Oxidative Stress and Ageing Mechanisms
Oxidative Stress and Ageing
The actions of oxygen radicals and reactive oxygen species are thought to play a key role in the ageing processes of many species. These SPARC projects encompass the areas of radical detection, radical susceptibility and radical defence.
EPR, oxidative stress and ageing
Dr Richard Hartley, Glasgow University
18 months, £58,534
General Poster: Oxidative Stress & Ageing, Scientific Poster
Executive Summary: EPR, Oxidative Stress and Ageing
Keywords: Electron Paramagnetic Resonance, Detecting Radicals, Protecting Cells, Understanding Ageing
Cells age for many reasons. They can be damaged by radicals, particularly oxygen-centred radicals causing pathologies such as arterioscelerosis, neoplasma and cataracts and play a role in stroke, neurodegeneration and autoimmune diseases. Understanding the biological sources of radicals, their behaviour in different environments and the cellular responses to them is a key to understanding the ageing process and ameliorating the diseases of old age. The study will develop new techniques using EPR spectroscopy for detecting radicals at the sites where they cause most damage.
Application of high-throughput assays of oxidative stress to studies of the role of common genetic variation in healthy human ageing
Professor Paul Winyard, Exeter University
12 months, £56,851
Poster: The Genetics of Ageing
Keywords: Genetics, Oxidative Stress, Biomarkers, Loss of Function
Family and twin studies of ageing have shown that genes are important in determining who ages well and who does not. However, a current limitation of these genetic studies is that statistical associations between healthy ageing and particular inherited gene variants cannot easily be backed up by direct evidence of biochemical changes in ageing pathways. One key theory of ageing holds that ageing-related oxidative damage to cellular components is responsible for declining human function. We propose to establish high-throughput assays of oxidative damage biomarkers (suitable for the analysis of thousands of human blood samples) so that we can begin to assess the effects of candidate, ageing-related, gene variants on oxidative damage. We believe this will provide the necessary tools for major advances in understanding the role of oxidative stress in human ageing.
The ageing process is a something which humans share with the vast majority of other species on the planet. Ageing evolved at least a billion years ago and has been part of the genetic inheritance of species ever since. Studying the basic mechanisms of ageing in proteins, cells, tissues and animals, allows us to understand how they operate. This basic information will enable further research to take place, aimed at preventing the degenerative effects of these processes.
A proteomics approach to understanding age-related changes in neuronal function
As cells age so there is a change in the number of connections a neuron makes with a target cell, and this may contribute to neurodegeneration. It is clear that ageing is associated with significant changes in relatively few proteins but this is an area which has been hardly examined. So, this study will provide new information concerning the role of changes in protein expression in neuronal ageing.
Gene expression profiling to understand stem cell ageing
Dr Ilaria Bellantuono, Sheffield University
10 months, £28,288
Poster: Stem Cell Ageing
Executive Summary: Gene Expression Profiling to Understand Stem Cell Ageing
Keywords: Neural Stem Cell, Haemopoietic Stem Cell, Ageing, Microarray
Stem cells (SC) are present in all organs and are responsible for the maintenance of their function. With time their ability to carry out these tasks is decreased and in some cases this results in the occurrence of disease. Down's syndrome (DS) shows signs of premature ageing with features found commonly in older people such as Alzheimer disease. We have studied SC in DS fetuses and children and found that they have similar characteristics to older individuals. In this project we propose to use DS SC from brain and blood to identify genes that are important in loss of SC function with age.
Unnatural ageing of killer cells
Dr Donald Palmer, Royal Veterinary College
12 months, £36,765
Poster: Ageing of Natural Killer Cells
Keywords: Natural Killer Cells, Immunosenescence, Ageing, Innate Immunity
The ability to fight and be protected against infectious agents is dependent upon a fully functional immune system. However, functional immunity declines with age, leading to various clinical manifestations. Cells known as Natural Killer (NK) cells play a central role in the immune system and we believe that their function declines with age. To test this hypothesis we will compare what NK cells look like from young and elderly individuals. We will also compare their functional activity. These studies will help determine the contribution that NK cells play towards the age-associated changes in immunity.
An investigative approach to define a role for endothelial nitric oxide synthase in the vascular biology of ageing and consequences for cardiac function
With increasing age the risk of developing high blood pressure that is not controlled by available therapies and heart failure is dramatically increased. This project seeks to understand the complex interactions between changes in the properties of the specialised cells lining blood vessels, the endothelial cells that produce nitric oxide thereby contributing to the control of blood pressure, and the function of the heart. By understanding how these interactions change with advancing age better treatments for controlling blood pressure may be possible. Furthermore, by determining how the function of the endothelial cells of blood vessels changes and how this influences the function of the heart it may be possible to define the link between ageing and the development of heart failure.