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Effects of parathyroid hormone (PTH)-related protein and PTH on osteoclasts and osteoclast precursors in vivo.

Increased production of PTH-related protein (PTHrP) and PTH is frequently responsible for hypercalcemia and its associated morbidity. However, it is unclear whether these peptides produce identical effects on cells in the osteoclast lineage in vivo. To examine the effects of continuous in vivo exposure to these factors on both the osteoclast precursors and mature osteoclasts, we inoculated Chinese hamster ovarian cells expressing PTH-(1-84), PTHrP-(1-141), or nontransfected Chinese hamster ovarian cells into nude mice. The effects of these tumors on blood ionized calcium, plasma PTH and PTHrP

Regional differences in reactive gliosis induced by substrate-bound beta-amyloid.

Regions of gliosis surround deposits of beta-amyloid peptide (beta AP) in senile plaques of Alzheimer's disease (AD). The association between reactive astrocytes and beta AP in senile plaques is most pronounced in cortex and hippocampus but not at other anatomical sites of beta AP deposition. We hypothesized that this region-specific pathology in AD could be attributed to differences in glial reactivity in different parts of the central nervous system (CNS). To test this hypothesis, we assayed astrocytes from cerebral cortex, hippocampus, cerebellum, and spinal cord for cellular responsiveness

Purine nucleosides and nucleotides stimulate proliferation of a wide range of cell types.

Presumptive astrocytes isolated from 10-day white Leghorn chick embryos, Factor VIII-positive human brain capillary endothelial cells, meningeal fibroblasts from 10-day chick embryos, Swiss mouse 3T3 cells, and human astrocytoma cell lines, SKMG-1 and U373, were rendered quiescent when placed in culture medium that contained 0 or 0.2% serum for 48 h; their proliferation was markedly reduced and they incorporated [3H]thymidine at a low rate. [3H]Thymidine incorporation and cell proliferation were induced in all types of cells by addition of guanosine, GMP, GDP, GTP, and to a lesser extent, aden

Features that distinguish age-related macular degeneration from aging.

Age-related macular degeneration (AMD) is a complex, multifactorial retinal degenerative disease that is influenced by both genetic and environmental factors. However, the strongest risk factor for AMD is advanced age. Several physiological processes are observed in aging tissues including a low level of chronic inflammation (inflammaging), changed lipid and energy metabolism, and senescence. Nevertheless, whereas everyone ages, only a subset of the population develops AMD. The purpose of this review is to delineate the differences on a cellular and molecular level between natural aging change

Unveiling the role of extracellular matrix elements and regulators in shaping ovarian cancer growth and metastasis.

Epithelial ovarian cancer (EOC) progression is determined by numerous intracellular interactions and the interplay between malignant cells, … exacerbate the pro-cancerous properties of ECM, including diabetes-associated glycation, aging, and cellular senescence. We also explore methods to therapeutically alter the properties of the ECM, which could be beneficial in ovarian cancer prevention and treatment.

The JNK signaling pathway in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) serves as the underlying pathology for various spinal degenerative conditions and is a primary contributor to low back pain (LBP). Recent studies have revealed a strong correlation between IDD and biological processes such as Programmed Cell Death (PCD), cellular senescence, inflammation, cell proliferation, extracellular matrix (ECM) degradation, and oxidative stress (OS). Of particular interest is the emerging evidence highlighting the significant involvement of the JNK signaling pathway in these fundamental biological processes of IDD. This paper explo…

State of the Art of Pharmacological Activators of p53 in Ocular Malignancies.

