During the aging process, cells can enter cellular senescence, a state in which cells leave the cell cycle but remain viable. This mechanism is thought to protect tissues from propagation of damaged cells and the number of senescent cells has been shown to increase with age. The speed of aging determines the lifespan of a species and it varies significantly in different species. To assess the progress of cellular senescence during lifetime, we performed a comparative longitudinal study using histochemical detection of the senescence-associated beta-galactosidase as senescence marker to map the staining patterns in organs of the long-lived zebrafish and the short-lived turquoise killifish using light- and electron microscopy. We compared age stages corresponding to human stages of newborn, childhood, adolescence, adult and old age. We found tissue-specific but conserved signal patterns with respect to organ distribution. However, we found dramatic differences in the onset of tissue staining. The stained zebrafish organs show little to no signal at newborn age followed by a gradual increase in signal intensity, whereas the organs of the short-lived killifish show an early onset of staining already at newborn stage, which remains conspicuous at all age stages. The most prominent signal was found in liver, intestine, kidney and heart, with the latter showing the most prominent interspecies divergence in onset of staining and in staining intensity. In addition, we found staining predominantly in epithelial cells, some of which are post-mitotic, such as the intestinal epithelial lining. We hypothesize that the association of the strong and early-onset signal pattern in the short-lived killifish is consistent with a protective mechanism in a fast growing species. Furthermore, we believe that staining in post-mitotic cells may play a role in maintaining tissue integrity, suggesting different roles for cellular senescence during life.
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http://dx.doi.org/10.4081/ejh.2024.3977 | DOI Listing |
Adv Sci (Weinh)
January 2025
Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, 210029, China.
Patellar dysplasia (PD) can cause patellar dislocation and subsequent osteoarthritis (OA) development. Herein, a novel ABCA6 mutation contributing to a four-generation family with familiar patellar dysplasia (FPD) is identified. In this study, whole exome sequencing (WES) and genetic linkage analysis across a four-generation lineage presenting with six cases of FPD are conducted.
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January 2025
Department of Hepatic Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Polybromo-1 (PBRM1) serves as a crucial regulator of gene transcription in various tumors, including intrahepatic cholangiocarcinoma (iCCA). However, the exact role of PBRM1 in iCCA and the mechanism by which it regulates downstream target genes remain unclear. This research has revealed that PBRM1 is significantly downregulated in iCCA tissues, and this reduced expression is linked to aggressive clinicopathological features and a poor prognosis.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
State Key Laboratory of Frigid Zone Cardiovascular Diseases, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China.
Abdominal aortic aneurysm (AAA) is the most prevalent dilated arterial aneurysm that poses a significant threat to older adults, but the molecular mechanisms linking senescence to AAA progression remain poorly understood. This study aims to identify cellular senescence-related genes (SRGs) implicated in AAA development and assess their potential as therapeutic targets. Four hundred and twenty-nine differentially expressed genes (DEGs) were identified from the GSE57691 training set, and 867 SRGs were obtained.
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January 2025
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
Cytokinins are plant hormones that regulate cell growth and differentiation. In particular, zeatin (ZTN) delays cellular senescence of human fibroblasts and keratinocytes and exhibits anticancer activity. Chemotherapy-induced anemia is a major side effect of anticancer therapy secondary to premature senescence of red blood cells (RBCs).
View Article and Find Full Text PDFResearch (Wash D C)
January 2025
State Key Laboratory of Genetic Engineering, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, Center for Evolutionary Biology, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai 200438, China.
Drug resistance to a single agent is common in cancer-targeted therapies, and rational drug combinations are a promising approach to overcome this challenge. Many Food and Drug Administration-approved drugs can induce cellular senescence, which possesses unique vulnerabilities and molecular signatures. However, there is limited analysis on the effect of the combination of cellular-senescence-inducing drugs and targeted therapy drugs.
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