Loading...
Projects / Programmes source: ARIS

Impact of oxidative stress on length and structure of telomeres in children and adolescents with type 1 diabetes or hypercholesterolemia

Research activity

Code Science Field Subfield
3.05.00  Medical sciences  Human reproduction   

Code Science Field
B660  Biomedical sciences  Pediatrics 

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
Keywords
Telomere length, type 1 diabetes, hypercholesterolemia, oxidative stress, G-quadruplexes
Evaluation (rules)
source: COBISS
Researchers (25)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  23435  PhD Magdalena Avbelj Stefanija  Human reproduction  Researcher  2014 - 2017  177 
2.  13023  PhD Tadej Battelino  Medical sciences  Researcher  2014 - 2017  1,246 
3.  13409  PhD Nataša Bratina  Human reproduction  Researcher  2014 - 2017  433 
4.  24448  PhD Mirko Cevec  Biochemistry and molecular biology  Researcher  2016 - 2017  67 
5.  38333  Vanda Cucek    Technical associate  2016 - 2017 
6.  15657  PhD Maruša Debeljak  Oncology  Researcher  2014 - 2017  248 
7.  22251  Jurka Ferran    Technical associate  2014 - 2017 
8.  38332  Maja Ficko  Human reproduction  Technical associate  2016 - 2017  10 
9.  33868  PhD Urh Grošelj  Human reproduction  Researcher  2014 - 2017  485 
10.  28512  PhD Tinka Hovnik  Medical sciences  Researcher  2014 - 2017  107 
11.  34575  PhD Gašper Klančar  Oncology  Researcher  2014 - 2016  74 
12.  21358  PhD Primož Kotnik  Human reproduction  Researcher  2014 - 2017  247 
13.  32181  PhD Jernej Kovač  Medical sciences  Researcher  2014 - 2015  210 
14.  32112  PhD Martina Lenarčič Živković  Biochemistry and molecular biology  Researcher  2014 - 2017  61 
15.  29097  Brigita Mali    Technical associate  2014 - 2017 
16.  26462  PhD Simona Murko  Metabolic and hormonal disorders  Researcher  2014  64 
17.  10082  PhD Janez Plavec  Chemistry  Researcher  2014 - 2017  1,263 
18.  28022  PhD Peter Podbevšek  Chemistry  Researcher  2014 - 2017  119 
19.  14020  PhD Barbka Repič Lampret  Human reproduction  Researcher  2014 - 2017  162 
20.  36427  PhD Andraž Šmon  Metabolic and hormonal disorders  Junior researcher  2014 - 2017  41 
21.  37490  PhD Tine Tesovnik  Human reproduction  Junior researcher  2015 - 2017  65 
22.  20128  PhD Alenka Trampuš Bakija  Cardiovascular system  Researcher  2014 - 2017  128 
23.  20253  PhD Katarina Trebušak Podkrajšek  Human reproduction  Head  2014 - 2017  407 
24.  23267  Mirjana Zupančič  Human reproduction  Researcher  2014 - 2017  86 
25.  15440  PhD Mojca Žerjav Tanšek  Human reproduction  Researcher  2014 - 2017  318 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  21,092 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,757 
Abstract
Telomeres are DNA-protein complexes capping the end of eukaryotic chromosomes. Their role is to ensure genomic stability and prevent chromosomal breaks ultimately leading to apoptosis. Consequently, length, dynamics and structure of telomeres are extensively investigated in aging, cancer and complex disorders but their role is still not completely explained. Telomeres are considered to be an important biomarker, combining the effect of various factors, such as the total number of cell divisions and the cumulative exposure of cells to the oxidative and nitrosative stress. Telomere length (TL) is inversely correlated with oxidative stress, since the combination of prolonged exposure to reactive oxidative species (ROS) leads to increased rate of telomere ends deterioration. Telomeres and oxidative stress are believed to play an important role in aetiology of complex chronic disorders like diabetes, atherosclerosis (ATS), cardiovascular disease (CVD) and their complications.  The effect of oxidative/nitrosative stress on telomere dynamics is an important field of research. Even more, when the studied disorders are type 1 diabetes (T1D) and hypercholesterolemia (HCH) representing the major morbidity and mortality contributors in developed world. The dynamics of telomeres in a group of children and adolescents with T1D and HCH will be the main focus of our project. Participants with T1D will be grouped according to the manifestation of T1D complications. Participants with HCH will be additionally sub-grouped according to the genetic background of the disease and statin treatment. Studies on TL in paediatric populations are limited. There are far less accompanying diseases present in the paediatric population enabling clearer interpretation