Dr Robert Butler (1927–2010) was the first director of the influential National Institute on Aging (NIA, USA). He is best known for his 1975 book Why Survive? Being Old in America, in which he exposed the marginalisation of older people. For a biography of this champion of older people’s rights, see:

Achenbaum, W.A. (2013). Robert N. Butler, MD: visionary of healthy aging. New York: Columbia University Press.

Chapter One
THE RHYTHM OF LIFE

An accumulation of damage

For a further introduction to the ageing process, I recommend the website of the biologist Dr João Pedro de Magalhães (Heswall, Wirral, UK), a source of inspiration with references to further information for beginners and advanced students:

Introduction to the ageing process: http//www.senescence.info/.

In his now-seminal lecture, given in London in 1951, the British zoologist and later Nobel Prize-winner (Medicine, 1960) Peter Medawar (1915–1987) describes the principle of the accumulation of damage as the basis of the ageing process:

Medawar, P.B. (1952). An Unsolved Problem of Biology. London: H.K. Lewis & Co.

All for the next generation

The conclusion of this section is that ageing ‘can’ only occur because natural selection is the dominant force at the beginning of the human life cycle. The evolutionary biologist Professor Stephen Stearns (Yale, USA) is one of the world’s greatest thinkers on the different phases of the (human) life cycle. His book is considered a standard reference work:

Stearns, S. (1992). The Evolution of Life Histories. New York: Oxford University Press.

A more recent book on the topic is:

Thomas Flatt and Andreas Heyland (Eds.) (2011). Mechanisms of Life History Evolution: the genetics and physiology of life history traits and trade-offs. Oxford: Oxford University Press.

The biologist Professor Steve Austad (San Antonio, USA) is one of the great names in the field of ageing. He stresses that (human) ageing is not just a phenomenon that (today) occurs under favourable conditions, but which occurred (in the past) under unfavourable conditions. He substantiates this with an overview of recent data gathered by biologists on many different animal species:

Nussey, D.H., H. Froy, et al. (2013). ‘Senescence in natural populations of animals: widespread evidence and its implications for bio-gerontology.’ Ageing Research Reviews, 12: pp. 214–25.

Rites of passage

The best description of the course of our life trajectories in different periods of human history can be found in a richly illustrated work put together by the historian Professor Pat Thane (London, UK). One of the most important points she makes is that the social status of old people differs from one historical period to another, and from culture to culture, and that it declines rapidly in times of economic depression. She postulates that it is a misconception that older people always enjoyed a high social status in the past:

Thane, P. (Ed.) (2005). The Long History of Old Age. London: Thames & Hudson.

The second issue dealt with in this section is the genetic basis for our life history. In it, I describe the different forms of the nematode (roundworm) C. elegans. Those forms cover a range — selective constraints — that can include environmentally triggered plasticity. The evolutionary biologist Paul Brakefield (Cambridge, UK), is the master of so-called ‘evo-devo’ (evolution of development) theory:

Brakefield, P.M. (2006). ‘Evo-devo and constraints on selection.’ Trends in Ecology & Evolution, 2: pp. 362–68.

Chapter Two
ETERNAL LIFE

Damage and repair

The rate of ageing is the result of an accumulation of damage on the one hand, and maintenance and repair on the other. These are two sides of the same coin. Below are references to the work in which it was observed that hydras do not age thanks to the presence of ‘totipotent’ stem cells:

Martínez, D.E. (1998). ‘Mortality patterns suggest lack of senescence in hydra.’ Experimental Gerontology, 33: pp. 217–25

Galliot, B. (2012). ‘Hydra, a fruitful model system for 270 years.’ International Journal of Developmental Biology, 56: pp. 411–23.

To be impressed by the enormous variation in lifespan — including the non-senescent hydra — see:

Jones, O.R., A. Scheuerlein, et al. (2014). Diversity of ageing across the tree of life. Nature 505:169–74.

Longevity in families

In the past ten to twenty years, researchers have developed various methods to help them discover the genetic basis for longevity. The first method is to look at people who are over a hundred years old — centenarians. The gerontologist Professor Claudio Franceschi (Bologna, Italy) has the most experience in this area of research. The second method is pursued by the endocrinologist Professor Nir Barzilai (New York, USA), who included only long-lived Ashkenazy Jews and their offspring in his study. The third method involves gathering information on families in which several nonagenarian siblings are still alive, and collecting data concerning their children and their partners. This last method increases the chance that the longevity of the participants is due to hereditory factors, and is followed by the Leiden Longevity Study, initiated by the biologist Professor Eline Slagboom (Leiden) and myself:

Cevenini, E., L. Invidia, et al. (2008). ‘Human models of aging and longevity.’ Expert Opinion on Biological Therapy, 8: pp. 1393–1405.

Atzmon, G., M. Rincon, et al. (2005). ‘Biological evidence for inheritance of exceptional longevity.’ Mechanisms of Ageing and Development, 126: pp. 341–45.

