Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
Cohesin down-regulation drives hematopoietic stem cell aging

Cohesin down-regulation drives hematopoietic stem cell aging

Cohesin down-regulation drives hematopoietic stem cell aging
InflammAging affects hematopoietic stem cells (HSCs) through impairing their function and self-renewal by constant activation of cohesin-mediated inflammatory signals. This leads to the selection of HSCs with low expression of cohesin, increased self-renewal, and unbalanced differentiation into inflammatory/myeloid cells. In turn, InflammAging is further increased and drives disease development in aging. Credit: Graphic: Kerstin Wagner / FLI; Source: www.pixabay.de

Aging is characterized by increases in inflammation and decreases in stem cell function. The relationship between these processes remains incompletely understood. Researchers of the Leibniz Institute on Aging (FLI) in Jena, Germany, identified a new role of the protein cohesin in mediating inflammatory signaling in hematopoietic stem cells (HSCs). Cohesin is required for gene regulation during normal differentiation, but chronic inflammation in aging impairs the function and self-renewal of HSCs by constant activation of cohesin-mediated inflammatory signals. HSC with reduced cohesin, increased self-renewal and skewed differentiation are selected, resembling the hallmarks of hematopoietic aging.

Jena. As the human body ages, inflammation increases and this accelerates the development of aging-associated diseases, a process called “InflammAging.” This process also affects the hematopoietic system in a way that inflammation instructs the stem cells of the system (hematopoietic stem cells, HSCs) to exhibit abnormal self-renewal and unbalanced differentiation into inflammatory/myeloid cells, which in turn leads to a further acceleration of InflammAging. The drivers of stem cell aging are still incompletely understood. Gaining mechanistic insights into this process holds the promise to develop therapies to improve health during aging.

Researchers of the Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) in Jena, Germany, have now found that the cohesin complex – a DNA clamp-holder – plays an important role in HSC response to inflammation and as such appears to drive key features of hematopoietic aging and InflammAging. The results are now published in the Journal of Experimental Medicine.

Hematopoietic system during aging and inflammation

A well working hematopoietic system is based on a balanced potential of the HSCs to differentiate into all important cell types of the blood system and to renew themselves as stem cells (self-renewal). During aging and increasing, chronic inflammation, the balance of the hematopoietic system is lost. HCSs show impaired repopulation capacity and skewed differentiation: This means they are more likely to differentiate into inflammatory/myeloid cells than into lymphoid cells.

The transcription factor NF-κB controls many genes involved in inflammation. The pathway is activated in many inflammatory diseases. During aging, an increase in NF-κB signaling has been identified in HSCs. However, the functional consequences of enhanced NF-kB signaling on hematopoietic stem cells aging have not been worked out.

Cohesin as critical mediator of NF-κB signaling

Researchers of the Leibniz Institute on Aging (FLI) in Jena and their collaborators investigated aging and inflammation processes and their effects on the hematopoietic system. “We knew that aging comes along with increased inflammation, but the consequences of chronic inflammation for hematopoietic stem cells and organism aging were incompletely understood,” Dr. Zhiyang Chen, postdoctoral researcher at FLI explains his motivation behind the study.

The current study increases our understanding and shows that cohesin mediates inflammatory signaling in HSCs and that this has functional consequences during aging and inflammatory processes. Cohesin turns out to be important for normal differentiation of HSCs, but during aging and inflammation the same regulatory loop limits the stem cell function, especially the self-renewal capacity of the HSCs. Old HSCs fail to down-regulate cohesin-mediated inflammatory signals that remain chronically activated during aging.

“This mechanism of constant inflammation exhausts the stem cell pool and pushes the stem cells into faulty differentiation into inflammatory cells,” summarizes Prof. K. Lenhard Rudolph, senior group leader at FLI. “In turn, these impairments increase the selection of abnormal stem cells with lower expression of cohesin that exhibit increases in self-renewal and mal-differentiation into inflammatory/myeloid cells – a hallmark feature of the hematopoietic system, which accelerates organism aging.” Interfering with this molecular loop of chronic inflammation in aging hematopoietic stem cells could help to slow down aging and the development of aging-associated diseases such as cancer, cardiovascular and neurodegenerative diseases that are driven by increases in inflammation.


Molecule that supports blood-cell production under dietary stress is identified


More information:
Zhiyang Chen et al. Cohesin-mediated NF-κB signaling limits hematopoietic stem cell self-renewal in aging and inflammation, The Journal of Experimental Medicine (2018). DOI: 10.1084/jem.20181505


Provided by
Leibniz Institute on Aging

Citation:
Cohesin down-regulation drives hematopoietic stem cell aging (2018, December 14)
retrieved 12 January 2019
from https://medicalxpress.com/news/2018-12-cohesin-down-regulation-hematopoietic-stem-cell.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

Tagged with:

About author

Related Articles