Abdominal aortic aneurysm (AAA) is a prevalent condition characterized by the weakening and bulging of the abdominal aorta. This study aimed to investigate the impact of a stiff matrix on vascular smooth muscle cells (VSMCs) in AAA development. Bioinformatics analysis revealed that differentially expressed genes (DEGs) in VSMCs of an AAA mouse model were enriched in cellular senescence and related pathways. To simulate aging‐related changes, VSMCs were cultured on stiff matrices, and compared to those on soft matrices, the VSMCs cultured on stiff matrices exhibited cellular senescence. Furthermore, the mutual distance between mitochondria and endoplasmic reticulum (ER) in VSMCs was increased, indicating altered mitochondria–endoplasmic reticulum contacts (MERCs). The observed upregulation of reactive oxygen species (ROS) levels, antioxidant gene expression, and decreased mitochondrial membrane potential suggested the presence of mitochondrial dysfunction in VSMCs cultured on a stiff matrix. Additionally, the induction of ER stress‐related genes indicated ER dysfunction. These findings collectively indicated impaired functionality of both mitochondria and ER in VSMCs cultured on a stiff matrix. Moreover, our data revealed that high lipid levels exacerbated the effects of high matrix stiffness on VSMCs senescence, MERC sites, and mitochondria/ER dysfunction. Importantly, treatment with the antilipemic agent CI‐981 effectively reversed these detrimental effects. These findings provide insights into the role of matrix stiffness, mitochondrial dysfunction, ER stress, and lipid metabolism in AAA development, suggesting potential therapeutic targets for intervention.

Chemoresistance remains a major obstacle in prostate cancer therapy. This study demonstrates that high extracellular matrix stiffness promotes chemoresistance by disrupting mitochondrial-nuclear communication. Culturing prostate cancer cells on polyacrylamide hydrogels of varying stiffness revealed that a high-stiffness environment promotes mitochondrial fusion and enhances function. Mechanistic investigations revealed that high matrix stiffness activates YAP, leading to dysregulation of the Hippo signaling pathway, which subsequently upregulates the expression of OPA1 and induces mitochondrial fusion. This fusion triggers a reprogramming of glutamine metabolism. The resulting metabolite, α-ketoglutarate, activated DNA demethylases TET1 and TET3, causing epigenetic modifications of YAP target genes and further exacerbating Hippo pathway dysregulation. Together, this establishes a YAP-OPA1-TET1/3-mediated positive feedback loop between the nucleus and mitochondria that drives drug resistance. Crucially, targeting OPA1 disrupted this loop and reversed stiffness-induced chemoresistance. These findings reveal a novel mitochondrial-nuclear communication, offering new insights for overcoming chemoresistance in prostate cancer.

Aging is characterized by a gradual deterioration of the physiological integrity of cells, tissues, and organs, resulting in a decrease in the body’s physiological functions and an acceleration of the onset of age-related diseases, ultimately leading to death. The aging of the liver, which is a critical metabolic organ, is closely linked to various chronic liver diseases, such as hepatitis, liver fibrosis, and cirrhosis, and it exacerbates their prognosis and is a primary risk factor for their development at all stages. Therefore, a comprehensive understanding of the causes, mechanisms, and potential therapeutic targets associated with liver aging holds significant clinical importance for delaying or potentially reversing liver aging and for treating chronic liver diseases. Stem cells, which are potential anti-aging agents, present a promising and effective alternative for managing liver aging. In this review, we systematically assess the driving factors, characteristics, and underlying mechanisms of liver aging. We then discuss the current status of the use of stem cells to mitigate liver senescence and address related liver diseases. The review reveals that a stem cell-based approach represents a promising therapeutic strategy for combating liver aging and associated diseases.

Fibrosis is a hallmark of the tumor microenvironment in many solid cancers, driving tumor progression, immune evasion, and treatment resistance; however, the molecular and cellular mechanisms underlying fibrogenesis—particularly stromal–immune crosstalk across organs—remain incompletely understood, compounded by organ-specific heterogeneity and a lack of reliable immune-related biomarkers. To address this, we performed an integrative single-cell RNA sequencing (scRNA-seq) analysis of fibrotic tissues from four major organs—liver, lung, heart, and kidney—alongside non-fibrotic controls, applying unsupervised clustering, trajectory inference, cell–cell communication modeling, and gene set variation analysis (GSVA) to map the fibro-immune landscape. Our analysis revealed both conserved and organ-specific features: fibroblasts were the dominant extracellular matrix (ECM)-producing cells in liver and lung, whereas endothelial-derived stromal populations prevailed in heart and kidney. Immune profiling uncovered distinct infiltration patterns—macrophages displayed organ-specific polarization states; T cells were enriched for tissue-resident subsets in lung and mucosal-associated invariant T (MAIT) cells in liver; and B cells exhibited marked heterogeneity, including a pathogenic interferon-responsive subset prominent in pulmonary fibrosis. GSVA further identified divergent signaling programs across organs and lineages, including TGF-β/TNF-α in the heart, NOTCH/mTOR in the kidney, glycolysis/ROS in the lung, and KRAS/interferon pathways in the liver. Cell–cell communication analysis highlighted robust crosstalk between macrophages, T/B cells, and stromal cells mediated by collagen, laminin, and CXCL signaling axes. Together, this cross-organ atlas delineates a highly heterogeneous fibro-immune ecosystem in human fibrotic diseases, revealing shared mechanisms alongside organ-specific regulatory networks, with immediate translational implications for precision anti-fibrotic therapy, immunomodulatory drug repurposing, and the development of context-specific biomarkers for clinical stratification and therapeutic monitoring.