The Foundation aims to create biomedical interventions to address the deleterious alterations which occur in the bio-molecules and cells of the body as a side effect of normal metabolism (often referred to as “ageing damage”), and which accumulate over the course of life, eventually causing the diseases of ageing.
An example of such an alteration is the “cross linking” of protein molecules by molecules of sugar. Such reactions impair the protein’s function, and because the body cannot repair all of these alterations, their number increases with age. Many important physiological proteins are affected by this process, leading to numerous pathological outcomes (e.g. collagen, a protein, and a constituent of artery walls, becomes stiffened, leading to raised blood pressure). In this example the Foundation will research potential methods of “breaking” the crosslink, or removing the cross-linked structure altogether. If we can show that this is possible, we will be a step nearer to treatments for the many diseases that are caused in part by cross-links, and will have demonstrated to other researchers that this is a problem they can work on and help to solve. From our experimental outcomes we will learn more about cross-links, their effects on the body, and hence how those effects could be minimized.
Many researchers are investigating the chain of biochemical events which lead to the symptoms of the diseases of ageing, to find points along the pathway where drugs or treatments can intervene, thereby relieving those symptoms. This approach has produced many invaluable treatments for the victims of ageing diseases, but does not address the underlying lesions which continue to accumulate.
Regenerative therapies based on stem cell technology are also being pursued; this area is well funded elsewhere, and moreover is not applicable to all the body’s systems.
There are also currently a number of approaches which aim to discover ways to slow down the progressive impact of ageing on health by modifying metabolism: investigators compare the metabolism of short-lived species of animals with that of longer-lived, but otherwise similar, animals, in order to determine what biochemical features are associated with a slower ageing rate. Similarly others gain insights by examining how differing lengths of lifespan (and therefore rates of ageing) evolved. Others breed increasingly long lived strains to observe the resulting changes in metabolism which enable longer healthy life.
Perhaps the most widespread such approach is to investigate the changes in metabolism which occur in many animals when calories are restricted in their diet. It is known that calorie restriction reduces the incidence of age-related disease and extends maximum lifespan in many species; by understanding this phenomenon scientists hope to find ways to recreate the effect in humans without the need for a low energy diet.
However, the “slowing down ageing” approach faces the obstacle that many of the biochemical reactions which cause ageing damage are themselves essential to life and cannot be moderated below a minimum level. So while ‘fine-tuning’ our metabolism for longevity may be achieved relatively easily (and is currently available to some extent, albeit at the expense of rigorous diet control), this is not likely to do more than postpone the diseases and disabilities of age by a few years. Importantly, this approach will slow, but not halt, the accumulation of underlying damage, and be of lesser benefit to those already aged.
In contrast, many of the types of molecular and cellular lesions which are the result of the ageing process are well characterised, so while we cannot stop them accumulating, we can envisage ways of removing or remediating them once they are there. The BGRF will therefore support primarily biotechnological approaches to damage reduction and removal. Further, since ageing damage is foreign to the body its post-therapy absence is less likely to trigger metabolic counter-adaptation, (although the treatment process itself may have side effects which we must work to minimise). Since this damage is a fundamental cause not just of symptoms but of the underlying disease, removing it will move us closer to a genuine cure.
As with all research the time taken to produce results cannot be precisely foreseen. However the BGRF aims to develop biotechnologies to remediate known molecular and cellular lesions, an approach which does not require the full elucidation of metabolism, nor of the ageing process itself, but rather takes the pragmatic route to develop treatments. This should produce effective therapies in the shortest time possible, while useful interim products and technologies may be generated during the research process.
The BGRF will fund research at those laboratories in the UK and around the world which are at the forefront of the relevant research areas. Because we are taking a pragmatic, biotechnological approach to new treatments, these laboratories could well be those considered to be developing new technology, rather than those researching drugs. Examples could include laboratories working on:
Thus it is likely that new projects will be multi-disciplinary, pulling together several components of new technologies and helping researchers to test them,at first separately and then in combination. Each such project is a major task, and working cooperatively with other organisations will be essential. The BGRF will therefore take a lead role in identifying key laboratories in the UK, Europe and elsewhere, and bringing together technologists and scientists to collaborate on this exciting new work. The BGRF intends to include the appropriate regulatory agencies as early in the collaboration as possible.