Slagboom, P.E., M. Beekman, et al. (2011). ‘Genomics of human longevity.’ Philosophical Transactions of the Royal Society: Biological Sciences, 366: pp. 35–42.

Chapter Three
WHY WE AGE

Ageing is not necessary

Malthus’ classic work is available from many publishers:

Malthus, R.T., (first published 1798). An Essay on the Principle of Population. Various publishers.

The essential message of this section is that our lives consist of a phase of programmed development followed by an unprogrammed phase of ageing. One very readable article on this is:

Austad, S.N. (2004). ‘Is aging programed?’ Aging Cell, 3: pp. 249–51.

The ‘disposable soma’

The gerontologist Tom Kirkwood (Newcastle, UK), the spiritual father of the disposable soma theory, has written a very accessible book about his theory:

Kirkwood, T.B. (1999). Time of Our Lives. New York: Oxford University Press

Below are the details of the original publication and a more recent article, in which the theory is applied not only to the question of why we age, but also how:

Kirkwood, T.B. & R. Holliday, (1979). ‘The evolution of ageing and longevity.’ Proceedings of the Royal Society: Biological Sciences, 205: pp. 531–46.

Kirkwood, T.B. (2005). ‘Understanding the odd science of aging.’ Cell, 120: pp. 437–47.

The cost of sex

The unique study by biology professor Bas Zwaan (Wageningen, the Netherlands) was the first successful attempt to collect data by experimenting with fruit flies to prove the disposable soma theory:

Zwaan, B.J., R. Bijlsma, et al. (1995). ‘Direct selection on lifespan in Drosophila melanogaster.’ Evolution, 49: pp. 649–59.

The harmful consequences of sexual reproduction are divided between effects that are a direct result of mating and effects that are indirect, resulting from the fact that there is not one gender, but two, irrespective of whether the act of mating takes place or not. One example of the direct consequences of sexual reproduction in fruit flies is described in detail by the biology professor Linda Partridge (London, UK):

Cordts, R. & L. Partridge (1996). ‘Courtship reduces longevity of male Drosophila melanogaster.’ Animal Behaviour, 52: pp. 269–78.

An example of the consequences for hydras when they undergo sexual metamorphosis — the appearance of ageing — and the role played by stem cells in this phenomenon have been studied and described in detail:

Yoshida, K., T. Fujisawa, et al. (2006). ‘Degeneration after sexual differentiation in hydra and its relevance to the evolution of aging.’ Gene, 385: pp. 64–70.

Nishimiya-Fujisawa, C. & S. Kobayashi (2012). ‘Germline stem cells and sex determination in Hydra.’ International Journal of Developmental Biology, 56: pp. 499–508.

There is a great deal of debate among scientists over the correct explanation for the evolution of sexual reproduction. However, apart from all the argumentation and discussion, evolutionary experiments have also been carried out. They show a changing environment stimulates sexual reproduction, since the necessary investments then outweigh the costs:

Becks, L. & A.F. Agrawal (2010): ‘Higher rates of sex evolve in spatially heterogeneous environments.’ Nature, 468: pp. 89–92.

Aristocratic fruit flies

The following sources relate to the study by Tom Kirkwood and myself of the British nobility:

BBC News. ‘Breed early, die young.’ http://news.bbc.co.uk/2/hi/science/nature/241509.stm

Westendorp, R.G. & T.B. Kirkwood (1998). ‘Human longevity at the cost of reproductive success.’ Nature, 396: pp. 743–46.

Chapter Four
ASSESSORS OF THE FINITE

Insurance premium levels

The anecdote that forms the introduction to this discussion of ‘life-expectancy tables’ — also known as ‘survival analysis’ — is described in more historical detail in the 2010 lecture given by me on the occasion of the anniversary of the founding of Leiden University:

Westendorp, R.G. (2010) ‘Passend of onaangepast? Over de menselijke levensloop in een snel veranderende omgeving.’ [‘Fit or unfit? On human life trajectories in a rapidly changing environment.’] (in Dutch). Leiden University.http://www.leidenuniv.nl/dies2010/dies_2010_oratie.pdf.

There is no consensus among scientists on how to interpret the phenomenon of proportional increase in mortality risks — that is, the Gompertz model. In the past, my colleagues and I have taken a stance on this: that there is a great difference between the doubling of a low risk of mortality and a doubling of a high risk. In the latter case, the additional number of people who die is much greater. This is not only numerically different, but the underlying biological explanations can vary widely. See:

Rozing, M.P. & R.G. Westendorp (2008). ‘Parallel lines: nothing has changed?’ Aging Cell, 7: pp. 924–27.

The impotence of prediction

Sickness and health are fundamentally unpredictable. Doctors are constantly (unpleasantly) faced with the fact that they are unable to make any precise predictions about the long-term development of a disease throughout an individual patient’s life. The article below describes how Ancient Greek physician-philosophers recognised and dealt with this phenomenon:

Ierodiakonou, K. & J.P. Vandenbroucke (1993). ‘Medicine as a stochastic art.’ The Lancet, 341: pp. 542–43.

