During the last decades of the 20th century, a remarkable phenomenon became apparent. Contrary to general expectation, the increase in human life expectancy - a measure of average length of life within the population - that had been occurring steadily in developed countries for almost two centuries failed to hit its predicted ceiling and has carried on at the same rate as before. To appreciate why the continuing increase in life expectancy was unexpected, it is necessary to examine what had been driving its earlier increase: cleaner drinking water, better sanitation and improvements in housing, education and nutrition all contributed, aided latterly by the development and widespread application of vaccines, antibiotics and other advances in preventive and therapeutic medicine. As the last quarter of the 20th century began, the residual levels of early- and mid-life mortality had fallen so low that any further reductions could have had only a modest effect on further increasing life expectancy.
As it was assumed that the ageing process itself was essentially immutable - a biological given - it was expected that populations would simply contain greater numbers of older people. These would die at the same ages as the oldest of their predecessors, who had been fewer in number but aged just the same. What has changed, however, is that it is now the death rates of those of advanced age - 80 and older - that are falling fastest. Put simply, it seems that the nature of old age is undergoing a significant change. Old people are, as a rule, reaching more advanced ages in better and better condition, and this is reflected in the continuing increase in life expectancy. What is likely to happen to human longevity in the future? What factors influence our individual trajectories of health into old age? How feasible is it to think of discovering new ways to extend further the duration of healthy life free of disability and disease?
The evolution of ageing is now generally understood to have occurred not through programming of ageing as an adaptive benefit in its own right, but because the force of natural selection falls off strongly across the course of the lifespan. The different longevities of different species can be explained because the exposure to accidents varies from one species to another, and consequently, selection will favour a higher investment in somatic maintenance in a species better adapted to survive the hazards of its ecological niche than in a species subject to a higher extrinsic level of risk. Comparative studies of ageing consistently reveal that cell maintenance is greater in longer-lived organisms.
A striking feature of ageing is its variability. That ageing is malleable is evident from the falling death rates in old age. The more hygienic conditions of modern life in high-income countries, with fewer sources of physical stress and earlier interventions to maintain health, most probably explain why people now reach old age physically 'younger' than their parents and grandparents. Malleability is also evident through the social gradient in health and life expectancy, whereby those of lower socio-economic status have shorter life expectancy.
Recent progress in research on ageing has generated considerable interest in the potential for science to extend the human health span, i.e. the period free of significant disease or disability, beyond the improvements that are occurring already. These include the possibilities of the following: (i) drugs targeting molecular pathways found to be involved in the regulation of lifespan, such as rapamycin and resveratrol, or enzymes such as telomerase; (ii) control of food intake through dietary restriction or intermittent fasting, to mimic longstanding observations on the life-extending effects of caloric restriction in rodents; (iii) so-called 'senolytic' strategies selectively to remove senescent cells from aged tissues and organs; (iv) transfer of plasma or serum from young to old individuals, based on pioneering studies using pairs of young and old rodents whose circulatory systems were connected; (v) repurposing of existing drugs, such as metformin, previously licensed for treatment of diabetes and now of interest for potential anti-ageing properties.
Despite the exciting potential for progress, it is important to reflect briefly on the main challenges confronting the attempts to extend the health span. The regulatory framework within which new interventions to extend health span can be developed raises particularly interesting challenges. When targeting illness, especially if it is painful and life limiting, the barriers against accepting possible side-effects are lower. Thus, anti-ageing interventions will most easily gain approval if they target late-stage diseases. However, these are not the interventions that will most effectively extend the health span. The latter interventions are ones that would need to be introduced before or as soon as possible after the earliest signs of age-related health deficits become apparent. They will therefore also be candidates for application across the population at large.
It is as yet uncertain to what extent and when science will deliver improvements in health span. Given what we know already about the general nature of the ageing process and of its malleability, it seems entirely reasonable, indeed probable, that improvements of this kind will occur. It would be wise, however, not to promise or expect too much too soon. However, the same science is likely to provide further evidence to support and encourage the kinds of changes in nutrition and lifestyle that are already known to be effective, and here it is reasonable to expect benefits to occur faster.