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Relationship of Visual Impairment and Poor Mobility With Mortality
CONCLUSIONS: Older adults with both VI and poor mobility are at an additive increased risk of mortality. Future interventions may want to target older adults with both VI and poor mobility to improve survival.
Replication stress responses in human lymphocytes change sex-specifically during aging
The varying incidence of aging-related diseases and the gender gap in life expectancy suggest differences in the aging process between the sexes. Yet, little is known about sex-specific differences in genomic instability, a key factor in aging. Here, we analyzed DNA damage responses (DDRs) in cycling peripheral blood lymphocytes (PBL) and hematopoietic stem and progenitor cells (HSPC) from female and male donors of different age, focusing on replication stress. Transcriptomics revealed striking...
Senescence Cell Induction Methods Display Diverse Metabolic Reprogramming and Reveal an Underpinning Serine/Taurine Reductive Metabolic Phenotype
The relationship between in vitro senescence cell induction and intracellular biomolecular dysregulation is still poorly understood. In this study, we have found that a range of metabolic subphenotypes exists and is dependent on the induction method that is used. To develop understanding of these subphenotypes, we developed and employed a novel bioanalytical pipeline integrating untargeted metabolomics, label-free proteomics, and stable isotope tracing alongside cellular deformability...
Tumor-promoting UBR4 coordinates impaired mitophagy-associated senescence and lung adenocarcinoma pathogenesis
Cellular senescence, an irreversible cell cycle arrest, plays a pivotal role in development, aging, and tumor suppression. However, the fundamental pathway coordinating senescence and neoplastic transformation remains unclear. Here, we describe the tumorigenic involvement of ubiquitin protein ligase E3 component n-recognin 4 (UBR4), an E3 ubiquitin ligase of the N-degron pathway, in lung adenocarcinoma (LUAD). Public genome databases revealed high UBR4 expression in LUAD patients, associated...
ZC3H4 safeguards genome integrity by preventing transcription-replication conflicts at noncoding RNA loci
The cellular networks that maintain genome stability encompass numerous pathways involved in all aspects of nucleic acid metabolism. Through bioinformatic analysis, we identified the Zinc Finger CCCH-Type Containing 4 protein (ZC3H4), a suppressor of noncoding RNA (ncRNA) production, as a pivotal player in this system. Experimentally, ZC3H4 deficiency led to increased DNA damage, abnormal mitosis, and cellular senescence. Biochemical analysis and super-resolution microscopy revealed that the...
Funding cuts to U.S. archaeology could imperil field’s future
A Science analysis of canceled and curtailed federal grants reveals hits to research, collections, and training