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Cx43 enhances response to BRAF/MEK inhibitors by reducing DNA repair capacity

5 months 3 weeks ago
BRAF and MEK inhibitors (BRAF/MEKi) have radically changed the treatment landscape of advanced BRAF mutation-positive tumours. However, limited efficacy and emergence of drug resistance are major barriers for successful treatments. Here, by using relevant preclinical models, we find that Connexin43 (Cx43), a protein that plays a role in cell-to-cell communication, enhances the effectiveness of BRAF/MEKi by recruiting DNA repair complexes to lamin-associated domains and promoting persistent DNA...
Adrián Varela-Vázquez

Dimerization and substrate recognition of human taurine transporter

5 months 3 weeks ago
Taurine is a conditionally essential nutrient and one of the most abundant amino acids in humans, with diverse physiological functions. The cellular uptake of taurine is primarily mediated by the taurine transporter (TauT), and its dysfunction leads to retinal regeneration, cardiomyopathy, neurological and aging-associated disorders. Here we determine structures of TauT in two states: the apo inward-facing open state and the occluded state bound with substrate taurine or γ-aminobutyric acid...
Yimin Zhang

Walking into aging: real-world mobility patterns and digital benchmarks from the InCHIANTI Study

5 months 3 weeks ago
Mobility is a cornerstone of health and quality of life, particularly in older adults. Digital mobility outcomes (DMOs) from real-world walking data offer crucial insights into the functional status and early markers of mobility decline. This study provides reference values for walking activity, pace, rhythm, and gait bout-to-bout variability in community-dwelling older adults and evaluates the effects of age, sex, height, and weight on these parameters. Using data from 200 older adults (aged...
Jose Albites-Sanabria

Increased genetic protection against Alzheimer's disease in centenarians

5 months 3 weeks ago
We constructed a polygenic protective score specific to Alzheimer's disease (AD PPS) based on the current literature among the participants enrolled in five studies of healthy aging and extreme longevity in the USA, Europe, and Asia. This AD PPS did not include variants on apolipoprotein E (APOE) gene. Comparisons of AD PPS in different data sets of healthy agers and centenarians showed that centenarians have stronger genetic protection against AD compared to individuals without familial...
Harold Bae

Gene expression and co-expression heterogeneity patterns and biodemography analyses during the cell cycle encourage aging studies in archaea

5 months 3 weeks ago
One of the prokaryotic partners at the origin of eukaryotes was an archaeon, but do archaea age, and if so, how? Uncovering aging in Archaea might provide more general clues about cellular senescence and rejuvenation and their origins. To fill this knowledge gap, we focused on Saccharolobus islandicus, a model archaeon for which the cell cycle can be synchronized and controlled. We generated longitudinal transcriptomes of synchronized S. islandicus populations that capture typical expression and...
Yuping Dai

SARS-CoV-2 induces Alzheimer's disease-related amyloid-beta pathology in ex vivo human retinal explants and retinal organoids

5 months 3 weeks ago
While the etiology of Alzheimer's disease remains unknown, there is growing support for the amyloid-β antimicrobial hypothesis. Amyloid-β, the main component of amyloid plaques in Alzheimer's disease, has been shown to be generated in the presence of microbes. Entrapment of microbes by aggregated amyloid-β may serve as an innate immune response to pathogenic infections. To understand the association of amyloid-β plaques and pathogenic infections in the central nervous system, we obtained viable...
Sean J Miller

Effects of positive sex education and pelvic floor strengthening program on sexual and pelvic health among youngest old: a randomized controlled trial

5 months 3 weeks ago
CONCLUSIONS: The sexual program which handled comprehensive and interdisciplinary approach could offer more than just addressing sexual function. Due to the unreached significant increase in sexual esteem and sexual quality of life and lack of knowledge about these, there is a need to have future studies. It is essential for national health policies to incorporate and act on interdisciplinary approach to sexuality in older adults.
Ayse Deliktas Demirci

Determinants of waiting times for surgery in older patients with hip fractures: a two-center retrospective study in Japanese acute care hospitals

5 months 3 weeks ago
CONCLUSIONS: Both patient- and healthcare system–related factors were associated with delayed surgery for hip fractures in older adults. Although a reimbursement incentive has been introduced to promote early surgery, real-world challenges, including preoperative risk factors and hospital resources, continue to affect surgical timing. These findings could help inform strategies to enhance timely surgical care for older patients with hip fractures in aging societies.
Yunhan Ji

Health-related needs and indicators of an age-friendly city: a survey from the perspective of older adults in a province in Southeastern Iran

5 months 3 weeks ago
CONCLUSION: This study offers valuable insights into the health-related needs and indicators of an age-friendly city for older adults in a province in Iran. The results can guide managers, policymakers, and planners in developing effective strategies for elderly care at both national and regional levels.
Jamileh Farokhzadian

TET2-mutant myeloid cells mitigate Alzheimer's disease progression via CNS infiltration and enhanced phagocytosis in mice

5 months 3 weeks ago
Clonal hematopoiesis (CH) is associated with many age-related diseases, but its interaction with Alzheimer's disease (AD) remains unclear. Here, we show that TET2-mutant CH is associated with a 47% reduced risk of late-onset AD (LOAD) in the UK Biobank, whereas other drivers of CH do not confer protection. In a mouse model of AD, transplantation of Tet2-mutant bone marrow reduced cognitive decline and β-amyloid plaque formation, effects not observed with Dnmt3a-mutant marrow. Bone-marrow-derived...
Katie A Matatall