of results and identification of basic disease aetiology compared to the adult population. Our aim is to evaluate TL in correlation with 1) clinical data of participants, 2) oxidative stress biomarkers and 3) genetic predisposition for oxidative stress and telomere stability management. Identification of additional biomarkers of oxidative and nitrosative stress (i.e. 8-hydroxy-2-deoxy-guanosine, 3-nitro-tyrosine) will enable us to determine physiological conditions of telomere shortening in a group of chronically ill children. Results of this part of the project will be the basis for in vitro structural studies researching influence of reactive species on the telomere structure.  The newly obtained data will enable us to identify patients with potentially higher risk for developing early chronic complications of T1D and HCH. Identification of these patients in pre-clinical stage will enable us to design specific preventive strategies and thus significantly decrease the early morbidity and mortality of these devastating conditions. Proposed project is based upon multidisciplinary methodology, believed to be a cornerstone in development of personalized medicine approaches in the disease management. Understanding the oxidative stress influence on telomere dynamics, length and structure will significantly improve basic knowledge on the field.
Significance for science
Proposed project was based upon multidisciplinary methodology, believed to be a cornerstone in development of individualized management of disease. Understanding the oxidative stress influence on telomere length, telomere attrition dynamics and telomere structure had significantly improved basic knowledge on the field. We proved that poor management of type 1 diabetes translates relatively quickly after the disease onset into the accelerated rate of telomere attrition, potentially mediated by an excessive amount of nitrogen reactive species. The lost telomere length most likely cannot be redeemed and may potentially lead to type 1 diabetes complications. Additionally, shorter telomere length were related to increased risk for development of atherosclerosis and cardiovascular complications in children with hypercholesterolemia as soon as in preclinical phase of the disease, since aorta stiffness was only implied. Patients with causative mutation for familial hypercholesterolemia did not have shorter telomeres compared to the patients with polygenic hypercholesterolemia. This implies that elevated levels of cholesterol have greater impact on the telomere attrition than the genetic cause for this elevation. Evaluation of this knowledge together with clinical characteristics, oxidative stress biomarkers and genetic predisposition for oxidative stress management will bring important new basic knowledge on aetiology of complications in both disorders as well as provide further new clinically relevant knowledge. Studies on this carefully selected and clinically well determined cohort of patient had contributed to prediction of the disease progression and development of disease complications. This has an important role in clinical management of the disease.
Significance for the country
The study had supplemented basic knowledge and clinically relevant new knowledge. These results contribute to the possibility of risk determination and early identification of individuals at higher risk for development of type 1 diabetes and hipercholesterolemia complications, such as arthrosclerosis and cardiovascular diseases. Those together are the leading cause of morbidity in developed world. Therefore, early prevention of complications and late sequel with design of specific preventive strategies would be possible and with it significant decrease in the early morbidity and mortality of these conditions. In long term, the results may indirectly improve the medical service provided to patients with hypercholesterolemia and type 1 diabetes, and further development of early and/or individualised treatment and possible prevention of disease complications. With this, increase of the quality of life of patients and their families would be possible, decrease of the amount of working days lost by the caregivers and adult patients and decrease of direct and indirect costs related to this pathology.
Most important scientific results Annual report 2014, 2015, final report
Most important socioeconomically and culturally relevant results Annual report 2014, 2015, final report
Views history
Favourite