Soon Sang Park

Cellular senescence is accompanied by widespread chromatin and transcriptional remodeling, but datasets that capture these changes across intermediate stages of replicative senescence remain limited. Here, we present an integrated bulk RNA-seq and ATAC-seq resource generated from primary human colonic fibroblasts spanning three replicative states: early-passage young cells, intermediate pre-senescent cells, and late-passage senescent cells. This serial design enables not only endpoint comparison between young and senescent cells but also stepwise evaluation of molecular changes during senescence progression. Bulk RNA-seq profiles captured transcriptome-wide alterations across the three states, while ATAC-seq defined corresponding changes in chromatin accessibility. By integrating promoter-associated accessibility with gene expression, we generated a gene-level multi-omic resource for evaluating concordant and discordant chromatin-transcription relationships across senescence transitions. The dataset also supports downstream analyses including pathway enrichment and transcription factor activity inference. Together, this dataset provides a useful resource for studying chromatin accessibility, transcriptional regulation, and their coupling during the progression of replicative senescence in human colonic fibroblasts.

Purpose: Hepatic steatosis influences the hepatic microenvironment, thereby affecting the prognosis of colorectal cancer (CRC). This study aimed to evaluate whether pre-existing hepatic steatosis is associated with survival outcomes in patients with CRC and whether statin use after CRC diagnosis is associated with improved survival in patients with hepatic steatosis.Methods: A nationwide retrospective cohort study was conducted using data from the Korea- Clinical data Utilization network for Research Excellence (K-CURE) Cancer Public Library from 2012 to 2021. Newly diagnosed patients with CRC aged 40 to 80 years with localized or regional disease were included. Hepatic steatosis was defined as a fatty liver index ≥60. The primary analysis evaluated the association between hepatic steatosis, CRC, and all-cause mortality. Secondary analysis was restricted to patients with hepatic steatosis, and statin users and non-users were compared using an active-comparator design. Cox proportional hazards models, Fine–Gray competing risk models, and propensity score matching were applied.Results: In 57,368 patients with CRC, hepatic steatosis was associated with an increased risk of CRC-specific mortality and all-cause mortality. After propensity score matching, the adjusted hazard ratios (aHR) for CRC-specific mortality were 1.283 (95% confidence interval [CI], 1.055 to 1.561) and 1.171 (95% CI, 1.001 to 1.371) for all-cause mortality. In a secondary analysis of patients with hepatic steatosis, statin use after CRC diagnosis was associated with a reduced risk of CRC-specific mortality (aHR, 0.462; 95% CI, 0.232 to 0.920) and all-cause mortality (aHR, 0.504; 95% CI, 0.290 to 0.877).Conclusion: Pre-existing hepatic steatosis is associated with poor survival in patients with CRC. In patients with hepatic steatosis, statin use after CRC diagnosis was associated with improved cancer-specific and overall survival. These findings suggest that hepatic steatosis may be a clinically relevant prognostic factor in CRC and that statins may have potential survival benefits in this subgroup.

Gastroesophageal Reflux Disease (GERD) is characterized by the regurgitation of stomach contents. Recent research indicates that acid reflux may disrupt the homeostasis of the middle and inner ear through the Eustachian tube. Given this context, we hypothesized that an association between GERD and tinnitus may exist due to the imbalance of the middle and inner ear caused by acid reflux. To explore this connection, we conducted a retrospective cohort study involving 669,159 patients registered in the National Health Insurance Service-National Sample Cohort (2012–2019) in South Korea. Our data showed that GERD and tinnitus are highly associated. Nevertheless, the use of proton pump inhibitor medication in GERD patients did not show a significant decrease in the onset of tinnitus.

Cellular senescence, recognized as a key hallmark of aging, leads to the accumulation of senescent cells in various tissues over time. While the detrimental effects of these cells on age-related pathological conditions are well-documented, there is still limited information about how senescent cells are distributed in normal tissues of both young and aged organs. Our research indicates that fully senescent p16^INK4A+ cells are rarely identified in the parenchyma of organic tissues and in the stromal cells crucial for structural maintenance, such as fibroblasts and smooth muscle cells. Instead, p16^INK4A+ cells are more commonly found in immune cells, whether they reside in the organ or are infiltrating. Notably, p16^INK4A+ senescent T cells have been observed to induce apoptosis and inflammation in colonic epithelial cells through Granzyme A-PARs signaling, compromising the integrity of the epithelial lining. This study showed that the senescence of immune cells could affect the phenotypical change of the parenchymal cells in the elderly and suggests that targeting immunosenescence might be a strategy to control functional decline in this population.

The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed “mid-old status” cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Remarkably, the microenvironmental change and the functional decline of mid-old cells could be reversed by a young cell-originated protein, SLIT2. Our data identify functional reversion of mid-old cells as a potential method to prevent or ameliorate aspects of aging-related tissue dysfunction.

Background: Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells.Methods: Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated β-galactosidase (SA-β-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase–tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-β-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model.Results: Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-β-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-β-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength.Conclusions: Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.

(1) Background: Currently, limited data are available regarding the relationship between epicardial fat and plaque composition. The aim of this study was to assess the relationship between visceral fat surrounding the heart and the lipid core burden in patients with coronary artery diseases; (2) Methods: Overall, 331 patients undergoing coronary angiography with combined near-infrared spectroscopy and intravascular ultrasound imaging were evaluated for epicardial adipose tissue (EAT) thickness using transthoracic echocardiography. Patients were divided into thick EAT and thin EAT groups according to the median value; (3) Results: There was a positive correlation between EAT thickness and maxLCBI_4mm, and maxLCBI_4mm was significantly higher in the thick EAT group compared to the thin EAT group (437 vs. 293, p < 0.001). EAT thickness was an independent predictor of maxLCBI_4mm ≥ 400 along with age, low-density lipoprotein-cholesterol level, acute coronary syndrome presentation, and plaque burden in a multiple linear regression model. Receiver operating characteristic curve analysis showed that EAT thickness was a predictor for maxLCBI_4mm ≥ 400; (4) Conclusions: In the present study, EAT thickness is related to the lipid core burden assessed by NIRS-IVUS in patients with CAD which suggests that EAT may affect the stability of the plaques in coronary arteries.

Senescent cells in cancer tissue, including senescent fibroblasts and macrophages, have been reported to increase the malignant potency of cancer cells by secreting senescence-associated secretory phenotype (SASP). Otherwise, Senescence of tumor cells has been believed to inhibit tumor growth by halting the massive proliferation and increasing the chances of immune clearance. In particular, senescent tumor cells (STCs) have been thought that they rarely exist in carcinomas because oncogene-induced senescence needs to be overcome for protumorigenic cells to become malignant. However, recent studies have revealed that a considerable number of STCs are present in cancer tissue, even in metastatic sites. In fact, STCs are widely involved in cancer progression by leading to collective invasion and building a cytokine barrier to protect nonsenescent tumor cells from immune attack. Furthermore, therapy-induced STCs can induce tumor progression and recurrence by increasing stemness. However, obscure causative factors and their heterogeneity in various cancers make it difficult to establish the physiological role of STCs. Here, we summarize and review the current knowledge of the pathophysiology and role of STCs. We also outline the current status of therapeutic strategies for directly removing STCs or modulating the SASPs to maximize the positive functions of STCs while suppressing the negative functions.