Cell biology and carcinogenesis in older people

2017 ◽  
pp. 691-698
Author(s):  
Tamas Fülöp ◽  
Vladimir N. Anisimov ◽  
Francis Rodier ◽  
Martine Extermann
Keyword(s):  
Risk Factor ◽  
Older People ◽  
Cellular Senescence ◽  
Cell Biology ◽  
Cellular Level ◽  
Pharmacological Interventions ◽  
Genetic Manipulations ◽  
Cellular Changes ◽  
Prevention And Treatment ◽  
Inflammatory Milieu

The most important risk factor for cancer is age and many age-associated molecular and cellular changes explain this relationship. The most important aspect of this relationship is the passage of time, which enables the multihit mutation process, resulting in the development of clinical cancer and contributing to the altered physiological environment that allows the full manifestation of these molecular mutations. At the cellular level, the double-edged sword process of cellular senescence will substantially contribute by creating an inflammatory milieu that supports increased tumorigenesis. Genomic instability that is closely related to cellular senescence, as well as epigenetic changes, will also play an important role. Nevertheless, there are strategies to decrease the lifelong increase of cancer incidence via nutrition, exercise, genetic manipulations, and pharmacological interventions. The discovery of biomarkers in the perspective of personalized medicine will also be a major breakthrough to improve cancer prevention and treatment in older people.

scholarly journals From the Infection to the Immunotherapy in Cervical Cancer: Can We Stop the Natural Course of the Disease?

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 597
Author(s):  
Daniela Luvero ◽  
Salvatore Lopez ◽  
Giorgio Bogani ◽  
Francesco Raspagliesi ◽  
Roberto Angioli
Keyword(s):  
Cervical Cancer ◽  
Radiation Therapy ◽  
Risk Factor ◽  
Hpv Vaccine ◽  
Global Market ◽  
Cancer Death ◽  
Prevention Measures ◽  
Primary And Secondary Prevention ◽  
The World ◽  
Prevention And Treatment

Cervical cancer (CC) is the second leading cause of cancer death in women aged 20–39 years. Persistent infection with oncogenic types of human papillomavirus (HPV) represents the most important risk factor for the development of cervical cancer. Three HPVs vaccines are currently on the global market: bivalent, quadrivalent, and nonavalent. The nonavalent vaccine provides protection against almost 90% of HPV-related CC. Despite availability of primary and secondary prevention measures, CC persists as one of the most common cancers among women around the world. Although CC is a largely preventable disease, management of persistent or recurrent CC no longer amenable to control with surgery or radiation therapy has not improved significantly with the progress of modern chemotherapy and disseminated carcinoma of the cervix remains a discouraging clinical entity with a 1-year survival rate between 10% and 15%. Over the last few years, there has been increasing interest in immunotherapy as a strategy to fight tumors. This article focuses on recent discoveries about the HPV vaccine and immunotherapies in the prevention and treatment of CC, highlighting the future view.

scholarly journals Respiratory Muscle Weakness as a Risk Factor for Pneumonia in Older People

Gerontology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Tatsuma Okazaki ◽  
Yoshimi Suzukamo ◽  
Midori Miyatake ◽  
Riyo Komatsu ◽  
Masahiro Yaekashiwa ◽  
...  
Keyword(s):  
Risk Factor ◽  
Muscle Strength ◽  
Older People ◽  
Serum Albumin ◽  
Muscle Mass ◽  
Muscle Weakness ◽  
Fat Mass ◽  
Respiratory Muscle ◽  
Respiratory Muscle Strength ◽  
Respiratory Muscle Weakness