Chapter Five
SURVIVING IN HARSH CONDITIONS

An extraordinary find in Chad

The references below indicate articles on the paleo-anthropological method, which uses fossil characteristics to make conclusions about the time when the first humans evolved. In this case, the question is when Sahelanthropus is likely to have lived. Current estimates place him 6 to 7 million years ago:

Zollikofer, C.P. & M.S. Ponce de León, et al. (2005). ‘Virtual cranial reconstruction of Sahelanthropus tchadensis.’ Nature, 434: pp. 755–59

An alternative method uses sensitive genetic analyses to estimate the time when the human lineage split from that of chimpanzees and bonobos. According to genetic researchers’ latest calculations, that split began 5.5 million years ago, but was not definitively completed until 3 million years ago. These latest estimates are not in line with those produced by the paleo-anthropological method, and are the subject of debate:

Prüfer, K., K. Munch, et al. (2012). ‘The bonobo genome compared with the chimpanzee and human genomes.’ Nature, 486: pp. 527–31

When the life sciences and medicine are embedded in an evolutionary framework, the genetic basis of disease becomes easier to understand. It offers a logical explanation for why people become increasingly frail due to illness in old age. It replaces the prevailing understanding of organs as separate machines that are robbed of their functionality by specific biological processes. Evolutionary biology is an essential basis for achieving a better understanding of health and disease. See:

Nesse, R.M., C.T. Bergstrom, et al. (2009). ‘Making evolutionary biology a basic science for medicine.’ Proceedings of the National Academy of Science of the USA, 107: pp. 1800–07.

Taking the Leiden University debating tradition as a base, the physician Dr David van Bodegom and I have developed an appealing training method aimed at stimulating students to think in evolutionary terms. Its intention is to encourage them to develop a conceptual framework that will enable them to better understand the ageing process:

Bodegom, D. van, M. Hafkamp, et al. (2013). ‘Using the master-apprentice relationship when teaching medical students academic skills: the Young Excellence Class.’ Medical Science Educator, 23: pp. 80–83.

The book by Richard Dawkins mentioned in this chapter is:

Dawkins, R. (2006) The Selfish Gene — 30th anniversary edition. Oxford, New York: Oxford University Press.

The gold coast of Africa

Between 2002 and 2012, we at the Department of Gerontology and Geriatrics at the Leiden University Medical Centre (LUMC) carried out research in the Garu District of north-eastern Ghana, close to the Togolese border. The study was initiated by the anthropologist Dr Hans Meij, and was later continued by the physician Dr David van Bodegom. Both men wrote their doctoral theses on this research. A whole host of (master’s) students has followed in their footsteps. For the relationship between socio-economic class and mortality, see:

Bodegom, D. van, L. May, et al. (2009). ‘Socio-economic status is highly correlated with mortality risks in rural Africa.’ Transactions of the Society of Tropical Medicine & Hygiene, 103: pp. 795–800.

Taking the human life trajectory — from babyhood to death — as his basic structure, the epidemiologist Professor Tim Spector (London, UK) describes the (evolutionary) hereditary background to personality, physical characteristics, risk of illness, sex, and risk-taking, using case studies of identical and fraternal twins:

Spector, T. (2012). Identically Different: Why You Can Change Your Genes. London: Weidenfeld & Nicolson.

Resistance to infectious disease

When humans began to work the land and keep livestock, many different viruses, bacteria and parasites were presented with new opportunities, resulting in the spread of all kinds of diseases and scourges. This was accompanied by an increase in the number of animal-to-human infections. As human communities grew in size, and the interactions between (groups of) humans became increasingly intensive, diseases that spread without direct contact, such as smallpox, were also able to advance:

Stearns, S.C. & J.C. Koella (Eds.) (2008) Evolution in Health and Disease: Second Edition. Oxford: Oxford University Press

Earlier, the Leiden-based rheumatologist Professor Tom Huizinga and I mimicked human immune reactions in blood samples. This led to ideas about why women who live to a great age have less chance of a successful pregnancy. The article below describes in more detail how the innate immune system increases resistance to infections, while simultaneously increasing the chance that a pregnancy will end preterm in a spontaneous abortion:

Bodegom, D. van, L. May, et al. (2007). ‘Regulation of human life histories: the role of the inflammatory host response.’ Annals of the New York Academy of Sciences, 1100: pp. 84–97.

We were able to demonstrate the phenomenon known to biologists as the ‘quality-quantity trade-off’ among humans:

Meij, L.L., D. van Bodegom, et al. (2009). ‘Quality-quantity trade-off of human offspring under adverse environmental conditions.’ Journal of Evolutionary Biology, 22: pp. 1014–23.

I recommend two references for those who would like to know more about the idea of balancing selection for immune defences. First of all, my colleague Tom Kirkwood and I developed a mathematical model to describe this. Later, we were able to demonstrate the suspected natural-selection mechanism at work on the immune system of subjects in our research area in Ghana:

Drenos, F., R.G. Westendorp, et al. (2006). ‘Trade-off mediated effects on the genetics of human survival caused by increasingly benign living conditions.’ Biogerontology, 7: pp. 287–95.

