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.
BIOLOGICAL PROCESSES
OF AGEING
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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