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Radhakrishnan Vishnubalaji, Muthurangan Manikandan, Abdullah Aldahmash, Abdullah AlJarbou, Mohamad Habous, Dulaim Alhajeri, Raed Almannie, Musaad Alfayez, Nehad M Alajez, Saleh Binsaleh
BACKGROUND: Stem cell-based therapies have recently been explored in the field of erectile dysfunction (ED). However, the cellular and molecular phenotype of adipose derived stem cells (ADSCs) stromal vascular fraction (SVF) from ED patients remains largely unknown. Herein we compared the global gene expression profile in the SVF from ED patients and healthy individuals and identified altered signaling pathways between the two groups. METHODS: Samples (2-5g) of abdominal adipose tissue from ED patients (n=6) and healthy individual controls (n=3) undergoing elective cosmetic liposuction were collected...
October 17, 2018: Bioscience Reports
Abbas Ishaq, Damien Dufour, Kerry Cameron, Thomas von Zglinicki, Gabriele Saretzki
Dietary restriction (DR) is thought to exert its beneficial effects on healthspan at least partially by a senolytic and senostatic action, i.e. by reducing frequencies of cells with markers of DNA damage and senescence in multiple tissues. Due to its importance in metabolic and inflammation regulation, fat is a prime tissue for health span determination as well as a prime target for DR. We aimed to determine here whether the beneficial effects of DR would be retained over a subsequent period of ad libitum (AL) feeding...
October 9, 2018: Experimental Gerontology
Raheleh Farahzadi, Ezzatollah Fathi, Seyed Alireza Mesbah-Namin, Nosratollah Zarghami
The identification of factors that reduce the senescent tendency of the mesenchymal stem cells (MSCs) upon expansion has great potential for cellular therapies in regenerative medicine. Previous studies have shown the aging protective effect of L-carnitine (LC). On the other hand, reduction in proliferation potential and age-dependent decline in number and functions of MSCs were accompanied by telomere shortening, reduction in telomerase activity and epigenetic changes. The aim of this study was to evaluate the effects of LC on aging of MSCs through telomerase activity assessment and the investigation of methylation status of the hTERT gene promoter...
October 2018: Tissue & Cell
Durgesh Kumar, Sanket Kumar Pandya, Salil Varshney, Kripa Shankar, Sujith Rajan, Ankita Srivastava, Abhishek Gupta, Sanchita Gupta, Achchhe Lal Vishwakarma, Amit Misra, Anil N Gaikwad
BACKGROUND/OBJECTIVES: Chronic low-grade inflammation/meta-inflammation in adipose tissue leads to obesity-associated metabolic complications. Despite growing understanding, the roles of immune cell subsets, their interrelationship, and chronological events leading to progression of obesity-associated insulin resistance (IR) remains unclear. METHODS: We carried out temporal immunometabolic profiling of adipose tissue from C57BL/6 mice fed a high-fat diet (HFD) for 4, 8, 12, 16, and 20 weeks...
October 9, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Matthew J Yousefzadeh, Yi Zhu, Sara J McGowan, Luise Angelini, Heike Fuhrmann-Stroissnigg, Ming Xu, Yuan Yuan Ling, Kendra I Melos, Tamar Pirtskhalava, Christina L Inman, Collin McGuckian, Erin A Wade, Jonathon I Kato, Diego Grassi, Mark Wentworth, Christin E Burd, Edgar A Arriaga, Warren L Ladiges, Tamara Tchkonia, James L Kirkland, Paul D Robbins, Laura J Niedernhofer
BACKGROUND: Senescence is a tumor suppressor mechanism activated in stressed cells to prevent replication of damaged DNA. Senescent cells have been demonstrated to play a causal role in driving aging and age-related diseases using genetic and pharmacologic approaches. We previously demonstrated that the combination of dasatinib and the flavonoid quercetin is a potent senolytic improving numerous age-related conditions including frailty, osteoporosis and cardiovascular disease. The goal of this study was to identify flavonoids with more potent senolytic activity...
October 2018: EBioMedicine
Nhat Chau Truong, Khanh Hong-Thien Bui, Phuc Van Pham
INTRODUCTION: Since the 1980s, adipose-derived stem cells (ASCs) have become a powerful and potential source for stem cell-based therapy, regenerative medicine, and even drug delivery in cancer treatment. The development of off-the-shelf mesenchymal stem cells (MSCs), including ASCs, has rapidly advanced in recent years with several clinical trials and approved products. In this technology, ASCs should be expanded long term in order to harvest higher cell number. In this study, senescence of ASCs after long-term expansion was evaluated...
