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Senescent microglia with shortened telomeres secrete soluble DLK1 to induce aging-associated hypomyelination and neuronal dysfunction

1 day 3 hours ago
Aging is the major risk factor for neurodegenerative disease, yet the mechanisms linking physiological aging to brain dysfunction remain unclear. We investigated the brains of telomere-shortened mice and observed lipofuscinosis, hypomyelination, microglial atrophy, and cognitive deficits. Single-nucleus RNA sequencing (snRNA-seq) revealed accelerated glial aging and elevated microglial senescence pathways. In a senescence model of human induced pluripotent stem cell (iPSC)-derived microglia,...
Bangyan Liu

Clonal hematopoiesis of undetermined potential as an emerging determinant of inflammageing, and age-related diseases: potential role as biomarker and target

1 day 3 hours ago
Clonal hematopoiesis of undetermined potential (CHIP), initially discovered as a mere hematological curiosity, now represents a clinically significant factor that is changing our view of ageing, inflammaging and the risk of age-related diseases (ARDs). In line with this, new meta-analyses link the presence of CHIP to higher all-cause mortality from ARDs and to an increase in adverse events in the presence of larger clones. Mechanistically, CHIP induces inflammaging, but a bidirectional...
Chiara Motisi

Plant-derived extracellular vesicles (PDEVs) in anti-aging research: A review of biomedical characteristics and therapeutic applications

1 day 3 hours ago
Aging is a complex, irreversible physiological process characterized by gradual deterioration of tissue structure and function, accompanied by impaired regenerative capacity, dysregulated immune homeostasis, and increased susceptibility to chronic age-related diseases (e.g., neurodegenerative disorders, metabolic syndromes, age-related skin lesions, and inflammatory bowel disease). In recent years, plant-derived extracellular vesicles (PDEVs), the lipid bilayer membrane vesicles released by...
Xiaolin Huang

Beyond senescence entry: individual-cell fates, population outcomes and therapeutic implications in ageing and disease

1 day 3 hours ago
Cellular senescence is a stress-response program characterized by durable proliferative arrest, but senescence entry does not determine a single biological outcome. Confusion between the fate of an individual cell and the behavior of a senescent-cell population has obscured interpretation across development, ageing and disease. This Review develops a fate-resolved framework that distinguishes continued arrest, cell death, physical shedding and, under restricted conditions, sustained...
Guosong Wang

Integrating experimental evolution and transcriptomics reveals the phenotypic and molecular architecture of the pace-of-life syndrome

1 day 3 hours ago
Phenotypic traits often covary through shared genetic and environmental influences, shaping the evolution of integrated life-history strategies. In particular, correlations between behavioral and life-history traits form the core of the pace-of-life syndrome (POLS) hypothesis, yet direct experimental tests of its evolutionary and molecular foundations remain limited. Here, we combined experimental evolution and transcriptomic analyses to investigate the phenotypic and molecular architecture of...
Kentarou Matsumura

Beyond the scaffold: Glia as architects of the neural extracellular matrix

1 day 3 hours ago
Astrocytes, oligodendrocyte lineage cells, and microglia dynamically shape the neural extracellular matrix (ECM) across brain development and aging. Recent findings highlight the potential of glial regulation of the ECM as a framework for understanding circuit formation and identify previously unrecognized targets in neurological diseases.
John Lenon de Souza Santos

Human PMS1-dependent non-canonical mismatch repair engages with MBD4 to repair methylated CpG deamination

1 day 3 hours ago
CpG dinucleotides are mutational hotspots due to spontaneous deamination of 5-methylcytosine (5mC), resulting in T:G mismatches that can lead to CpG>TpG transitions. These mutations are a hallmark of aging and cancer and play a central role in the evolution of vertebrate genomes. We have previously uncovered MBD4 as the primary base excision repair (BER) glycosylase responsible for 5mC deamination repair. Here, we employ an APOBEC1 deaminase fused to a catalytically dead Cas9 to induce targeted...
Anaïs Le Ven

Inhibiting Ribosomal RNA Synthesis in C. elegans Protects Against Reductive Stress During de novo Fatty Acid Synthesis Deficiency

1 day 3 hours ago
Reductive stress has remained underappreciated as a significant disrupter of redox homeostasis. Recent studies have begun to link the accumulation of NADH and NADPH to the development and progression of metabolic diseases such as cancer, cardiac disease, and diabetes. In this study we use the nematode Caenorhabditis elegans to examine the phenomenon of catastrophic reductive-death caused by combined biguanide treatment and fasn-1 deficiency. This process of synergistic biguanide-induced...
Jen F Rotti

In vivo mapping of striatal neurodegeneration in Huntington's disease with Soma and Neurite Density Imaging

1 day 3 hours ago
Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by progressive cognitive and motor decline driven by basal ganglia (BG) atrophy. Clinical trials of novel disease-modifying therapies are ongoing, creating a need for sensitive non-invasive imaging biomarkers. Soma and Neurite Density Imaging (SANDI) is a multi-shell diffusion MRI model that estimates intracellular signal fractions from sphere-shaped soma and shows promise as a marker of neurodegeneration. The...
Vasileios Ioakeimidis

Amenable Mortality Among Older Brazilians: Evidence From the Brazilian Longitudinal Study of Aging (ELSI-Brazil)

1 day 3 hours ago
BackgroundAmenable mortality, deaths preventable through timely and effective healthcare, is a widely used indicator of health system performance, yet evidence is lacking on its individual-level determinants in Brazil.MethodsWe used data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), a representative cohort of adults aged 50 and older. Deaths were classified as amenable using both the Brazilian and the Pan American Health Organization's definitions. Semi-parametric competing risks...
James Macinko