Select Committee on Science and Technology Written Evidence

Memorandum by Professor Michael Rennie

  I am Professor of Clinical Physiology at the University of Nottingham Graduate Entry Medical School in Derby. Previously from 1983 to October 2003 I was Professor of Physiology at the University of Dundee. I have approximately 30 years experience of human metabolic research, supported by major medical charities and the research councils; I have produced 210 papers in the refereed literature plus about 40 book chapters.

  I would like to give evidence on the biological processes of ageing promising avenues for research, small benefits, effectiveness of research co-ordination, priorities, gaps and research capability in the UK and the use of the research to inform policy on the basis of current evidence.


1.   What are promising avenues for research?

  For any biological phenomenon the observed variation in the way that phenomenon presents itself is about 50 per cent due to environment and 50 per cent due to genetic pre-disposition. It seems likely that given a particular genetic pre-disposition, manipulation of lifestyle can help maintain physical and mental activity optimally into old age. Such broad brush statements are however little use in practical terms because we need to be able to make specific recommendation, for example in terms of diet (constituents, type, amount) and exercise (aerobic or resistance, amount). However, the evidence base upon which to make such recommendations is very poor. We really have very little understanding of what an optimal diet is for a healthy, active 70 year old woman in comparison with a healthy, active 80 year old woman or a 50 year old man. What recommendations should we be making about protein:energy ratios in the diet? Calcium intake? Zinc intake? Vitamin supplementation? Would it better for the healthy, elderly to do aerobic exercise or would they be better off doing resistance exercise as some of the emerging literature suggests? What are the benefits of changing lifestyle in the fifth decade? Is it a waste of time and should we be concentrating on optimising the health of our children in order to avoid not only obesity, which is a recognised problem, but osteoporosis and muscle wasting in later life?

  All of these questions constitute promising lines of research which are important because they do not unnecessarily medicalize old age and certainly do not involve drug treatment. The problem with drug treatment for conditions associated with ageing is that so far none of the available drugs are particularly efficacious including drugs for osteoporosis which may make bones heavier but have very little effect in improving their toughness and resistance to fracture. Providing an evidence base for interventions which actually make a difference in increasing health during ageing is important because it is likely to be cheaper than the alternative, which are to use expensive drugs which we could not afford on a population basis. We must do the research to find out what works and disseminate the results among opinion formers, policy makers and the ageing population this is likely to have a much higher cost benefit ratio than, for example attempting to develop anti-ageing pharmaceuticals.

2.   Priorities

  I firmly believe that we need to do more research in human beings rather than concentrating on animal models of ageing. Let me give an example of an animal model of ageing which has produced a totally un-human like result. Muscle wasting, ("sarcopenia"), is a common consequence of ageing from the fifth decade onwards. We have recently carried out studies which have been published in preliminary form (Cuthbertson DJR, Babraj JA, Atherton, PA, Wackerhage H, Smith et al. The muscle of elderly men showed resistance to stimulation of myofibrillar proteins synthesis (MPS) by essential mineral acids (EAA a) as result of loss of capacity and sensitivity of protein synthetic machinery and altered nutrient signalling. FASEB (J 18. 2004) which show that muscle maintenance processes in the elderly are not as efficient as in the young because elderly people are unable to use of dietary protein as well as young subjects—they have what we call "amino acid resistance". This means that in a 24 hour cycle in which losses of muscle protein would in young people be replaced by meal stimulated processes there is a decrement of a few per cent which leads to loss of maintenance of muscle.

  Recently, however, a paper has been published in the American Journal of Physiology dealing with a colony of very old rats. These rats are also sarcopenic but contrary to the behaviour of old human beings these rats show what amounts to an inflammatory response in which muscle protein turnover is revved up but with breakdown processes going faster than the synthetic processes. This picture is similar to that seen in rats, mice and other rodents in response to end stage wasting of muscle in many disease states. It is not a good model for human ageing.

  Please note I am not arguing here for the application of old fashioned methods—we should be using the best available modern genomic and proteomic and metabolic approaches—but in people so far as possible.

3.   Gaps

  In my view there is insufficient drive to use modern methods of metabolic research in the elderly in the United Kingdom compared to, for example, the United States. There are certainly gaps in research concerning optimum nutrition and exercise patterns and these can only be answered by doing work in human beings rather than in animals. There are certainly insufficient research capability in the United Kingdom partly as a result of the Calman "reforms" which decimated clinical scientific research 10 years ago and because of the new managerial approach in the health service which has made it more difficult for junior hospital doctors to step off the training ladder to undertake clinical research fellowships. In addition there are only a handful of centres in the United Kingdom in which proper clinical scientific research concerning the elderly can be carried out with modern methods of metabolic investigation.

4.   Research co-ordination

  Research is poorly co-ordinated between the public, private and charitable sectors. For example although there is a research charity called Research into Ageing they are relatively cash poor and have to turn down many highly rated applications simply for this reason. There appears to be no co-ordination between the Medical Research Council and charities concerned with ageing and as far as I am aware there is no support for research into ageing from private sources. The BBSRC and its food and agriculture programme supports work on ageing but because of its strict remit which does not allow it to carry out research which can be classified as "medical" there seems to be no cross talk between the BBSRC and the MRC. Woe betide any applicant to the BBSRC who implies that the results may be used for example in the identification of new drug targets. This is obviously irrational.

5.   What should be done?

  First the research councils and the charities should sit down together and decide on research gaps, priorities and opportunities. They should then decide how much it would cost to fund the work and ask for bids in identified areas. The amount of resource required is likely to be of the order of £10 million per year for five years in the first instance.

  Secondly, co-ordinated fund raising by a consortium of charities interested in ageing and research would be more efficient that the current hotch potch.

September 2004

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