September 22, 2018: Advances in Experimental Medicine and Biology
Y Meng, A Eirin, X-Y Zhu, H Tang, L J Hickson, A Lerman, A J van Wijnen, L O Lerman
Mesenchymal stem cells (MSCs) constitute an important repair system, but may be impaired by exposure to cardiovascular risk factors. Consequently, adipose tissue-derived MSCs from pigs with the metabolic syndrome (MetS) show decreased vitality. A growing number of microRNAs (miRNAs) are recognized as key modulators of senescence, but their role in regulating senescence in MSC in MetS is unclear. We tested the hypothesis that MetS upregulates in MSC expression of miRNAs that can serve as post-transcriptional regulators of senescence-associated (SA) genes...
October 2018: Cell Transplantation
Roberta Fajka-Boja, Annamária Marton, Anna Tóth, Péter Blazsó, Vilmos Tubak, Balázs Bálint, István Nagy, Zoltán Hegedűs, Csaba Vizler, Robert L Katona
BACKGROUND: Adipose-tissue stem cells (ASCs) are subject of intensive research since their successful use in regenerative therapy. The drawback of ASCs is that they may serve as stroma for cancer cells and assist tumor progression. It is disquieting that ASCs frequently undergo genetic and epigenetic changes during their in vitro propagation. In this study, we describe the polyploidization of murine ASCs and the accompanying phenotypical, gene expressional and functional changes under long term culturing...
September 5, 2018: BMC Cancer
Jelena Krstic, Isabel Reinisch, Michael Schupp, Tim J Schulz, Andreas Prokesch
As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue- and cell-specific actions of p53 and its downstream signaling pathways...
September 4, 2018: International Journal of Molecular Sciences
Antonia Graja, Sabrina Gohlke, Tim J Schulz
Brown adipose tissue aging and the concomitant loss of thermogenic capacity have been linked to an inability to maintain normal energy homeostasis in late life. Similarly, the ability of white fat to convert into brite/beige adipose tissue declines. This may ultimately exacerbate the progression of age-related metabolic pathologies, such as insulin resistance and obesity. The depletion of all types of brown adipocytes during aging is well-established and has been described in rodent models as well as humans...
August 24, 2018: Handbook of Experimental Pharmacology
Zhuohao Liu, Leigang Jin, Jin-Kui Yang, Baile Wang, Kelvin Kl Wu, Philip Hallenborg, Aimin Xu, Kenneth Ky Cheng
Profound loss and senescence of adipose tissues are hallmarks of advanced age, but the underlying cause and their metabolic consequences remain obscure. Proper function of MDM2-p53 axis is known to prevent tumorigenesis and several metabolic diseases, yet its role in regulation of adipose tissue ageing is still poorly understood. Here, we show that the proximal p53 inhibitor murine double minute 2 (MDM2) is markedly downregulated in subcutaneous white and brown adipose tissues of mice during ageing. Genetic disruption of MDM2 in adipocytes triggers canonical p53-mediated apoptotic and senescent programs, leading to age-dependent lipodystrophy and its associated metabolic disorders including type 2 diabetes, non-alcoholic fatty liver disease, hyperlipidemia and energy imbalance...
August 21, 2018: Diabetes
Zhengjie Wang, Xiaolong Xu, Yi Liu, Yongheng Gao, Fei Kang, Baohua Liu, Jing Wang
Brown adipose tissue (BAT) is an important energy metabolic organ that is highly implicated in obesity, type 2 diabetes, and atherosclerosis. Aging is one of the most important determinants of BAT activity. In this study, we used 18 F-FDG PET/CT imaging to assess BAT aging in Lmna-/- mice. The maximum standardized uptake value (SUVMax ) of the BAT was measured, and the target/nontarget (T/NT) values of BAT were calculated. The transcription and the protein expression levels of the uncoupling protein 1 (UCP1), beta3-adrenergic receptor ( β 3-AR), and the PR domain-containing 16 (PRDM16) were measured by quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting or immunohistochemical analysis...
2018: Contrast Media & Molecular Imaging
Tomoya Yamada, Mituru Kamiya, Mikito Higuchi, Naoto Nakanishi
Obesity is associated with the chronic inflammation and senescence of adipose tissues. Macrophage is a key mediator of chronic inflammation that infiltrates obese adipose tissue and stimulates metabolic disorders. However, the fat depot-specific differences of macrophage infiltration and senescence, especially the influence on intramuscular adipose tissue, have remained unclear. We investigated the fat depot-specific differences of macrophage infiltration and senescence in obese bovine adipose tissue from three different anatomical sites (subcutaneous, intramuscular and visceral)...
August 15, 2018: Journal of Veterinary Medical Science
Barbara Bellei, Emilia Migliano, Marinella Tedesco, Silvia Caputo, Federica Papaccio, Gianluca Lopez, Mauro Picardo
BACKGROUND: Adipose tissue-derived stem cells are considered to be a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using adipose tissue or purified stem cells, intercellular molecule exchange by the adipose tissue complex, a vast array of bioactive secretory factors, demonstrated beneficial effects by reducing tissue damage and stimulation of endogenous repair. However, for therapeutic purposes, the use of secretome derivatives, such as full conditioned media or purified exosomes generated in vitro, may present considerable disadvantages for cell manufacturing, storage, product safety, and their potential as a ready-to-go therapeutic product...
