Journal of Cellular Physiology最新文献

This study explored the role of telomere attrition in astrocytic senescence by pharmacologically inhibiting telomerase activity in human induced pluripotent stem cell-derived astrocytes. Treatment with the telomerase inhibitor BIBR1532 (BIBR) during differentiation induced hallmark features of senescence, including nuclear lamina abnormalities, enhanced senescence-associated β-galactosidase activity, increased replication arrest and DNA damage, altered reactive oxygen species homeostasis in mitochondria, accompanied by significant shortening of relative telomere length. Despite these senescence related characteristics, BIBR-treated astrocytes exhibited limited changes in the expression of senescence-associated secretory phenotype-related genes. Moreover, their key functional properties, such as glutamate uptake, synaptic vesicle clearance, mitochondrial membrane potential and morphology remain comparable to those of control astrocytes. These findings suggest that the presence of classical senescence markers does not necessarily lead to functional impairment and that BIBR-induced senescence in astrocytes may represent an early or transitional phase, where classical senescence markers emerge without substantial functional decline. Our results reinforce the notion that while telomere attrition is a major cellular senescence driver, its onset may not be attributed to a single stressor but rather to a complex interplay of cellular stress pathways. This study provides valuable insights into the mechanisms underlying astrocytic senescence and underscores the need for further research on the molecular basis of its occurrence and functional implications.

Osteoporosis, fragility fractures, and pathologic fractures are increasingly recognized as long-term complications in cancer survivors. Women are more susceptible to bone loss than men, and breast cancer is the most common malignancy in women. In this population, bone health is a critical concern due to both therapy-induced bone loss and a high propensity for skeletal metastasis. Antiresorptive agents are widely used; however, their known adverse effects and limited capacity to rapidly reduce fracture risk in high-risk individuals have led to growing support for the early use of osteoanabolic therapies. Among these, intermittent administration of parathyroid hormone [PTH (1–34)] has demonstrated clinical efficacy in reducing fracture risk by activating the PTH 1 receptor in osteoblasts. However, its safety and mechanistic relevance in the context of breast cancer remain poorly understood. This review outlines the osteoblast-specific signaling pathways of PTH (1–34) and includes our recent research that identified p21-activated kinase 4 as a downstream effector linking canonical cyclic adenosine monophosphate-protein kinase A signaling to Wnt/β-catenin activation. Additionally, it explores the potential implications of PTH (1–34) in the context of breast cancer-related bone metastasis.

Skin aging is a complex biological process driven by the dynamic interplay of cellular senescence, molecular dysfunction, and microenvironmental remodeling. The aging microenvironment acts as both a consequence and a driver of skin aging, creating a vicious cycle that exacerbates inflammation, oxidative stress, and barrier dysfunction. An in-depth exploration of the aging skin microenvironment plays a revolutionary role in the field of skin anti-aging and holds promise for the discovery of novel and feasible targets for skin anti-aging. This review systematically elaborates the aging skin microenvironment through a framework of six interconnected components: (1) inflammaging and immune cell dysfunction, (2) extracellular matrix dysregulation, (3) intercellular communication and extracellular vesicles defect, (4) physical microenvironmental alterations, (5) stem cell exhaustion, and (6) microbiome dysbiosis. These components collectively establish a self-reinforcing network that perpetuates structural degradation, functional decline, and impaired regenerative capacity.

In mammals, the establishment of primordial follicles (PFs) occurs in an orderly manner and is an energy-demanding process. However, the mechanisms underlying the supply and demand of energy metabolism during primordial follicle formation, particularly glycolysis and oxidative phosphorylation (OXPHOS) signaling, remain poorly understand. Herein, based on the analyses of single-cell RNA sequencing (scRNA-seq) data from mouse ovarian tissues, gene expression associated with glycolysis and OXPHOS signaling were dynamically changed along pseudotime trajectory in pre-granulosa (PG) cells and oocytes following cell development and PF formation. The molecules related to glycolysis and OXPHOS signaling exhibited dynamic expression patterns in mouse ovarian tissues following PF formation, with distinct expression levels and location in somatic cells and oocytes. The dysfunctions of mitochondrial and glucose metabolic patterns using glycolysis inhibitor (2-Deoxy-Dglucose, 2-DG) or OXPHOS signaling inhibitor (metformin, MET) significantly inhibited PF formation, disordered oocyte development, downregulated key gene expression, impaired the recruitment and maintenance of PG cells, and altered cell proliferation and apoptosis. Collectively, these results demonstrate that cellular metabolic patterns are diverse and dynamically regulate in oocytes and PG cells during PF formation of mice, and glucose metabolism is essential for PF formation and its disruption inhibits PF formation.

During malignancy, metabolic reprogramming is critical for cancer cells to survive and thrive in nutrient- and oxygen-poor conditions. Autophagy is a catabolic process through which intracellular components are degraded to support cells upon exposure to stressful conditions. While autophagy is protective during early cancer initiation, tumor cells may initiate cell-intrinsic and cell-extrinsic autophagy to support their survival in later stages of cancer. As autophagy is present at low levels in most tissues under homeostasis and upregulated in malignancy, there has been great interest in targeting the autophagy pathway for cancer therapy. Here, we discuss the mechanisms through which autophagy and autophagy-related proteins act to limit carcinogenesis. We then review pro-tumor roles for autophagy in tumor cells as well as in components of the tumor microenvironment. Finally, we discuss autophagy-targeted approaches for cancer therapy. This review article highlights autophagy as a key player in cell metabolism that is often leveraged to support cancer progression and as a potential therapeutic target in a variety of cancer types.

Milk is a natural product synthesized and secreted by Bovine mammary epithelial cells (BMECs), providing the nutrients needed for the growth and development of calves. At the same time, it is also one of the common beverages in our daily life. The research on the expansion mechanisms of BMECs is of great significance for increasing dairy yield. DNAJA1 pertains to the HSP40 family (alternatively called DNAJ proteins). As an essential mammalian molecular chaperone, this protein features a structurally distinctive J-domain region enabling functional coordination with HSP70 (HSPA). However, the expression mechanism and biological function of DNAJA1 in BMECs remain unclear. This investigation demonstrates DNAJA1's critical involvement in methionine (Met) and leucine (Leu)-modulated BMEC proliferation. Experimental findings reveal that both Met and Leu stimulate BMEC proliferation, with DNAJA1 similarly exerting a positive regulatory influence on cellular multiplication. Within BMECs, Met and Leu augment proliferation by activating the PI3K-AKT-DNAJA1 signaling axis. Concurrently, an interaction between DNAJA1 and TAK1 potentially contributes further to regulating this proliferative process.