Search results for "SENESCENCE"

Decreased response to acetylcholine during aging of Aplysia neuron R15

2013

How aging affects the communication between neurons is poorly understood. To address this question, we have studied the electrophysiological properties of identified neuron R15 of the marine mollusk Aplysia californica . R15 is a bursting neuron in the abdominal ganglia of the central nervous system and is implicated in reproduction, water balance, and heart function. Exposure to acetylcholine (ACh) causes an increase in R15 burst firing. Whole-cell recordings of R15 in the intact ganglia dissected from mature and old Aplysia showed specific changes in burst firing and properties of action potentials induced by ACh. We found that while there were no significant changes in resting membrane p…

Carbocysteine regulates innate immune responses and senescence processes in cigarette smoke stimulated bronchial epithelial cells

2013

Cigarette smoke represents the major risk factor for chronic obstructive pulmonary disease (COPD). Cigarette smoke extracts (CSE) alter TLR4 expression and activation in bronchial epithelial cells. Carbocysteine, an anti-oxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on TLR4 expression and on the TLR4 activation downstream events are largely unknown. This study was aimed to explore whether carbocysteine, in a human bronchial epithelial cell line (16-HBE), counteracted some pro-inflammatory CSE-mediated effects. In particular, TLR4 expression, LPS binding, p21 (a senescence marker), IL-8 mRNA and…

Specific Irreversible Cell-Cycle Arrest and Depletion of Cancer Cells Obtained by Combining Curcumin and the Flavonoids Quercetin and Fisetin.

2022

Background: Induced senescence could be exploited to selectively counteract the proliferation of cancer cells and target them for senolysis. We examined the cellular senescence induced by curcumin and whether it could be targeted by fisetin and quercetin, flavonoids with senolytic activity. Methods: Cell-cycle profiles, chromosome number and structure, and heterochromatin markers were evaluated via flow cytometry, metaphase spreads, and immunofluorescence, respectively. The activation of p21waf1/cip1 was assessed via RT-qPCR and immunoblotting. Senescent cells were detected via SA-β-Galactosidase staining. Results: We report that curcumin treatment specifically triggers senescence in cancer…

Benzo[a]pyrene represses DNA repair through altered E2F1/E2F4 function marking an early event in DNA damage-induced cellular senescence

2020

AbstractTranscriptional regulation of DNA repair is of outmost importance for the restoration of DNA integrity upon genotoxic stress. Here we report that the potent environmental carcinogen benzo[a]pyrene (B[a]P) activates a cellular DNA damage response resulting in transcriptional repression of mismatch repair (MMR) genes (MSH2, MSH6, EXO1) and of RAD51, the central homologous recombination repair (HR) component, ultimately leading to downregulation of MMR and HR. B[a]P-induced gene repression is caused by abrogated E2F1 signalling. This occurs through proteasomal degradation of E2F1 in G2-arrested cells and downregulation of E2F1 mRNA expression in G1-arrested cells. Repression of E2F1-me…

The role of reactive oxygen species and subsequent DNA-damage response in the emergence of resistance towards resveratrol in colon cancer models

2014

AbstractIn spite of the novel strategies to treat colon cancer, mortality rates associated with this disease remain consistently high. Tumour recurrence has been linked to the induction of resistance towards chemotherapy that involves cellular events that enable cancer cells to escape cell death. Treatment of colon cancer mainly implicates direct or indirect DNA-damaging agents and increased repair or tolerances towards subsequent lesions contribute to generate resistant populations. Resveratrol (RSV), a potent chemosensitising polyphenol, might share common properties with chemotherapeutic drugs through its indirect DNA-damaging effects reported in vitro. In this study, we investigated how…

Administration of a Synbiotic to Free-Living Elderly and Evaluation of Serum Cytokines. A Pilot Study

2010

Ten free-living elderly were administered with a synbiotic [fermented milk containing Lactobacillus rhamnosus Gorbach and Goldin (LGG)] and oligofructose as a prebiotic for one month. Serum cytokines were evaluated before (T(0)) and after (T(1)) synbiotic administration. At T(0), values of Interleukin (IL)-12, IL-6, IL-10, IL-1beta and Tumor Necrosis Factor (TNF)-alpha were lower than normal controls, with the exception of IL-8, thus confirming previous results on the impairment of both innate and adaptive responses in elderly. At T(1), the synbiotic was able to significantly increase, depressed values of IL-1, IL-6 and IL-8 with a trend to a modest increase for the restant cytokines. In co…

Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activa…

2020

Rationale: Loss of histone macroH2A1 induces appearance of cancer stem cells (CSCs)-like cells in hepatocellular carcinoma (HCC). How CSCs interact with the tumor microenvironment and the adaptive immune system is unclear. Methods: We screened aggressive human HCC for macroH2A1 and CD44 CSC marker expression. We also knocked down (KD) macroH2A1 in HCC cells, and performed integrated transcriptomic and secretomic analyses. Results: Human HCC showed low macroH2A1 and high CD44 expression compared to control tissues. MacroH2A1 KD CSC-like cells transferred paracrinally their chemoresistant properties to parental HCC cells. MacroH2A1 KD conditioned media transcriptionally reprogrammed parental …

Angiotensin-(1-7) attenuates endothelial cell senescence via klotho and Nrf2 activation

2018

Age is not just a number – senescence affects how fish populations respond to different fishing regimes

2021

Abstract The presence of senescence in natural populations remains an unsolved problem in biology. Described as an age-dependent increase in natural mortality (known as actuarial senescence) and an age-dependent decrease in fecundity (known as reproductive senescence), the role of senescence in nature is still poorly understood. Based on empirical estimates of reproductive and actuarial senescence, we explored how senescence affects the population dynamics of Coregonus albula, a small, schooling salmonid fish. Using an empirically-based eco-evolutionary model, we investigated how the presence or absence of senescence affects how the fish population responds to pristine, intensive harvest, a…

Study of the combined effects of CDK1 inhibitors and senolytic drugs for the clearance of aneuploid-senescent cells

2022

Despite the progresses in discovering new therapeutic drugs and treatments, cancer is still one of the main causes of death. The biggest part of available treatments, moreover, is not always effective against tumour spread and it also has negative effects on the healthy tissues of the individual. For this reason, it is extremely relevant to find new strategies to avoid side effects during the anti-cancer therapies. Aneuploidy, an aberrant number of chromosomes in the cell, is a typical condition of cancer cells caused mainly by segregation errors and chromosomal instability (CIN). CIN is a process by which higher rate of chromosome segregation defects occurs by different mechanisms (chromos…