Introduction: The respiratory muscle strength regulates the effectiveness of coughing, which clears the airways and protects people from pneumonia. Sarcopenia is an aging-related loss of muscle mass and function, the worsening of which is associated with malnutrition. The loss of respiratory and swallowing muscle strength occurs with aging, but its effect on pneumonia is unclear. This study aimed to determine the risks of respiratory muscle weakness on the onset and relapse of pneumonia in older people in conjunction with other muscle-related factors such as malnutrition. Methods: We conducted a longitudinal study with 47 pneumonia inpatients and 35 non-pneumonia controls aged 70 years and older. We evaluated the strength of respiratory and swallowing muscles, muscle mass, and malnutrition (assessed by serum albumin levels and somatic fat) during admission and confirmed pneumonia relapse within 6 months. The maximal inspiratory and expiratory pressures determined the respiratory muscle strength. Swallowing muscle strength was evaluated by tongue pressure. Bioelectrical impedance analysis was used to evaluate the muscle and fat mass. Results: The respiratory muscle strength, body trunk muscle mass, serum albumin level, somatic fat mass, and tongue pressure were significantly lower in pneumonia patients than in controls. Risk factors for the onset of pneumonia were low inspiratory respiratory muscle strength (odds ratio [OR], 6.85; 95% confidence interval [CI], 1.56–30.11), low body trunk muscle mass divided by height2 (OR, 6.86; 95% CI, 1.49–31.65), and low serum albumin level (OR, 5.46; 95% CI, 1.51–19.79). For the relapse of pneumonia, low somatic fat mass divided by height2 was a risk factor (OR, 20.10; 95% CI, 2.10–192.42). Discussion/Conclusions: Respiratory muscle weakness, lower body trunk muscle mass, and malnutrition were risk factors for the onset of pneumonia in older people. For the relapse of pneumonia, malnutrition was a risk factor.

scholarly journals The Cellular Senescence Stress Response in Post-Mitotic Brain Cells: Cell Survival at the Expense of Tissue Degeneration

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 229
Author(s):  
Eric Sah ◽  
Sudarshan Krishnamurthy ◽  
Mohamed Y. Ahmidouch ◽  
Gregory J. Gillispie ◽  
Carol Milligan ◽  
...  
Keyword(s):  
Stress Response ◽  
Cell Fate ◽  
Cellular Senescence ◽  
Cell Biology ◽  
Brain Aging ◽  
Complex Stress ◽  
Brain Cell ◽  
Tissue Degeneration ◽  
Cellular Dna

In 1960, Rita Levi-Montalcini and Barbara Booker made an observation that transformed neuroscience: as neurons mature, they become apoptosis resistant. The following year Leonard Hayflick and Paul Moorhead described a stable replicative arrest of cells in vitro, termed “senescence”. For nearly 60 years, the cell biology fields of neuroscience and senescence ran in parallel, each separately defining phenotypes and uncovering molecular mediators to explain the 1960s observations of their founding mothers and fathers, respectively. During this time neuroscientists have consistently observed the remarkable ability of neurons to survive. Despite residing in environments of chronic inflammation and degeneration, as occurs in numerous neurodegenerative diseases, often times the neurons with highest levels of pathology resist death. Similarly, cellular senescence (hereon referred to simply as “senescence”) now is recognized as a complex stress response that culminates with a change in cell fate. Instead of reacting to cellular/DNA damage by proliferation or apoptosis, senescent cells survive in a stable cell cycle arrest. Senescent cells simultaneously contribute to chronic tissue degeneration by secreting deleterious molecules that negatively impact surrounding cells. These fields have finally collided. Neuroscientists have begun applying concepts of senescence to the brain, including post-mitotic cells. This initially presented conceptual challenges to senescence cell biologists. Nonetheless, efforts to understand senescence in the context of brain aging and neurodegenerative disease and injury emerged and are advancing the field. The present review uses pre-defined criteria to evaluate evidence for post-mitotic brain cell senescence. A closer interaction between neuro and senescent cell biologists has potential to advance both disciplines and explain fundamental questions that have plagued their fields for decades.

scholarly journals Reconstruction ofmreBExpression in Staphylococcus aureus via a Collection of New Integrative Plasmids

