In this review, the epidemiological and mechanistic links between mild cognitive impairment, dementia and skeletal health are explored. Discussion will focus on how changes in brain and...
Elizabeth M Curtis

The glial UDP-glycosyltransferase Ugt35b regulates longevity by maintaining lipid homeostasis in Drosophila

6 months 1 week ago
Lipid droplets (LDs) are dynamic organelles essential for lipid storage and organismal survival. Studies have highlighted the importance of glial function in brain LD formation during aging; however, the genes and mechanisms involved remain elusive. Here, we found that Ugt35b, a member of the uridine diphosphate (UDP)-glycosyltransferases that catalyze the transfer of glycosyl groups to acceptors, is highly expressed in glia and crucial for Drosophila lifespan. By integrating multiomics data, we...
Lihong Sheng

Proteome profiling of cerebrospinal fluid using machine learning shows a unique protein signature associated with APOE4 genotype

6 months 1 week ago
Proteome changes associated with APOE4 variant carriage that are independent of Alzheimer's disease (AD) pathology and diagnosis are unknown. This study investigated APOE4 proteome changes in people with AD, mild cognitive impairment, and no impairment. Clinical, APOE genotype, and cerebrospinal fluid (CSF) proteome and AD biomarker data was sourced from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Proteome profiling was done using supervised machine learning. We found an...
Artur Shvetcov

DNMT3a Deficiency Contributes to Anesthesia/Surgery-Induced Synaptic Dysfunction and Cognitive Impairment in Aged Mice

6 months 1 week ago
Perioperative neurocognitive disorder (PND) is a severe postoperative complication in older patients. Epigenetic changes are hallmarks of senescence and are closely associated with cognitive impairment. However, the effects of anesthesia and surgery on the aging brain's epigenetic regulatory mechanisms and its impact on cognitive impairment remain unclear. Using a laparotomy PND model, we report significant reduction in DNA methyltransferase 3a (DNMT3a) in hippocampal neurons of aged mice, which...
Peilin Cong

Evidence of compensatory neural hyperactivity in a subgroup of breast cancer survivors treated with chemotherapy and its association with brain aging

6 months 1 week ago
INTRODUCTION: Chemotherapy-related cognitive impairment (CRCI) remains poorly understood in terms of the mechanisms of cognitive decline. Neural hyperactivity has been reported on average in cancer survivors, but it is unclear which patients demonstrate this neurophenotype, limiting precision medicine in this population.
Michele M Mulholland

A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion

6 months 1 week ago
The brain's primary immune cells, microglia, are a leading causal cell type in Alzheimer's disease (AD). Yet, the mechanisms by which microglia can drive neurodegeneration remain unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a microglia subset with neurodegenerative outcomes. Autonomous activation of ISR in microglia is sufficient to induce early features of the ultrastructurally distinct "dark microglia" linked to...
Anna Flury