Kuningas, M., L. May, et al. (2009). ‘Selection for genetic variation inducing pro-inflammatory responses under adverse environmental conditions in a Ghanaian population.’ PLoS One, 4: e7795.

The benefit of grandmothers

I recommend two articles for those who want to explore this broad area of research in more depth. The first concerns the work of the group led by the sociologist Dr Fleur Thomese (Amsterdam), which made use of data from three generations in Dutch families. The second is the work of my own research group on the impact of (grand)parents on the number of children born, and their survival, in Ghana. Both studies were part of a joint research programme financed by the Netherlands Organisation for Scientific Research (NWO) entitled ‘Aging Societies: Human Victory or Evolutionary Trap?’:

Thomese, F. & A.C. Liefbroer (2013). ‘Child care and child births: the role of grandparents in the Netherlands.’ Journal of Marriage and Family, 75: pp. 403–21.

Bodegom, D. van, M. Rozing, et al. (2010). ‘When grandmothers matter.’ Gerontology, 56: pp. 214–16.

Chapter Six
OUR INCREASED LIFE EXPECTANCY

What we used to die of

For a nice overview of John Snow’s original work and the impact it had on the theory and practice of medicine, see:

Fine, P., C.G. Victora, et al. (2013). ‘John Snow’s legacy: epidemiology without borders.’ The Lancet, 381: pp. 1302–11.

The first description of epidemiological transition is discussed in:

Omran, A.R. (reprint, first published in 1971) (2005) ‘The epidemiologic transition: a theory of the epidemiology of population change.’ The Milbank Quarterly, 83: pp. 731–57

On the decline of violence in the world, see:

Pinker, S. (2011). The Better Angels of Our Nature: a history of violence and humanity. London: Penguin Books.

The new killers

A good recent study of the causes of death of mummified humans, showing that cardiovascular disease also occurred in antiquity, is:

Thompson, R.C., A.H. Allam, et al. (2013). ‘Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.’ The Lancet, 381: pp. 1211–22.

More than three-quarters of the world’s cases of chronic degenerative disease occur in low-income or middle-income countries. Risk factors that are associated with affluence, such as high blood pressure, high cholesterol levels, and too little exercise play an ever-increasing role in the pattern of disease in such countries. See:

World Health Organization (2009). Global Health Risks: mortality and burden of disease attributable to selected major risks. Geneva: WHO Press.

In order to better understand the explosion of diabetes in cities — urban diabetes — public and private partners have joined forces and are currently mapping the urban-diabetes challenges in a number of cities across the world. The aim is to generate a body of collective knowledge about what is working today, where the challenges are, and what the priorities should be for the future:

http://citieschangingdiabetes.com/

A revolution in medical technology

For an overview of everything possible in the area of cardiovascular disease, I recommend the following websites:

http://www.heartfoundation.org.au

http://www.bhf.org.uk

http://www.heart.org.

On the early signs of atherosclerosis among fallen American servicemen:

Webber, B.J., P.G. Seguin, et al. (2012) ‘Prevalence of and risk factors for autopsy-determined atherosclerosis among US service members, 2001–2011.’ Journal of the American Medical Association, 308: pp. 2577–83.

An extra weekend every week

The internationally renowned Max Planck Institute for Demographic Research (MPIDR, Rostock, Germany), under the leadership of the demographer Professor Jim Vaupel, carries out research on our increasing life expectancy, also from an evolutionary biology perspective. Jim Vaupel has developed a realistic scenario for the permanent increase in life expectancy. For an analysis and a projection of the increase in our life expectancy, see:

Oeppen, J. & J.W. Vaupel (2002). ‘Demography. Broken limits to life expectancy.’ Science, 296: pp. 1029–31.

Vaupel, J. W. (2010). ‘Biodemography of human aging.’ Nature. 464: pp. 536–42

The extrapolation of increasing life expectancy caused a veritable storm of public controversy. For instance, see:

http://www.theatlantic.com/features/archive/2014/09/why-i-hope-to-die-at-75/379329/

As another example of this relentless rise, the Australian government’s 2015 Intergenerational Report projects that in 2054–55, life expectancy for Australians at birth will be 95.1 years for men and 96.6 years for women. (In 2015, the figures were 91.5 years for men and 93.6 for women.) The report also predicts that by 2054–55 nearly 2 million Australians will be aged 85 and over, of which approximately 40,000 will be over 100 years old.

