The Pharmaceutical Journal
Vol 269 No 7218 p490
5 October 2002

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British Pharmaceutical Conference 2002 summary

Fundamentals of ageing: How our body tissues change with age

Physical ageing is obvious, but it is not possible to determine a person's state of cognitive function from their physical appearance, said Dr Beatrice Ward, Babraham Institute. There are various theories on the key to indicating cognitive decline, including attention, working memory and flexible responding, but the only hypothesis that holds true is the speed of responding — this declines with increasing age.

Dr Ward presented data from a mouse model used to explore attentional processes. Initially, it was thought that a reduction in the number of neurones was responsible for decreased attentional processing, but now the functional status of the existing neurones and their connectivity are known also to be important. The mouse model involves using a light stimulus; if the mouse responds to the stimulus in the correct way, then it can collect a reward. Various measurements can be made, such as whether mice can learn the task, and the number of sessions taken to learn the task.

Summing up some of the findings of this work, Dr Ward said that older mice were impaired in the early stages of the learning process, and that healthy ageing impacts on the speed and accuracy of cognitive processing in the attentional domain. Her take-home message was that mental as well as physical exercise may be important in staying healthy in ageing.

B cell ageing

Dr Deborah Dunn-Walters, department of histopathology and immunobiology, Guy's, King's and St Thomas' School of Medicine, London, discussed research into mechanisms of B cell ageing. Older people are more susceptible to infectious disease, and morbidity and mortality from infections increase sharply over the age of 65 years; at the same time, the efficacy of vaccinations in older people is reduced. This knowledge points to an age-related dysregulation of the immune system. Evidence suggests that the change in the humoral immune response with age is qualitative rather than quantitative — the affinity and specificity of the antibody change rather than the quantity of antibody produced. There are several possible causes of this:

• A decrease in quantity/diversity of fresh B cells able to cope with new antigen challenge

• A failure of B cells to be activated in response to antigen

• A defect in the mechanism of hypermutation of immunoglobulin genes

• A defect in the mechanims that select B cells carrying high affinity B cell receptors

Dr Dunn-Walters described her work studying the diversity and hypermutation of rearranged immunoglobulin genes. The results indicated that there is no difference in the actual mechanism of hypermutation with age, but that there are differences which may be due to a change in the B cell selection process, or to a change in the founder cells available for activation.

Muscle ageing

There is an age-related functional deficit in skeletal muscle and a loss of muscle bulk, ie, muscle becomes smaller and weaker with increasing age, said Dr Ann McArdle, department of medicine, University of Liverpool. In addition, remaining muscle is more susceptible to damage, particularly following exercise, and recovery from damage is impaired.

The mechanisms by which skeletal muscle damage occurs are poorly understood. However, there is some evidence suggesting that an increased production of free radicals may act the adaptive response in skeletal muscle, leading to an increased production of antioxidant enzymes and heat shock proteins (HSPs). The increased protein aids rapid remodelling of muscle and to some extent protects against subsequent muscle damage.

According to Dr McArdle, the production of free radicals is modified during ageing, and this may affect the ability of muscle cells to respond to stress. Studies involving muscles from adult rats showed significantly increased concentrations of HSP 70 following contractile activity compared with non-exercised muscle.

This increase in HSP is not evident in muscles from aged rats. The attenuated response may be important in the development of age-related functional deficit in skeletal muscle

Dermal ageing

Dr Ian Kill, Brunel University, London, described his group's work in reconstructing dermis using young and aged (senescent) rat dermal fibroblasts seeded into an acellular fibrous collagen matrix derived from young or aged rat skin.

Their key findings are that there are no differences between young and aged fibroblasts in terms of their attachment to young or aged collagen, but that there are differences in the levels of migratory activity into collagen. Young fibroblasts infiltrated aged collagen more readily than they infiltrated young collagen, and aged fibroblasts infiltrated young or aged collagen more readily than did young fibroblasts. Further studies, involving grafting young and aged collagen into recipient rats showed that grafts are incorporated regardless of the age of the collagen donor.

Geronomics

Dr Jonathan Powell (Unilever) said, in his view, the "gold standard" for delaying ageing is dietary manipulation, specifically caloric restriction. He referred to experimental studies suggesting that around 50 per cent of age-related changes in gene expression are "rebalanced" in caloric restriction.

However, further research is needed. Dr Powell said he does not believe that proteomic technology is anywhere near ready for use yet in this area.
— Contributed by Dr Jo Barnes, School of Pharmacy, University of London.