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Ergothioneine improves healthspan of aged animals by enhancing cGPDH activity through CSE-dependent persulfidation

4 months 2 weeks ago
Ergothioneine (ET), a dietary thione/thiol, is receiving growing attention for its possible benefits in healthy aging and metabolic resilience. Our study investigates ET's effects on healthspan in aged animals, revealing lifespan extension and enhanced mobility in Caenorhabditis elegans, accompanied by improved stress resistance and reduced age-associated biomarkers. In aged rats, ET administration enhances exercise endurance, muscle mass, and vascularization, concomitant with higher NAD^(+)...
Dunja Petrovic

Depressive intensity, duration, and their associations with cognitive decline: a population-based study in Korea

4 months 2 weeks ago
Existing epidemiological studies have ignored the effect of depressive duration on cognitive decline despite the presence of biological cues and understudied the depression-cognition association in Asian countries in the context of increasing cognitive burden worldwide. We aimed to comprehensively characterize the effects of depressive duration and intensity on cognitive decline at the population level. A total of 6406 individuals from the Korean Longitudinal Study of Aging (KLoSA) from 2010 to...
Kai Lu

Immune evasion through mitochondrial transfer in the tumour microenvironment

4 months 2 weeks ago
Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack¹. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses^(2-4). However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells....
Hideki Ikeda

Multiscale footprints reveal the organization of cis-regulatory elements

4 months 2 weeks ago
Cis-regulatory elements (CREs) control gene expression and are dynamic in their structure and function, reflecting changes in the composition of diverse effector proteins over time¹. However, methods for measuring the organization of effector proteins at CREs across the genome are limited, hampering efforts to connect CRE structure to their function in cell fate and disease. Here we developed PRINT, a computational method that identifies footprints of DNA-protein interactions from bulk and...
Yan Hu

The maternal X chromosome affects cognition and brain ageing in female mice

4 months 2 weeks ago
Female mammalian cells have two X chromosomes, one of maternal origin and one of paternal origin. During development, one X chromosome randomly becomes inactivated^(1-4). This renders either the maternal X (X(m)) chromosome or the paternal X (X(p)) chromosome inactive, causing X mosaicism that varies between female individuals, with some showing considerable or complete skew of the X chromosome that remains active^(5-7). Parent-of-X origin can modify epigenetics through DNA methylation^(8,9) and...
Samira Abdulai-Saiku

Amyloid-associated hyperconnectivity drives tau spread across connected brain regions in Alzheimer's disease

4 months 2 weeks ago
In Alzheimer's disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperactivity and hyperconnectivity, and preclinical research has shown that tau spreads across connected neurons in an activity-dependent manner. Here, we...
Sebastian N Roemer-Cassiano

Functional classification of tauopathy strains reveals the role of protofilament core residues

4 months 2 weeks ago
Distinct tau amyloid assemblies underlie diverse tauopathies but defy rapid classification. Cell and animal experiments indicate tau functions as a prion, as different strains propagated in cells cause unique, transmissible neuropathology after inoculation. Strain amplification requires compatibility of the monomer and amyloid template. We used cryo-electron microscopy to study one cell-based yellow fluorescent protein (YFP)-tagged strain, resolving its amyloid nature. We then used sequential...
Jaime Vaquer-Alicea