To read more of this report, go to: http://www.treasury.gov.au/PublicationsAndMedia/Publications/2015/2015-Intergenerational-Report

Chapter Seven
LEGIONS OF THE OLD

The gravedigger

Data on age at death from the nineteenth century onwards can be found on the website of Statistics Netherlands. An alternative source of information is the Human Mortality Database, which is maintained by the Max Planck Institute for Demographic Research (MPIDR). A graphic representation of the number of deaths per age group over time can be found on the website of the Leyden Academy on Vitality and Ageing. The gravedigger’s story is based on this data. For graphic representations, see:

http://www.leydenacademy.nl/Ageing/What_can_be_learned_from_gravediggers

The Lochem gravedigger Lenderink was a real person. His annual report from 1889 is part of Dutch cultural history:

Spruit, R. (1986). De dood onder ogen: een cultuurgeschiedenis van sterven, begraven, cremeren en rouw [Facing Death: a cultural history of death, burial, cremation and mourning]. (in Dutch) Houten: De Haan.

From pyramid to skyscraper

For a theoretical consideration of democratic transition — the change in the structure of the population due to a shift in the causes of death — see:

Galor, O. & D.N. Weil (2002). ‘Population, technology, and growth: from Malthusian stagnation to the demographic transition and beyond.’ The American Economic Review, 90: pp. 806–28.

For the concept of the second demographic transition — the change in fertility patterns due to reduced mortality — see:

Kaa, D.J. van de (1987) ‘Europe’s second demographic transition.’ Population Bulletin, 42: pp. 1–59.

For a description of the demographic transition as observed by my research group in our study area in Ghana, see:

Meij, L.L., A.J. de Craen, et al. (2009). ‘Low-cost interventions accelerate epidemiological transition in Upper East Ghana.’ Transactions of the Royal Society of Tropical Medicine and Hygiene, 103: pp. 173–78.

Young and old-age dependency ratios

For more on the development of demographic ratios in the Netherlands, I recommend the websites of Statistics Netherlands (the Dutch national statistics office) and the Netherlands Interdisciplinary Demographic Institute (NIDI). For data on young- and old-age dependency ratios for countries in the world — past, present, and future trajectories — see population statistics of the United Nations at:

http://esa.un.org/unpd/ppp/Figures-Output/Population/PPP_Total-Dependency-Ratio.htm

Please note that, in this book, I have followed the age categories of Statistics Netherlands, which employs a higher cut-off for defining young people (below 20 years) than the United Nations (below 15 years). This explains the disparities with the numbers on the UN site (the young-age dependency ratios are higher in my text). In a same vein, some statistical offices use a cut-off of 60 years to define older people, which has the effect of increasing the old-age dependency ratios even further. Decisions on these cut-off points have considerable socio-economic impact, and are thus the subject of intense political debate. Irrespective of the specific cut-offs, the trends over time will not be different.

A fantastic tool for creating your own analyses, graphics, and diagrams can be found at:

Gapminder: http://www.gapminder.org

For the costs of raising kids in Australia, see:

NATSEM at the University of Canberra. The cost of raising children in Australia. AMP.NATSEM Income and Wealth Report issue 33, May 2013.

Chapter Eight
AGEING IS A DISEASE

What causes cancer?

For an overview of the relation between ageing and cancer, I recommend the work of the molecular biologist Professor Jan Hoeijmakers (Rotterdam), a researcher of international repute in the field of DNA damage, the pathogenesis of cancer, and ageing:

Hoeijmakers, J.H. (2009). ‘DNA damage, aging, and cancer.’ New England Journal of Medicine, 361: pp. 1475–85.

The occurrence of random mutations that arise during DNA replication in normal, non-cancerous stem cells is related to the risk of cancer. The difference in stem-cell divisions may explain the huge differences in the various types of cancer. This could also explain the element of ‘bad luck’ — that is, the impotence of prediction. See:

Tomasetti, C. & B. Vogelstein (2015) ‘Variation in cancer risk among tissues can be explained by the number of stem cell divisions,’ Science, 347: pp. 78–81.

Normal ageing does not exist

There is no difference between ageing and the development of disease in old age. I demonstrate this in two stages. The first stage is based on the theory of the origin of disease developed by the epidemiologist Professor Kenneth Rothman (Boston, USA). Disease does not have just one cause, but always results from the interplay of partial causes, which themselves are not sufficient to explain the genesis of disease alone. In this book, I explain this using the example of the Concorde disaster. Rothman’s original 1976 publication in the American Journal of Epidemiology is the best, in my opinion, because it presents the facts in a plain and simple way. This model of pathogenesis has been revised and adapted many times. For the most recent version, see:

Rothman, K.J. & S. Greenland (2004). ‘Causation and causal inference in epidemiology.’ American Journal of Public Health, 95: pp. 144–50.

In the second stage of my argument, I apply the theory of partial causes of disease to the principle of ageing as explained by the accumulation of small forms of damage that come together to explain a disease or impairment. I have tried to explain this in this book using the game of bingo as an analogy. See:

Izaks, G.J. & R.G. Westendorp (2003). ‘Ill or just old? Towards a conceptual framework for the relation between ageing and disease.’ BMC Geriatrics, 3: e7.

Wensink, M., R.G. Westendorp, et al (2014). ‘The causal pie model: an epidemiological method applied to evolutionary biology and ecology.’ Ecology and Evolution, 4:1924–30.