The pivotal role of p53 in the regulation of a vast array of cellular functions has been the subject of extensive research. The biological activity of p53 is not strictly limited to cell cycle arrest but also includes the regulation of homeostasis, DNA repair, apoptosis, and senescence. Thus, mutations in the p53 gene with loss of function represent one of the major mechanisms for cancer development. As expected, due to its key role, p53 is expressed throughout the human body including the eye. Specifically, altered p53 signaling pathways have been implicated in the development of conjunctival

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… Consequently, oxidative stress also triggers oxidative DNA damage and cellular senescence, upregulating the p16INk4a/Rb and p53/p21Cip1 pathway and finally leading to cell cycle arrest [ 123 ]. In this light, oxidative stress and p53 become key factors in the development of eye-related diseases. … Oxidative Stress-Induced Cellular Senescence in Aging Retina and Age-Related Macular Degeneration Antioxidants 2022 11 2189 10.3390/antiox11112189 36358561 PMC9686487 124. Nag S. Zhang X. Srivenugopal K.S. Wang M.H. Wang W. Zhang R. …

Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases.

Mitochondria play a central role in a plethora of processes related to the maintenance of cellular homeostasis and genomic integrity. They contribute to preserving the optimal functioning of cells and protecting them from potential DNA damage which could result in mutations and disease. However, perturbations of the system due to senescence or environmental factors induce alterations of the physiological balance and lead to the impairment of mitochondrial functions. After the description of the crucial roles of mitochondria for cell survival and activity, the core of this review focuses on the

DNA damage response and breast cancer development: Possible therapeutic applications of ATR, ATM, PARP, BRCA1 inhibition.

Breast cancer is the most common and significant cancers in females regarding the loss of life quality. Similar to other cancers, one of the etiologic factors in breast cancer is DNA damage. A plethora of molecules are responsible for sensing DNA damage and mediating actions which lead to DNA repair, senescence, cell cycle arrest and if damage is unbearable to apoptosis. In each of these, aberrations leading to unrepaired damage was resulted in uncontrolled proliferation and cancer. Another cellular function is autophagy defined as a process eliminating of unnecessary proteins in stress cases

[Dependence of carotid body structure on age in male rats (author's transl)].

The ultrastructure of the carotid corpuscle has been studied on males Wistar rats, from their birth to eighteen months. In the course of the ageing of the animal, th cytology of the constitutive elements is altered. The size of the main cells is maximal at eleven months. If the Golgi apparatus and the mitochondria do not seem very altered, the granular vesicles, the number of the ribosomes, especially these in contact with the membranes of the granular endoplasmic reticulum diminish. The vacuolisation, increased after the first month, the cells in course of degeneration, and the cellular phant

The role and mechanism of engineered nanovesicles derived from hair follicle mesenchymal stem cells in the treatment of UVB-induced skin photoaging.

BACKGROUND: Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are effective in the treatment of skin photoaging; howev … and in vitro. HFMSC-CNVs exert anti-photoaging effects by alleviating cell cycle arrest, decreasing cellular senescence and macrophage infiltration, promoting cell proliferation and extracellular matrix (ECM) production, and reducing oxidative stress by increasing the activity of antioxidant enzymes.

Biomarkers and special features of oxidative stress in the anterior segment of the eye linked to lens cataract and the trabecular meshwork injury in primary open-angle glaucoma: challenges of dual combination therapy with N-acetylcarnosine lubricant eye drops and oral formulation of nonhydrolyzed carnosine.

The implication of oxidative stress associated with increased oxidant production in mammalian and human cells characterized by the release o … cells, increased accumulation of extracellular matrix proteins (ECM), changes in the cytoskeleton, cellular senescence, and the process of subclinical inflammation. The TM is the target tissue of glaucoma in the anterior chamber, and the development and progression of glaucoma are accompanied by the accumulation of oxidative damage in this tissue. The separate studi …

Defenses against Pro-oxidant Forces - Maintenance of Cellular and Genomic Integrity and Longevity.

There has been enormous recent progress in understanding how human cells respond to oxidative stress, such as that caused by exposure to ionizing radiation. We have witnessed a significant deciphering of the events that underlie how antioxidant responses counter pro-oxidant damage to key biological targets in all cellular compartments, including the genome and mitochondria. These cytoprotective responses include: 1. The basal cellular repertoire of antioxidant capabilities and its supporting cast of facilitator enzymes; and 2. The inducible phase of the antioxidant response, notably that media

Sphere-induced reprogramming of RPE cells into dual-potential RPE stem-like cells.