August 9, 2018: Stem Cell Research & Therapy
Wenyan Fu, Yang Liu, Christina Sun, Hang Yin
Aging of white adipose tissue (WAT) is associated with reduced insulin sensitivity, which contributes to whole-body glucose intolerance. WAT aging in mice impairs cold-induced beige adipocyte recruitment (beiging), which has been attributed to the senescence of adipose progenitor cells. Tumor suppressor p53 has also been implicated in WAT aging. However, whether p53-related cellular aging in mature white adipocytes is causative of age-impaired WAT beiging remains unknown. It is also unclear whether transient p53 inhibition can rescue WAT beiging...
July 27, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ming Xu, Tamar Pirtskhalava, Joshua N Farr, Bettina M Weigand, Allyson K Palmer, Megan M Weivoda, Christina L Inman, Mikolaj B Ogrodnik, Christine M Hachfeld, Daniel G Fraser, Jennifer L Onken, Kurt O Johnson, Grace C Verzosa, Larissa G P Langhi, Moritz Weigl, Nino Giorgadze, Nathan K LeBrasseur, Jordan D Miller, Diana Jurk, Ravinder J Singh, David B Allison, Keisuke Ejima, Gene B Hubbard, Yuji Ikeno, Hajrunisa Cubro, Vesna D Garovic, Xiaonan Hou, S John Weroha, Paul D Robbins, Laura J Niedernhofer, Sundeep Khosla, Tamara Tchkonia, James L Kirkland
Physical function declines in old age, portending disability, increased health expenditures, and mortality. Cellular senescence, leading to tissue dysfunction, may contribute to these consequences of aging, but whether senescence can directly drive age-related pathology and be therapeutically targeted is still unclear. Here we demonstrate that transplanting relatively small numbers of senescent cells into young mice is sufficient to cause persistent physical dysfunction, as well as to spread cellular senescence to host tissues...
August 2018: Nature Medicine
Maria I Guillén, Julia Platas, María D Pérez Del Caz, Vicente Mirabet, Maria J Alcaraz
The inflammatory process is an essential phenomenon in the induction of immune responses. Monocytes are key effector cells during the inflammatory process. A wide range of evidence indicates that mesenchymal stem cells from adipose tissue (ASC) are endowed with immunomodulatory capacity. However, the interaction between ASC and monocytes in the innate immune response is not well understood. The aim of this work was to investigate the possible paracrine anti-inflammatory effects of ASC in human monocytes. Monocytes were isolated from buffy coats and ASC from fat of non-obese patients...
2018: Frontiers in Physiology
Sergio Perez-Diaz, Maria P Garcia-Sobreviela, Yolanda Gonzalez-Irazabal, Beatriz Garcia-Rodriguez, Silvia Espina, Izaskun Arenaz, Jose M Arbones-Mainar
Adipose tissue (AT) expands under obesogenic conditions. Yet, when the growth exceeds a certain limit, AT becomes dysfunctional and surplus lipids start depositing ectopically. Polymerase I and transcription release factor (PTRF) has been proposed as a mechanism leading to a dysfunctional AT by decreasing the adipogenic potential of human adipocyte precursors. However, whether or not PTRF can be secreted by the adipocytes into the bloodstream is not yet known. For this work, PTRF presence was investigated in plasma...
June 4, 2018: Journal of Physiology and Biochemistry
Marianna Kunrath-Lima, Marcelo Coutinho de Miranda, Andrea da Fonseca Ferreira, Camila Cristina Fraga Faraco, Mariane Izabella Abreu de Melo, Alfredo Miranda Goes, Michele Angela Rodrigues, Jerusa Araújo Quintão Arantes Faria, Dawidson Assis Gomes
Ca2+ is an important second messenger, and it is involved in many cellular processes such as cell death and proliferation. The rise in intracellular Ca2+ levels can be due to the generation of inositol 1,4,5-trisphosphate (InsP3 ), which is a product of phosphatidylinositol 4,5-bisphosphate (PIP2 ) hydrolysis by phospholipases C (PLCs), that leads to Ca2+ release from endoplasmic reticulum by InsP3 receptors (InsP3 R). Ca2+ signaling patterns can vary in different regions of the cell and increases in nuclear Ca2+ levels have specific biological effects that differ from those of Ca2+ increase in the cytoplasm...
September 2018: Cellular Signalling
Sean Delaney, Russell W H Kridel
Background: The midface is particularly prone to the senescent changes of soft tissue ptosis and volume loss, which in individuals with aging or low adiposity can manifest as submalar hollowing. Facelift alone in those with submalar hollowing inadequately addresses the volume loss and may result in a gaunt appearance postoperatively. Submalar implant augmentation is a powerful tool for permanent midface volume restoration for a more youthful and natural contour, as opposed to soft tissue fillers that diminish over time...
May 28, 2018: Aesthetic Surgery Journal
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