The dementia epidemic

For a reference to the stirring neuropathological study that has been dubbed ‘The Nun Study’, see:

Snowdon, D. Aging with Grace (2001). New York: Bantam Books.

Predicting the number of dementia patients in the near and distant future is part of a public debate on the subject. I take the view that the end of the dementia epidemic is in sight. I base this opinion on the knowledge that dementia in old people has a multi-causal explanation and that its various partial causes can be influenced effectively. See:

Savva, G.M., S.B. Wharton, et al. (2009). ‘Age, neuropathology, and dementia.’ The New England Journal of Medicine, 360: pp. 2302–09.

Since research shows that cardiovascular disease plays a large role in the cause of dementia — and the prevalence of cardiovascular disease has fallen drastically in the past — the risk of developing dementia must have shrunk in the past ten to twenty years. Various studies were published in the course of 2012–2013 that include figures to support this interpretation:

Schrijvers, E.M., B.F. Verhaaren, et al. (2012). ‘Is dementia incidence declining? Trends in dementia incidence since 1990 in the Rotterdam Study.’ Neurology, 78: pp. 1456–63.

Qiu, C., E. von Strauss, et al. (2013). Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden.’ Neurology, 80: pp. 1888–94.

Christensen, K., M. Thinggaard, et al. (2013). ‘Physical and cognitive functioning in people older than 90 years: a comparison of two Danish cohorts born 10 years apart.’ The Lancet, 382: pp. 1507–13.

Matthews, F.F., A. Arthur, et al. (2013). ‘A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the cognitive function and ageing study I and II.’ The Lancet, 382: pp. 1405–12.

Frailty

Although the principle of frailty is easy to define, it is difficult to estimate an individual person’s degree of frailty, just as the course of a disease or the event of death is difficult to predict. This difficulty is reflected in the fact that so many definitions of frailty have been put forward. The geriatrician Professor Marcel Olde Rikkert (Nijmegen, the Netherlands) has shown before that — disturbingly — some people are sometimes declared to be frail and sometimes not, depending on the definition used. There is currently no gold standard:

Iersel, M.B. van, & M.G. Rikkert (2006). ‘Frailty criteria give heterogeneous results when applied in clinical practice.’ Journal of the American Geriatric Society 54: pp. 728–29.

It is not possible to predict frailty, illness, and death for individuals, but it can be done for groups. A simple and decisive measure is walking speed:

Studenski, S., S. Perera, et al. (2011). ‘Gait speed and survival in older adults.’ Journal of the American Medical Association, 305: pp. 50–58.

Chapter Nine
THE BIOLOGY OF AGEING

For more background information on the biology of ageing, I recommend the website of the National Institute of Aging (Bethesda, USA)

http://www.nia.nih.gov/health/publication/biology-aging.

For those who would like to read more about proximate and ultimate causation, I recommend the work of the Ukrainian-American geneticist Theodosius Dobzhansky (1900–1975). He was one of the most important proponents of ‘modern evolutionary synthesis’, which unites genetics — in particular, Mendel’s laws — with evolutionary theory.

Dobzhansky, T. (1973). ‘Nothing in biology makes sense except in the light of evolution.’ The American Biology Teacher, 35: pp. 125–29.

As part of an experiment for his master’s students, the behavioural biologist Professor Carel ten Cate (Leiden) replicated the fieldwork of the Dutch behavioural biologist Niko Tinbergen (1907–1988):

Cate, C. ten, W. Bruins, et al. (2009). ‘Tinbergen revisited: a replication and extension of experiments on the beak colour preferences of herring gull chicks.’ Animal Behaviour, 77: pp. 795–802.

Accelerated ageing

One of the most eminent scientists who put ‘progeroid syndromes’ on the map is the pathologist Professor George Martin (Washington, USA). In the article recommended below, he discusses the various syndromes, and indicates how they differ from the usual human ageing process:

Martin, G.M. (2005). ‘Genetic modulation of senescent phenotypes in Homo sapiens.’ Cell, 120: pp. 523–32.

Oxygen radicals

Professor Gems (London, UK), a molecular biologist, has carried out some unique experiments in which he used genetic manipulation to switch off the natural antioxidant mechanisms gradually in nematode worms and fruit flies. This had no impact on their survival rate. For a critical discussion of the ‘oxygen radical theory of ageing’, see:

Gems, D. & R. Doonen (2009). ‘Antioxidant defence and aging in C. elegans: is the oxidative damage theory of aging wrong?’ Cell Cycle, 8: pp. 1681–87.

Researchers have gathered data on a total of 296,707 people who took part in various experimental studies on the effect of supplements containing antioxidants. The conclusion is that such supplements have no beneficial effect:

Bjelakovic, G., D. Nikolova, et al. (2012). ‘Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.’ The Cochrane Library, 14 March.

Insulin and growth hormone

The idea that humans have evolved to be economical with energy — known as the ‘thrifty gene hypothesis’ — was first developed by the American geneticist James Neel (1915–2000), who wanted to find a plausible explanation for the increasing prevalence of diabetes in our modern environment. This theory may also explain why people quickly become obese during times of abundance. The following article deals with the original theory:

Neel, J.V. (1962). ‘Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by “progress”?’ The American Journal of Human Genetics, 14: pp. 353–62.