2014 ◽  
Vol 80 (13) ◽  
pp. 3868-3878 ◽  
Author(s):  
Ana Yepes ◽  
Gudrun Koch ◽  
Andrea Waldvogel ◽  
Juan-Carlos Garcia-Betancur ◽  
Daniel Lopez
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Biology ◽  
Genetic Manipulation ◽  
Protein Localization ◽  
Antibiotic Resistance Genes ◽  
Wall Material ◽  
Content Type ◽  
Genetic Manipulations ◽  
Discrete Structures

ABSTRACTProtein localization has been traditionally explored in unicellular organisms, whose ease of genetic manipulation facilitates molecular characterization. The two rod-shaped bacterial modelsEscherichia coliandBacillus subtilishave been prominently used for this purpose and have displaced other bacteria whose challenges for genetic manipulation have complicated any study of cell biology. Among these bacteria is the spherical pathogenic bacteriumStaphylococcus aureus. In this report, we present a new molecular toolbox that facilitates gene deletion in staphylococci in a 1-step recombination process and additional vectors that facilitate the insertion of diverse reporter fusions into newly identified neutral loci of theS. aureuschromosome. Insertion of the reporters does not add any antibiotic resistance genes to the chromosomes of the resultant strains, thereby making them amenable for further genetic manipulations. We used this toolbox to reconstitute the expression ofmreBinS. aureus, a gene that encodes an actin-like cytoskeletal protein which is absent in coccal cells and is presumably lost during the course of speciation. We observed that inS. aureus, MreB is organized in discrete structures in association with the membrane, leading to an unusual redistribution of the cell wall material. The production of MreB also caused cell enlargement, but it did not revert staphylococcal shape. We present interactions of MreB with key staphylococcal cell wall-related proteins. This work facilitates the useS. aureusas a model system in exploring diverse aspects of cellular microbiology.

scholarly journals The Basolateral Polarity Module Promotes Slit Diaphragm Formation in Drosophila Nephrocytes, a Model of Vertebrate Podocytes

2021 ◽  
pp. ASN.2020071050
Author(s):  
Michael Mysh ◽  
John S. Poulton
Keyword(s):  
Nephrotic Syndrome ◽  
Protein Trafficking ◽  
Cell Biology ◽  
Genetic Interaction ◽  
Intercellular Junctions ◽  
Protein Distribution ◽  
Genetic Manipulations ◽  
Apicobasal Polarity ◽  
Apical Polarity ◽  
Polarity Proteins

BackgroundPodocyte slit diaphragms (SDs) are intercellular junctions that function as size-selective filters, excluding most proteins from urine. Abnormalities in SDs cause proteinuria and nephrotic syndrome. Podocytes exhibit apicobasal polarity, which can affect fundamental aspects of cell biology, including morphology, intercellular junction formation, and asymmetric protein distribution along the plasma membrane. Apical polarity protein mutations cause nephrotic syndrome, and data suggest apical polarity proteins regulate SD formation. However, there is no evidence that basolateral polarity proteins regulate SDs. Thus, the role of apicobasal polarity in podocytes remains unclear.MethodsGenetic manipulations and transgenic reporters determined the effects of disrupting apicobasal polarity proteins in Drosophila nephrocytes, which have SDs similar to those of mammalian podocytes. Confocal and electron microscopy were used to characterize SD integrity after loss of basolateral polarity proteins, and genetic-interaction studies illuminated relationships among apicobasal polarity proteins.ResultsThe study identified four novel regulators of nephrocyte SDs: Dlg, Lgl, Scrib, and Par-1. These proteins comprise the basolateral polarity module and its effector kinase. The data suggest these proteins work together, with apical polarity proteins, to regulate SDs by promoting normal endocytosis and trafficking of SD proteins.ConclusionsGiven the recognized importance of apical polarity proteins and SD protein trafficking in podocytopathies, the findings connecting basolateral polarity proteins to these processes significantly advance our understanding of SD regulation.

scholarly journals What happens to anxiety disorders in later life?

