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Age-dependent H3K9 trimethylation by dSetdb1 impairs mitochondrial UPR leading to degeneration of olfactory neurons and loss of olfactory function in <em>Drosophila</em>

11 hours 18 minutes ago
Aging is characterized by a decline in essential sensory functions, including olfaction, which is crucial for environmental interaction and survival. This decline is often paralleled by the cellular accumulation of dysfunctional mitochondria, particularly detrimental in post-mitotic cells such as neurons. Mitochondrial stress triggers the mitochondrial unfolded protein response (UPR^(MT)), a pathway that activates mitochondrial chaperones and antioxidant enzymes. Critical to the efficacy of the...
Francisco Muñoz-Carvajal

Complement receptor 3 (CR3)-dependent microglial synapse elimination drives Parkinson's disease pathogenesis in systemic inflammation

11 hours 18 minutes ago
Although systemic inflammation has been implicated in PD pathogenesis, the underlying mechanisms remain poorly understood. In this study, we investigate the pathological events in a systemic inflammation-induced PD mouse model. We demonstrate that synaptic loss in the midbrain occurs as early as 1 day after the final lipopolysaccharide (LPS) administration, preceding dopaminergic (DA) neuron degeneration, which was observed only at later stages (14 days). Early microglial activation in the...
Lei Cai

Differential Gene Expression in Human Hippocampus With Aging

11 hours 18 minutes ago
Brain aging consists of a progressive loss of functional capacities, which is associated with a progressive cognitive decline and can lead to neurodegenerative diseases. Studies comparing the underlying molecular mechanisms of the human hippocampus between young and older adults remain scarce. In our study, we completed a transcriptomic analysis from hippocampal samples of different ages and performed 2 complementary analyses. A comparison between young and old groups revealed a set of genes...
Ander Saenz-Antoñanzas

cGAS-STING/HMGB1-mediated senescence induced by LRRK2 accelerates cartilage degeneration in osteoarthritis

11 hours 18 minutes ago
Mitochondrial dysfunction-driven senescence is a central mechanism in the development of osteoarthritis (OA). Leucine-rich repeat kinase 2 (LRRK2), a multifunctional kinase implicated in maintaining mitochondrial homeostasis, has been examined in several inflammatory conditions. However, its role in regulating cellular senescence and its pathogenic contribution to OA remain insufficiently understood. To clarify the mechanism by which LRRK2 contributes to OA, RNA-seq and bioinformatics analysis...
Yantao Zhang

Protein intake and its interaction with dietary patterns on clinical outcomes among older adults

11 hours 18 minutes ago
Adequate protein intake is increasingly recognized as a key determinant of healthy aging, yet its independent and diet-dependent effects on functional decline and mortality remain uncertain. Using data from 532 adults aged ≥65 years in the English Longitudinal Study of Ageing, we examined cross-sectional and longitudinal associations between multiple protein-related parameters and clinical outcomes over six years. We also evaluated whether protein intake modified or mediated the effects of two...
Hélio José Coelho-Júnior

Human microphysiological systems of aging recreate the in vivo process expediting evaluation of anti-geronic strategies

11 hours 18 minutes ago
The search for biological mechanisms of human aging is stalled by a lack of suitable models, and it remains unknown whether and to what degree rejuvenation reported in rodents translates to people. Here we report a human induced pluripotent stem cell-derived microphysiological system modelling the white adipose tissue-liver axis in the presence of heterochronic human serum to study aging and rejuvenation in humans. We reveal changes in functional and molecular hallmarks of aging and...
Lin Qi

Functional hierarchy of the human neocortex across the lifespan

11 hours 18 minutes ago
Large-scale gradients of functional connectivity between brain areas organize the human neocortex, linking brain topography to the texture of cognition^(1,2). In adults, three dominant axes-sensory-association, visual-somatosensory and modulation-representation-run, respectively, from primary sensory to transmodal association areas, from visual to body-centred systems and from control and attention networks to default mode and sensory areas^(1-4). These gradients provide a compact description of...
Hoyt Patrick Taylor

Holotomography-based, label-free quantification of cellular dry mass as a biophysical indicator of microglial Abeta phagocytosis during senescence

11 hours 18 minutes ago
Senescent microglia undergo significant molecular and biochemical changes associated with impaired phagocytosis of amyloid-β (Aβ), a process implicated in neurodegenerative disease progression. However, quantitative biophysical metrics capable of capturing this functional impairment-and thus elucidating the role of microglial dysfunction in disease progression-remain limited. In this study, we identify cellular dry mass, measured by label-free holotomography, in combination with cell and nuclear...
Sunjeet Saha

Differential Gene Expression in Human Hippocampus With Aging

11 hours 18 minutes ago
Brain aging consists of a progressive loss of functional capacities, which is associated with a progressive cognitive decline and can lead to neurodegenerative diseases. Studies comparing the underlying molecular mechanisms of the human hippocampus between young and older adults remain scarce. In our study, we completed a transcriptomic analysis from hippocampal samples of different ages and performed 2 complementary analyses. A comparison between young and old groups revealed a set of genes...
Ander Saenz-Antoñanzas

Machine learning analysis of population-wide plasma proteins identifies hormonal biomarkers of Parkinson's disease

11 hours 18 minutes ago
With the number of Parkinson's patients expected to rise due to an aging population, there is an increasing need to identify new diagnostic markers. These markers should be affordable and suitable for routine use to monitor the population, help stratify patients for treatment pathways, and provide new avenues for therapy. Genetic predisposition and familial forms account for approximately 10% of Parkinson's disease (PD) cases, leaving a large fraction of the population with minimal effective...
Fayzan Chaudhry