Intervening in ageing to prevent the diseases of ageing

Increases in human lifespan worldwide have revealed that advancing age is the predominant risk factor for major life-threatening diseases. Recent work has shown that ageing in diverse animals, including humans, is malleable to specific types of genetic mutation, diet, and drugs that can extend lifespan and improve health during ageing. These findings point to the prospect of broad-spectrum preventive medicine for the diseases of ageing based on intervention in relevant aspects of the ageing process itself. Increases in human lifespan worldwide have revealed that advancing age is the predominant risk factor for major life-threatening diseases. Recent work has shown that ageing in diverse animals, including humans, is malleable to specific types of genetic mutation, diet, and drugs that can extend lifespan and improve health during ageing. These findings point to the prospect of broad-spectrum preventive medicine for the diseases of ageing based on intervention in relevant aspects of the ageing process itself. Human populations in developed countries, and in many developing ones, are getting older. Human life expectancy at birth has been increasing by about 2.5 years per decade since the middle of the 19th century, with no demographic hint so far of an intrinsic limit to human lifespan [1Oeppen J. Vaupel J.W. Demography. Broken limits to life expectancy.Science. 2002; 296: 1029-3101Crossref PubMed Scopus (1603) Google Scholar]. This sustained trend has been brought about by successive contributions from lifestyle and medical care, including improvements in water and food quality and the prevention of many infectious diseases, which is particularly important for increased survival in children. Recently, improvements in medical care have played an important role, with increasing survival now occurring almost entirely in older age groups, although there is growing evidence that these health benefits are not evenly distributed across different sections of the population [2Olshansky S.J. et al.Differences in life expectancy due to race and educational differences are widening, and many may not catch up.Health Aff. (Millwood). 2012; 31: 1803-1813Crossref PubMed Scopus (470) Google Scholar]. Although increases in health and lifespan are to be celebrated, they come with several downsides. Some of these are economic. In many countries increased lifespan is accompanied by falling birth rates and hence a rapid increase in the proportion of the population that does not participate in the labour force. There is also debate about the extent to which increasing lifespan is also increasing health span [3Fries J.F. et al.Compression of morbidity 1980-2011: a focused review of paradigms and progress.J. Aging Res. 2011; 2011: 261702Crossref PubMed Scopus (185) Google Scholar]. However, the main problem of longer lives is that increasing age is proving to be the major risk factor for all of the common chronic and killer conditions of the developed world: metabolic, cardiovascular, and neurodegenerative disease and cancer [4Niccoli T. Partridge L. Ageing as a risk factor for disease.Curr. Biol. 2012; 22: R741-R752Abstract Full Text Full Text PDF PubMed Scopus (884) Google Scholar]. The major burden of ill health is hence now falling on the older section of the population and their carers and there is an urgent need to find ways of keeping people healthy for longer. Because ageing is the major risk factor for all of these diseases, one obvious approach to maintaining the health of older people would be to intervene in the underlying ageing process itself. The intrinsic rate of ageing can be drastically altered by (presumably complex) genetic change, because there is great diversity in the natural lifespans of animals, even when they are brought into environments where they are largely protected from extrinsic hazards. For instance, among mammals, bats, primates, and whales are notably long lived [5Nussey D.H. et al.Senescence(definition) in natural populations of animals: widespread evidence and its implications for bio-gerontology.Ageing Res. Rev. 2013; 12: 214-225Crossref PubMed Scopus (440) Google Scholar]. Scientific discoveries from research into ageing in recent years have also suggested that intervening in human ageing is more plausible than it once seemed. Although ageing is complicated and variable, with diverse kinds of damage and pathology accumulating in a way that varies between both different body tissues and individual organisms, the process has nonetheless proved to be malleable. Both genetic mutations and environmental interventions such as altered diet and drugs can increase lifespan and health during ageing in laboratory organisms (yeast, nematodes, fruit flies, and mice). Furthermore, despite the very different lifespans and lifestyles of these creatures, similar interventions have proved capable of extending health span in all, implying some commonalities in the underlying mechanisms of ageing. Simpler organisms with shorter lifespans can thus contribute to an understanding of the mechanisms of mammalian, including human, ageing, and to the discovery of interventions that could ameliorate it [6Kenyon C.J. The genetics of ageing.Nature. 2010; 464 (erratum in Nature 467, 622): 504-512Crossref PubMed Scopus (2031) Google Scholar, 7Fontana L. et al.Extending healthy lifespan – from yeast to humans.Science. 2010; 328: 321-326Crossref PubMed Scopus (2168) Google Scholar, 8Partridge L. The new biology of ageing.Philos. Trans. R. Soc. Lond. B: Biol. Sci. 2010; 365: 147-154Crossref PubMed Scopus (107) Google Scholar]. The ageing process remains a considerable biological mystery. Virtual immortality of cell lines is clearly possible because all current life on earth originated from a common ancestor, as evidenced by the use of a common genetic code. Germlines, therefore, do not have to die. Also, some multicellular organisms, such as Hydra and some sea anemones, do not become less able to reproduce or more likel