Thomas B L Kirkwood1,2. 1. University of Copenhagen Center for Healthy Aging, Department of Cellular and Molecular Medicine, Copenhagen, Denmark. 2. Newcastle University Institute for Ageing, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
Abstract
NEW FINDINGS: What is the topic of this review? The reasons for the continuing increase in human life expectancy are examined in the light of progress in understanding the physiological basis of ageing. Prospects for further extending the health span - the period free of age-related disability and disease - are critically assessed. What advances does it highlight? No active programming directly causes ageing, which instead results as a side effect of how evolution optimises the physiological allocation of resources between growth, reproduction and maintenance. Under pressure of natural selection, there was insufficient priority in maintaining the body well enough that it could endure without progressive accumulation of multiple kinds of molecular and cellular damage. Understanding human ageing is a major challenge for the physiological sciences. It is made all the more urgent by the survival of inreasing numbers of people to advanced old age and by a shift in the underlying causes of the continuing increase in life expectancy. The previous increase was caused almost entirely by the prevention of deaths in the early and middle years of life; a process that has seen such success that in developed countries there remains little scope for significant further increase from this cause. The more recent increase is driven by something new. We are reaching old age in generally better health, and it is the death rates at advanced ages that are now falling fast. At the same time, biology has established that there is almost certainly no fixed programme for ageing, which is caused instead by the lifelong accumulation of damage. It is becoming evident that the ageing process is much more malleable than we used to think. We need urgently to establish the factors that govern this malleability and to identify the interactions between, on the one hand, intrinsic biological processes that drive the many chronic diseases and disabilities for which age is by far the largest risk factor and, on the other hand, the social and lifestyle factors that influence our individual trajectories of health in old age. Ageing is no longer as mysterious and intractable a process as used to be thought, offering new opportunities for contributions from other branches of the physiological sciences.
NEW FINDINGS: What is the topic of this review? The reasons for the continuing increase in human life expectancy are examined in the light of progress in understanding the physiological basis of ageing. Prospects for further extending the health span - the period free of age-related disability and disease - are critically assessed. What advances does it highlight? No active programming directly causes ageing, which instead results as a side effect of how evolution optimises the physiological allocation of resources between growth, reproduction and maintenance. Under pressure of natural selection, there was insufficient priority in maintaining the body well enough that it could endure without progressive accumulation of multiple kinds of molecular and cellular damage. Understanding human ageing is a major challenge for the physiological sciences. It is made all the more urgent by the survival of inreasing numbers of people to advanced old age and by a shift in the underlying causes of the continuing increase in life expectancy. The previous increase was caused almost entirely by the prevention of deaths in the early and middle years of life; a process that has seen such success that in developed countries there remains little scope for significant further increase from this cause. The more recent increase is driven by something new. We are reaching old age in generally better health, and it is the death rates at advanced ages that are now falling fast. At the same time, biology has established that there is almost certainly no fixed programme for ageing, which is caused instead by the lifelong accumulation of damage. It is becoming evident that the ageing process is much more malleable than we used to think. We need urgently to establish the factors that govern this malleability and to identify the interactions between, on the one hand, intrinsic biological processes that drive the many chronic diseases and disabilities for which age is by far the largest risk factor and, on the other hand, the social and lifestyle factors that influence our individual trajectories of health in old age. Ageing is no longer as mysterious and intractable a process as used to be thought, offering new opportunities for contributions from other branches of the physiological sciences.
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