The Pharmaceutical Journal
Vol 269 No 7218 p488
5 October 2002

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British Pharmaceutical Conference 2002 summary

Keynote address: We are programmed to survive, not die

Humans live, on average, about twice as long as they did 200 years ago, Professor Tom Kirkwood, head of the department of gerontology, University of Newcastle, told the Conference. This is a span only eight human generations long and some of the oldest people alive today have lived through more than half of it, he said.

"Life expectancy has increased by around 10 years over the past 50 years — this is the equivalent of getting around 20 per cent more life for free — and there is no maximum limit in sight," Professor Kirkwood said. Children born today have around an 85 per cent chance of reaching their 65th birthday.

"As we grow older we become increasingly frail and more likely to die. Ageing is not a process that kicks in around 40 though, it begins early in life. Mortality is relatively high in infancy. It falls to its lowest around puberty but after that rises in a progressive trend. There is a blip in the 20s, mostly caused by extrinsic factors, such as lethal mixtures of alcohol and fast cars in young men. Ageing presents a challenge to society and an opportunity for the pharmaceutical industry," he said.

"We will be having more and more experience of frailty and ill-health of old age and we will want to make the best of our extra years."

Why ageing occurs

"We are not programmed to die," Professor Kirkwood declared. "It is tremendously important that we recognise that nothing in the body is designed to bring about ageing. We are programmed for survival. Every cell and organ in our bodies works throughout our lives to keep us alive, even in old age. Indeed, some continue to work after we die as it takes a while for the message to spread." Apoptosis (programmed cell death) is a survival mechanism because it gets rid of damaged cells.

"Our harsh ancestral environment provided limited selection opportunities for long-term survival and health in old age. Our environment has changed while our bodies have not. As one American professor put it: 'We are stone-agers in the fast lane'." It is the limitations in the body's survival mechanisms that cause us to age.

Professor Kirkwood said that ageing is driven by an accumulation through life of random molecular damage. An accumulation that eventually manifests itself as functional impairments in organs and tissues. The body starts out as a single cell — "usually in good shape as there are lots of quality control mechanisms" — that eventually divides and specialises so that the adult human body consists of over 100 million million cells.

Ageing is related to three things — stress, damage and repair. Stress is the intrinsic biochemical stress suffered by individual cells and damage is what results from that. Damage and repair are dynamic processes. "There is a huge amount of activity going on in your cells — there is a war going on in your body. It is estimated that each cell gets 10,000 oxidative hits to its DNA each day, but around 9,997 will be put right by our repair mechanisms," he said.

Professor Kirkwood said that it was important to realise that there are multiple mechanisms that contribute to the ageing of cells. "There is not even a primary mechanism but a network of them." The processes are complex and there is a need to integrate the research on individual mechanisms. Finally, it is crucial to realise that there is a lot of randomness and chance in the process and that what happens to one cell may not affect its neighbour.

Turning to some of his own research, Professor Kirkwood said that investigations in mice of stem cells found in crypts of the gut showed that these cells, from which all other cells could be formed, become much more sensitive to stress as they age. Gene expression is delayed and there is an impaired regenerative capacity following DNA damage.

Ageing and age-related disease

One of the problems with ageing is to differentiate between normal ageing and age-related disease. For example, osteoporosis is known to be caused by a loss of bone mineral density due to impairment of osteoblasts. But everyone loses bone mass over the years. Why do some people cross the threshold regarded as osteoporosis?

Looking at Alzheimer's disease, Professor Kirkwood said that this was now recognised as a specific disease rather than just being classed as part of general senile dementia.

"Recognition as a specific disease has decreased the stigma of dementia and increased the recognition of the role of carers. However, as soon as it is labelled as a disease there must be the prospect of a 'cure'. There is increased support for, and willingness to undertake research in the area and increased pharmaceutical industry interest."

He said that Alzheimer's was now recognised as the single most common cause of senile dementia, account for just over half of all cases. Dementia with Lewy bodies, the same bodies seen in Parkinson's disease, had also been recognised as a distinct disease, making up about 20 per cent of cases. However, lesions similar to those seen in both diseases could be seen in the brains of non-demented adults.

Genes of ageing

"Studies have shown that genes account for around 25 per cent of what determines human longevity. The other factors are nutrition, lifestyle, environment and chance," he said.

Different foods and nutrients can have either positive or negative effects on cells, contributing to health and longevity or subtracting from it. The health enhancing benefits of exercise are well known. The environment in which people live can have powerful enabling or disabling effects. An unsupportive environment, with poor housing and transport and high crime, can lead to a rapid downward spiral in the health and lives of the elderly.

"We also have to recognise that our lifespan is partially determined by factors over which we do not have control."

In conclusion, Professor Kirkwood said that there are a number of problem attitudes towards ageing that need to be addressed. These include fatalism ("we are all going to die anyway"), denial of ageing, negative stereotyping of the elderly, tunnel vision, abdication of personal responsibility and the fantasy of a "quick fix pill" which will solve all our problems sometime in the future.

What is needed is a recognition of the continuum of ageing, to confront the issues of personal choice, target barriers to healthy old age and identify realistic outcomes in old age.

"Above all, we need to celebrate longevity — one of humanity's greatest achievements," he concluded.