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Adipose-Specific GHR Deletion Attenuates Brain Aging and Cognitive Decline in Aged Mice
Brain aging is marked by neuronal loss, synaptic deterioration, neuroinflammation, and proteinopathies, all of which contribute to cognitive decline. Although systemic suppression of growth hormone (GH)/insulin-like growth factor-1 (IGF-1) signaling has been shown to extend lifespan and enhance cognitive function, the specific role of GH signaling in adipose tissue during brain aging remains unclear. In this study, we used aged (18-24 months) adipose-specific GH receptor knockout (Ad-GHRKO) mice...
Host Oxidative Response Capacity Determines Longevity Outcomes of Microbial Interventions
Microbial communities profoundly influence host aging, yet how natural genetic variation determines microbiota-driven longevity remains unclear. By screening root-derived bacterial isolates across genetically diverse Caenorhabditis elegans strains, we identified striking phenotypic heterogeneity, ranging from lifespan extension to accelerated aging. Combining classical genetic analysis, quantitative trait locus (QTL) mapping and CRISPR-Cas9 allelic recapitulation, we identify skn-1 (Nrf2) and...
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Photoacoustic computed tomography monitors cerebrospinal fluid dynamics and glymphatic function
Cerebrospinal fluid (CSF) continuously circulates through the brain and surrounding tissues to remove metabolic waste, a process that becomes less efficient with ageing and in neurodegenerative disease. Visualizing this drainage in living animals has been difficult because existing imaging tools either lack depth, require radioactive tracers, or are too slow to capture dynamic flow. Here, we show that whole-body photoacoustic computed tomography (PACT) enables three-dimensional, real-time...
Glucosylceramide-induced ectosomes propagate pathogenic alpha-synuclein in Parkinson's disease
The intercellular transmission of α-synuclein contributes to Parkinson's disease pathology. Yet, the mechanisms of α-synuclein spread are not fully understood. Here we used live-cell microscopy to examine the impact of Parkinson's disease associated lipid alterations on α-synuclein release. We discovered that increased glucosylceramides as a consequence of reduced β-glucocerebrosidase activity induce ectosome shedding from primary neurons and from dopaminergic neurons derived from induced...
Hypertension is associated with knee osteoarthritis pain in an age-dependent manner
CONCLUSIONS: Hypertension was associated with an age-dependent decline in reported knee pain, poorer physical function, and more severe radiographic knee OA in females. These findings suggest hypertensive individuals may deviate from a progressive OA pain trajectory and contribute to discordance between joint damage and pain.