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Bidirectional associations between biological aging, cardiovascular health, and cardiovascular risk: findings from the INSPIRE-T lifespan cohort
Chronological age is a common and non-modifiable factor for chronic disease, but does not fully explain age-related changes. Biological clocks have been developed to explore biological aging mechanisms. They could help identify protective factors against accelerated aging and associated diseases. We aim to assess the association between reduced epigenetic or inflammatory aging and ideal cardiovascular health or cardiovascular risk. We conducted a cross-sectional analysis of participants from the...
Nuclear speckle dynamics are controlled by polyphosphate inhibition of CLK proteins
Nuclear speckles (NS) are membraneless nuclear organelles that act as critical hubs for pre-messenger RNA splicing. Defects in splicing are linked to several human diseases, including cancer, Alzheimer's disease, and dystrophies. While CLK kinases regulate the mobilization of splicing factors from NS, the molecular mechanisms underlying NS assembly and dissolution remain unclear. Using an adaptation of the Biotinylation by Antibody Recognition technique, we identified polyphosphate (polyP) as a...
Trophoblast aging driven by IL33 deficiency elevates recurrent pregnancy loss risk through SNAP29 lactylation-mediated autophagy impairment
Emerging evidence implicates premature placental senescence as a central driver of pregnancy complications, though its underlying mechanisms remain elusive. Here, we report marked downregulation of IL33 (interleukin 33) in villi from unexplained recurrent pregnancy loss (URPL) patients, concomitant with elevated trophoblast senescence. More importantly, il33 knockout mice exhibited placental senescence and impaired trophoblast invasion. Mechanistically, senescent trophoblasts displayed metabolic...
RPA hyperphosphorylation hinders the resolution of R-loops and G-quadruplex-associated R-loops during RAS-driven senescence
Activation of RAS oncogenes in normal cells triggers a stable cell cycle arrest known as RAS-induced senescence (RIS), marked by persistent DNA damage and extensive epigenetic remodeling. Although bypassing RIS promotes tumorigenesis, the molecular mechanisms underlying this transition remain poorly defined. Here, we demonstrate that RIS cells accumulate high levels of R-loops-three-stranded DNA-RNA hybrids-that frequently co-localize with DNA G-quadruplexes formed on the non-template DNA...
Subtle-seq reveals frequent ageing-associated chromosome fragmentation on nucleosome core DNA
Telomere healing seals the broken ends of DNA double-strand breaks by adding de novo telomeres. In the ciliate Paramecium, telomere healing results in chromosome fragmentation, which ultimately leads to clonal ageing. Despite its importance, where and how chromosomes fragment and undergo telomere healing, and to what extent sequence preferences exist, remain poorly understood. To investigate chromosome fragmentation, we enriched for telomere-containing sequences from the complex, highly...