2002 ◽  
Vol 24 (suppl 1) ◽  
pp. 74-80 ◽  
Author(s):  
Gerard JA Byrne
Keyword(s):  
Anxiety Disorders ◽  
Older People ◽  
Older Patients ◽  
Depressive Disorders ◽  
Late Onset ◽  
Reliability And Validity ◽  
Later Life ◽  
Pharmacological Interventions ◽  
Measuring Change ◽  
Pathological Anxiety

Anxiety disorders decline in prevalence with advancing age but remain more common than depressive disorders. They are often of late-onset and there is frequent comorbidity with depressive disorders and physical illness. While anxiety disorders in older people are likely to respond to the same non-pharmacological interventions that have been shown to work in younger people, there is currently little formal evidence of this. Although there is some evidence that the non-benzodiazepine anxiolytic medication, buspirone, is effective against late life anxiety symptoms, clinical trials in older people with rigorously diagnosed anxiety disorders are needed. An anxiety scale with demonstrated reliability and validity in older people is needed for screening for pathological anxiety and for measuring change in older patients undergoing treatment for anxiety disorders.

Abstract 18111: Flecainide Exerts its Antiarrhythmic Action in CPVT Through Blockade of Neuronal Na+ channel-mediated Arrhythmogenic Diastolic Ca2+ Release

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Przemyslaw Radwanski ◽  
Hsiang-Ting Ho ◽  
Björn Knollmann ◽  
Andriy Belevych ◽  
Sándor Györke
Keyword(s):  
Ventricular Myocytes ◽  
Ryanodine Receptors ◽  
Cellular Level ◽  
Antiarrhythmic Effect ◽  
Na Channel ◽  
Antiarrhythmic Action ◽  
Pharmacological Interventions ◽  
Cellular Excitability

Background: Flecaininde is an effective antiarrhythmic in management of CPVT. Its antiarrhythmic action has been attributed to direct effect on RyR2 and reduced cellular excitability through the inhibition of cardiac-type Na + channels. Recently we demonstrated that neuronal Na + channels (nNa v s) colocalize with the ryanodine receptors (RyR2) Ca 2+ release channels on the sarcoplasmic reticulum. Here we explore a novel mechanism that may contribute to the antiarrhythmic effect of flecainide, mainly uncoupling of aberrant Na + /Ca 2+ signaling through nNa v inhibition. Methods: To study the effects of flecainide on Ca 2+ signaling we used a murine model of cardiac calsequestrin-associated CPVT. We performed confocal microscopy in intact isolated ventricular myocytes to assess Ca 2+ handling and recorded late Na + current (I Na ) during various pharmacological interventions. Surface electrocardiograms were performed during catecholamine challenge to monitor arrhythmic activity in vivo . Results: During catecholamine stimulation with isoproterenol (Iso; 100 nM) disruption of the cross-talk between nNa v s and RyR2 by nNa v blockade with 100nM tetrodotoxin (TTX) and riluzole (10μM) as well as flecainide (2.5μM) reduced Iso-promoted late I Na and DCR in isolated intact CPVT cardiomyocytes. To further examine the role of nNa v -mediated late I Na in genesis of DCR we augmented nNa v channel activity with β-Pompilidotoxin (β-PMTX, 40μM). Effects of β-PMTX in CPVT cardiomyocytes were reversed by nNa v blockade with TTX and riluzole as well as flecainide. This reduction in late I Na and DCR frequency with riluzole and flecainide in the presence of β-PMTX on cellular level translated to decreased ventricular arrhythmias in CPVT mice. Conclusion: These data suggest that disruption of nNa v -mediated late I Na can prevent arrhythmogenic DCR in CPVT. Importantly, the antiarrhythmic effects of flecainide can be attributed, at least in part, to its nNa v blocking properties.

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