Telomeres, Telomerase, and Senescence

The paper shows RAP1 inhibits DNA-PK's end joining function at telomeres by forming a complex with TRF2, preventing telomere fusions.

This study shows that loss of Atrx in a mouse sarcoma model activates the ALT telomere maintenance pathway independently of telomerase, leading to telomere instability and APB formation.

The paper investigates telomerase RNA trafficking in Aspergillus nidulans using a genetic approach and finds that telomerase assembly occurs primarily in the nucleus.

PseudoCell is a multi-valued logical regulatory network that models premature senescence dynamics and heterogeneity, validated through simulations of senescence programs and exploration of CCL11's role.

This study shows that overexpressing betaTrCP1 causes death of cisplatin-induced senescent cells by promoting proteasomal degradation of p21 CIP1 through NPM1 retention in nucleoli.

This study shows nicotinamide induces reversible senescence in glioblastoma cells by reprogramming metabolism and reducing SOX2, with senescent cells retaining tumor-forming ability.

This study identifies ADAM19 as a modulator of the senescence-associated secretory phenotype (SASP) and shows that its inhibition reduces gut permeability and senescence markers in multiple species.

The paper identifies structural interactions between yeast CST and Pol/primase complexes that are essential for telomere maintenance and protection, showing their joint role in telomere regulation.

This paper shows telomere length regulates hTERT expression by modulating TRF2 binding and PRC2-mediated repression, revealing a self-regulatory mechanism in cancer.

The paper identifies a CPC-shelterin-BTR axis that regulates mitotic telomere deprotection through phosphorylation events and DDR activation.

Senolytic drugs reduce low back pain by eliminating senescent cells and decreasing inflammatory factors in the intervertebral disc and spinal cord.

This study identifies a mitochondria-regulated p53 circuit that links genomic instability and inflammation in senescent cells, showing p53 suppresses inflammation without affecting cell cycle arrest.

This study investigates time-dependent changes in osteocyte cytoskeleton mechanics and morphology due to senescence-associated secretory phenotype factors, identifying biophysical markers for senescent osteocytes.

SenePy identifies cell-type specific senescence signatures from single-cell data, improving senescent cell detection in vivo and revealing increased senescence in diseases like COVID-19 and myocardial infarction.

This study shows that inhibiting ER-mitochondria Ca2+ flux is a new target for senolysis in therapy-induced senescence.

The paper develops an Optical Pooled Screen (OPS) assay using telomeric native DNA FISH to measure ALT pathway activity and identifies regulators of the ALT pathway.

The paper identifies new senescent cell anti-apoptotic pathways and senolytics using transcriptomic data and network-based methods, validating Fluorouracil's senolytic activity through multiple targets.

The paper uses single-cell proteomics to identify two distinct senescence subpopulations with different SASP characteristics during long-term stress.

This study identifies a misfolded CR4/5 conformation in hTR that is not required for hTERT binding and is detrimental to telomerase activity.

The paper identifies AP2A1 upregulation in senescent human fibroblasts, which strengthens focal adhesions via integrin β1 translocation along stress fibers, maintaining large cell size.

This study shows that substrate stiffness influences doxorubicin-induced senescence and secretory profiles in human pulmonary fibroblasts, with collagen enrichment observed in high-stiffness conditions.

This study shows that centromere inactivation during aging in human cells can be reversed by inhibiting p53 and LSD1/KDM1A, restoring centromeric proteins and transcripts.

This paper identifies SUB1 as a vulnerability in ALT cancer cells by showing it mitigates telomeric replication stress and that its depletion synergizes with replication stress-inducing therapies.

This study identifies YARS as a transcriptional regulator that promotes senescence escape by enhancing LIN9 expression through epigenetic modifications.

This study identifies Mediator complex subunits, Scalloped, and E2F1-Dp as regulators of telomeric retrotransposon transcription and telomere length in Drosophila, linking TR expression to the cell cycle.

This paper develops a machine learning model using telomeric data to predict tumor status across 33 cancer types, achieving 82.62% accuracy.

This study identifies senescent features in lymph node stromal cells from RA patients and shows that dasatinib treatment partially reverses these features.

The paper identifies TERRA's ability to bind non-telomeric DNA via R-loops, suggesting a role in genome-wide gene regulation.

This study identifies novel genes that modulate the ALT pathway using a high-throughput imaging screen, revealing both promoting and inhibiting factors and demonstrating pharmacological modulation potential.

This paper shows that inhibiting glutaminase 1 (GLS1) kills senescent melanoma cells induced by CDK4/6 inhibitors, even when those cells are resistant to BRAF inhibitors.