Important aging mechanism revealed
African killifish as model organism
Nothobranchius furzeri, the African killifish, is the perfect model organism for research into aging processes because of its short lifespan, apparent signs of aging and a sequenced genome. Thus, researchers from the University of Veterinary Medicine Vienna and the Medical University of Vienna were able to show that histone deacetylases, which are important for cell cycle regulation are produced less in aging fish. In parallel, the team confirmed this aging mechanism in mice. The identification of epigenetic and thus, reversible changes could be a loophole to develop active compounds antagonising the aging process.
An important aging mechanism, a permanent reduction of histone deacetylases, was recently identified in the african Killifish, N. furzeri.
The Austrian Northo Project
People have long been dealing with questions about the mechanisms that make our body cells age and how to counteract these mechanisms. Due to their function in cell cycle regulation, histone deacetylases, HDACs, are considered to play an essential role in the cellular aging process and in the development of neurodegenerative diseases. A research team around Sabine Lagger from the Unit of Pathology of Laboratory Animals of the University of Veterinary Medicine Vienna, in collaboration with Gordin Zupkovitz and Oliver Pusch from the Medical University of Vienna analysed these connections and confirmed a clear mechanism in the extremely short-lived killifish from the onset of embryogenesis until the last phase of life.
Cell cycle inhibitor replaces positive regulation enzymes in the aging process
The short-lived turquoise killifish, Nothobranchius furzeri, has been an emerging model organism in aging research for several years. Since 2014, the Medical University of Vienna has been conducting research into this species in its Killifish Facility, which constitutes the only one of its kind in Austria. The species’ short lifespan of about four months is not the only argument, as N. furzeri also shows clear signs of aging such as dementia and cancerous lesions. Additionally a fully annotated genome is available. This “comprehensive package” enables analyses of cellular aging processes, virtually in fast forward motion.
“We analysed the expression of histone deacetylases because these proteins are often related to aging processes,” explained Lagger. HDACs are involved in mechanisms how the genome is transcribed in a particular moment. The DNA does not exist freely in cells but is wrapped around complex protein structures. It is, in a way, strategically packed. “Some parts can be modified by certain chemical modifications so that specific genes can be transcribed or not. Which parts are accessible or not depends on external factors, such as environmental conditions, stress, or endogenous processes, such as aging,” said the lead author.
The analyses done by the team showed that the expression levels of HDACs was constantly downregulated in aging killifish. This decrease of available HDACs resulted in the increasing production of the cell cycle inhibitor protein p21. The researchers also confirmed this dynamic in a mammalian animal model. “The HDAC-p21 connection was mirrored in the mouse. This even allows us to conclude that there is an evolutionarily conserved mechanism of cellular aging,” said Lagger.
Epigenetic background could open doors for an active compound strategy
Furthermore, the availability of HDACs and the connection with the aging process is interesting because it influences the epigenetic regulation of the cell cycle. “In contrast to genetic mutations in the DNA sequence, epigenetic changes are reversible. This could be an approach for the development of active compounds able to inhibit the described mechanism,” concludes Lagger.
Original publication
Other news from the department science
Most read news
More news from our other portals
Last viewed contents
Seeing a diagnosis: How an eye test could aid Alzheimer's detection
C-mo Medical Solutions raises €4.1 million aiming to transform cough monitoring
New technique for testing drugs to treat cystic fibrosis and epilepsy
Neuronal Parkinson inclusions are different than expected - Study raises new questions about the etiology of Parkinson’s disease
Analytik Jena Sells Site in Eisfeld - New investor acquiring entire Optics business unit as well as component production for analytical technology
Toxic agents behind Parkinson's disease seen at work for the first time - First look at how toxic protein clusters disrupt the membranes of healthy brain cells.
Ocean Optics Employee Wins Global Technology Award - Nelson Chandler takes £20K top prize from multi-national technology company
Measuring the magnetism of antimatter - Researchers measure antiprotons more accurately than ever before
KRÜSS is one of the innovation leaders in 2018 - TOP 100 competition success
COVID-19 : Measuring viral RNA to predict which patients will die - A statistical model uses a blood biomarker of SARS-CoV-2 to identify infected patients who are most at risk of dying of COVID-19