BACKGROUND: The retinal pigment epithelium (RPE) has the potential to regenerate the entire neuroretina upon retinal injury in amphibians. In contrast, this regenerative capacity has been lost in mammals. The reprogramming of differentiated somatic cells into induced pluripotent stem cells (iPSCs) by viral transduction of exogenous stem cell factors has triggered a revolution in regenerative medicine. However, the risks of potential mutation(s) caused by random viral vector insertion in host genomes and tumor formation in recipients hamper its clinical application. One alternative is to immort

HIV infection-related premature immunosenescence: high rates of immune exhaustion after short time of infection.

Premature immunosenescence has been reported in different HIV scenarios. However, how premature is the HIV-related immunosenescent phenotype is still unknown. Thus, the aim of this study was to analyze the immunosenescent status of young viraemic naive HIV-infected individuals, with less than four years from infection. To this end, replicative senescence, activation and proliferation T-cell levels were analyzed in chronically HIV-infected young individuals and both, elderly and young healthy controls. We show that young HIV-infected viraemic patients, with less than four years from infection,

Selective elimination of amyloid-β-induced senescent neuroblastoma cells by Moringa oleifera leaf extract.

Accumulation of senescent cells (SnCs) in the ageing brain contributes to Alzheimer's disease (AD) progression by secreting a senescence-associated secretory phenotype (SASP) that exacerbates neuroinflammation and neurodegeneration. Senolytic agents that selectively eliminate SnCs have emerged as a potential therapeutic strategy; however, safer natural alternatives remain underexplored. In this study, we aimed to investigate the senolytic potential of Moringa oleifera leaf extract (MOL) in an in vitro AD-senescence model using SH-SY5Y cells exposed to amyloid-β (Aβ1-42) oligomers. SH-SY5Y cell

The role of redox-active iron, copper, manganese, and redox-inactive zinc in toxicity, oxidative stress, and human diseases.

Given the key importance played by the redox-active metals iron (Fe), copper (Cu), and manganese (Mn) in vital cellular processes, such as D … xidation, cause DNA damage, and lead to cell death via mechanisms such as ferroptosis, cuproptosis, cellular senescence, or inflammation. Maintaining redox homeostasis is essential for regulating numerous cellular signaling pathways. Redox-sensitive signaling pathways, such as the nuclear factor kappa B (NF-κB), mitogen-activated protein kinase kinase (MAPK), and nuc …

THE AGING PURINOME: A PURINERGIC FRAMEWORK LINKING THE HALLMARKS OF AGING TO INFLAMMAGING.

Aging is characterized by a progressive decline in cellular homeostasis accompanied by chronic, low-grade sterile inflammation, termed infla … urinergic remodeling process. We discuss how these changes may influence mitochondrial dysfunction, cellular senescence, altered intercellular communication, impaired inflammatory resolution, and age-related diseases. We further examine exercise, nutritional approaches, and pharmacological modulation of purinergic and NAD+-related pathways as potential strategies to …

Exercise and the hallmarks of cardiovascular aging.

Cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis and myocardial infarction, remain the leading cause o … omeostasis (proteostasis), genomic instability, epigenetic disturbances, mitochondrial dysfunction, cellular senescence, chronic inflammation, and dysregulated neurohormonal signaling. The mechanistic insights of exercise-induced adaptations presented in this review may provide a valuable foundation for future investigations, paving the design of tailored exercise re …

Immunometabolism: A Novel Therapeutic Target and Its Pharmacological Modulation for Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is a leading cause of low back pain (LBP) and imposes a substantial social and economic burden. Curre … on, and lipid or amino acid imbalance, drive a catabolic cascade that accelerates ECM breakdown and cellular senescence. We summarize current knowledge regarding key immune cell subsets, cytokine networks, and metabolic pathways implicated in IDD pathogenesis and IVDR, and we discuss how these immunometabolic principles are being leveraged in emerging interventions s …