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The canonical RPA complex interacts with Est3 to regulate yeast telomerase activity
In most eukaryotic organisms, cells that rely on continuous cell division employ the enzyme telomerase which replenishes chromosome termini through the addition of telomeric repeats. In budding yeast, the telomerase holoenzyme is composed of a catalytic core associated with two regulatory subunits, Est1 and Est3. The Est1 protein binds a telomere-specific RPA-like complex to recruit telomerase to chromosome ends. However, the regulatory function of the Est3 subunit has remained elusive. We...
Development and validation of a sensitive sandwich ELISA against human PINK1
The ubiquitin kinase and ligase PINK1 and PRKN together label damaged mitochondria for their elimination in lysosomes by selective autophagy (mitophagy). This cytoprotective quality control pathway is genetically linked to familial Parkinson disease but is also altered during aging and in other neurodegenerative disorders. However, the molecular mechanisms of these mitophagy changes remain uncertain. In healthy mitochondria, PINK1 protein is continuously imported, cleaved, and degraded, but...
Development and validation of a sensitive sandwich ELISA against human PINK1
The ubiquitin kinase and ligase PINK1 and PRKN together label damaged mitochondria for their elimination in lysosomes by selective autophagy (mitophagy). This cytoprotective quality control pathway is genetically linked to familial Parkinson disease but is also altered during aging and in other neurodegenerative disorders. However, the molecular mechanisms of these mitophagy changes remain uncertain. In healthy mitochondria, PINK1 protein is continuously imported, cleaved, and degraded, but...
Aging-Associated Liver Sinusoidal Endothelial Cells Dysfunction Aggravates the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease
Aging increases the susceptibility to metabolic dysfunction-associated steatotic liver disease (MASLD). Liver sinusoidal endothelial cells (LSECs) help in maintaining hepatic homeostasis, but the contribution of age-associated LSECs dysfunction to MASLD is not clear. The aim of this study was to investigate the effect of aging-associated LSECs dysfunction on MASLD. Free fatty acid-treated AML12 cells were co-cultured with young and etoposide-induced senescent TSEC cells to evaluate the...
In vivo medical imaging for assessing geroprotective interventions in humans
There is a growing interest in developing drugs with a general geroprotective effect, aimed at slowing down aging. Several compounds have been shown to increase the lifespan and reduce the incidence of age-related diseases in model organisms. Translating these results is challenging, due to the long lifespan of humans. To address this, we propose using a battery of medical imaging protocols that allow for assessments of age-related processes known to precede disease onset. These protocols, based...
How to make the perfect boiled egg—if you have the patience
New method cracks the code for a soft yolk and a cooked white
Novel TORC1 inhibitor Ecl1 is regulated by phosphorylation in fission yeast
Extender of chronological lifespan 1 (Ecl1) inhibits target of rapamycin complex 1 (TORC1) and is necessary for appropriate cellular responses to various stressors, such as starvation, in fission yeast. However, little is known about the effect of posttranslational modifications on Ecl1 regulation. Thus, we investigated the phosphorylation levels of Ecl1 extracted from yeast under conditions of sulfur or metal starvation. Mass spectrometry analysis revealed that Ecl1 was phosphorylated at Thr7,...
In a cave in Poland, signs of prehistoric cannibalism
Practice may reflect violent competition for new territory 18,000 years ago