The theory is controversial. Some scientists have formulated opposing theories, in which they argue that there was selective pressure against obesity in our original environment, since an athletic constitution was advantageous in an environment where humans could be preyed on by other species:

Speakman, J.R. (2007). ‘A nonadaptive scenario explaining the genetic predisposition to obesity: the “predation release” hypothesis.’ Cell Metabolism, 6: pp. 5–12.

Researchers believe that the activity of genes is adapted for optimal metabolism in the circumstance in which an individual finds itself. Thus, circumstances in the womb should be able to induce life-long changes in an individual’s genetic material. This is called ‘epigenetics’. For example, it is thought that the metabolism of children carried during the Dutch Winter Famine of 1944 is more ‘thrifty’ than others’. The epidemiologist Dr Tessa Rosenboom (Amsterdam) has written a wonderful book on this subject:

Rosenboom, T. & R. van de Krol (2010). Baby’s van de Hongerwinter: de onvermoede erfenis van ondervoeding [Babies of the Winter Famine: the unexpected legacy of malnutrition] (in Dutch). Amsterdam: Augustus.

Professor David Barker (Southampton, UK) is the original advocate of the theory that may explain why children of the Winter Famine have higher incidences of obesity and cardiovascular disease. See:

Hales, C.N. & D.J. Barker (1992). ‘Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis.’ Diabetologia, 35: pp. 595–601.

The biologist Professor Eline Slagboom (Leiden) and her colleagues were the first to show that the genes of those who survived the Winter Famine are calibrated differently to their siblings who did not survive:

Heijmans, B.T., E.W. Tobi, et al. (2008). ‘Persistent epigenetic differences associated with prenatal exposure to famine in humans.’ Proceedings of the National Academy of Sciences of the United States of America, 105: pp. 17046–17049.

The following are two articles on the Leiden 85-plus Study and the Leiden Longevity Study, in which we tested whether variations in the insulin/IGF-1 signalling pathway can explain differences in longevity:

Heemst, D van, M. Beekman, et al. (2005). ‘Reduced insulin/IGF-1 signaling and human longevity.’ Aging Cell, 4: pp. 79–85.

Rozing, M.P., R.G. Westendorp, et al. (2009). ‘Human insulin/IGF-1 and familial longevity at middle age.’ Aging (Albany, NY), 1: pp. 714–722.

The article recommended below is an overview for advanced readers which covers the connection between insulin/IGF-1 signalling pathway, environment, selection, adaptation, growth, metabolism, and lifespan:

Gems, D. & L. Partridge (2013). ‘Genetics of longevity in model organism: debates and paradigm shifts.’ Annual Review of Physiology, 75: pp. 621–644.

Should we eat less?

Many books have been written about ‘caloric restriction’, and entire movements have been based on the theory. Caloric restriction is erroneously seen as the Holy Grail that can slow the pace of ageing under any circumstances. In mice, its life-prolonging effect appears to be strongly dependent on the animals’ genetic background, and it is not possible to produce a beneficial effect in all species and in all individual members of a species:

Liao, C.Y., B.A. Rikke, et al. (2010). ‘Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening.’ Aging Cell, 9: pp. 92–95.

The next question is whether caloric restriction works in humans. It is not easy to find this out by experimental means. That would require subjects who are willing to subject themselves to a normal or restricted caloric intake for their entire lives. Nevertheless, preparations are underway for a long-term experiment of this kind. For those who are interested:

Caloric restriction in humans: http://calerie.dcri.duke.edu/

Finally, I recommend two recent publications concerning two long-term experiments with caloric restriction in rhesus monkeys in the United States. The preliminary conclusion is that some obesity-related diseases, such as diabetes, do not occur in the calorie-restricted group. A beneficial influence on lifespan has not (yet) been demonstrated:

Colman, R.J., R.M. Anderson, et al. (2009). ‘Caloric restriction delays disease onset and mortality in rhesus monkeys.’ Science, 325: pp. 201–204.

Mattison, J.A., G.S. Roth, et al. (2012). ‘Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study.’ Nature, 489: pp. 318–321.

Chapter Ten
LONG MAY WE LIVE

More years of illness

For a definition of and figures on healthy life expectancy, I recommend the National Public Health Compass provided by the Dutch National Institute for Public Health and the Environment, as well as the Dutch national statistical bureau, Statistics Netherlands. Trends in (healthy) life expectancy in the Netherlands over the past 30 years are described in:

Engelaer, F.M., D. van Bodegom, et al. (2013). ‘Sex differences in healthy life expectancy in the Netherlands.’ Annual Review of Gerontology and Geriatrics, 33: pp. 361–371 (11).

More years without impairment

Screening and preventive measures are often introduced without knowing whether any resultant intervention will lead to a predetermined health effect. Often, we lack the tools to identify the right individuals, or no effective intervention is available anyway. In the latter case, there is simply no reason for screening people. The expert panel mentioned in the text, which systematically evaluated the arguments for and against screening, published an article on its assessments:

Drewes, Y.M., J. Gussekloo, et al. (2012). ‘Assessment of appropriateness of screening community-dwelling older people to prevent functional decline. Journal of the American Geriatric Society, 60: pp. 42–50.

There is controversy surrounding the lowering of the upper age-limit for breast-cancer screening, although it was the result of careful consideration on the part of the Health Council of the Netherlands: ‘A model calculation by the National Evaluation Team for Breast Cancer Screening (LETB) determined that the beneficial effects of screening for breast cancer outweigh the negative effects, up to the age of 75.’ On the basis of this, a court in The Hague ruled on 9 February 2010 that an age limit of 75 can be applied in breast-cancer screening. The ruling concerned an appeal against the Dutch State brought by three women, the Clara Wichmann Test Case Fund Foundation, and the Netherlands Breast Cancer Association.

Gezondheidsraad: Commissie WBO (2001). Wet bevolkingsonderzoek: landelijke borstkanker-screening (2). [Health Council of the Netherlands: Commission on the Population Screening Act (WBO) (2001). Population Screening Act: national breast cancer screening (2).] (in Dutch). The Hague: publication no. 2001/2.

The ragged end

Ideas about healthy ageing go back to the (false) claim by the American doctor James Fries that in the future we will be able to remain healthy to the last moment — thanks to our ability to eliminate disease — and then die between the ages of 70 and 90 due to the mechanism of ageing:

Fries, J.F. (1980). ‘Aging, natural death, and the compression of morbidity.’ The New England Journal of Medicine, 303: pp. 130.135.

The demographer Professor John Wilmoth (Berkeley, USA) uses data from Sweden and Japan from the past fifty years to demonstrate that this simply does not happen. In doing so, he also shows that it is never likely to happen, because it is not only the age at death that is rising, but also the maximum age reached. This means that all deaths are shifted to later in life, and that is precisely what was demonstrated in the genetic experiments carried out with nematode worms:

Wilmoth, J.R., & S. Horiuchi (1999). ‘Rectangularization revisited: variability of age at death within human populations.’ Demography, 36: pp. 475–495.

Wilmoth, J.R., L.J. Deegan, et al. (2000). ‘Increase of maximum life-span in Sweden, 1861–1999.’ Science, 289: pp. 2366–2368.

Kirkwood, T.B., & C.E. Finch (2002). ‘Ageing: the old worm turns more slowly.’ Nature, 419: pp. 794–795.

Chapter Eleven
THE QUALITY OF OUR EXISTENCE

What is healthy?

For more information on the World Health Organization (WHO) definition of health, see: http://www.who.int/about/definition/en.

For the ‘disability paradox’, see:

Albrecht, G.L. & P.J. Devlieger (1999). ‘The disability paradox: high quality of life against all odds.’ Social Sciences & Medicine, 48: pp. 977–988.

Convinsky, K.E., A.W. Wu, et al. (1999). ‘Health status versus quality of life in older patients: does the distinction matter?’ The American Journal of Medicine, 106: pp. 435–440.

The Leiden 85-plus study

In 1997, Annetje Bootsma, Eric van Exel, Margaret von Faber, Jacobijn Gussekloo, Dr Gooke Lagaay, the late Professor Dick Knook, and I took a random sample of the people of Leiden. All 599 85-year-olds were visited over a period of two years and monitored over a period of more than ten years for health, illness, quality of life, and death. This interdisciplinary cooperation between doctors and gerontologists from Leiden and the Amsterdam-based cultural anthropologists the late Dr Els van Dongen and Professor Sjaak van der Geest delivered a number of new and enriching insights. The study into being healthy and feeling healthy as described in this book is a core publication from that period:

Faber, M. von, A. Bootsma-van der Wiel, et al. (2001). ‘Successful aging in the oldest old: who can be characterized as successfully aged?’ JAMA International Medicine, 161: pp. 2694–2700.

In this partial study, two classic, mutually exclusive interpretations of successful ageing were tested among 85-year-olds. For the original articles in which these theories were presented, see:

Rowe, J.W. & R.L. Kahn (1987). ‘Human aging: usual and successful.’ Science. 237: pp. 143–149.

Baltes, P.B. & B.M. Baltes (1990). ‘Psychological perspectives on successful aging: the model of selective optimization with compensation.’ In: Baltes, P.B & B.M. Baltes (Eds.) (1990). Successful Ageing: Perspectives from the Behavioural Sciences, pp. 1–34. Cambridge: The Press Syndicate of the University of Cambridge.

A rating for life

The sociologist Professor Ruut Veenhoven (Rotterdam) investigates the social conditions that contribute to human happiness. He does this by asking people one single question about their lives: ‘How satisfied are you, all things considered, with the life you lead?’ The basis for his research is described here:

Veenhoven, R. (2000). ‘The four qualities of life.’ In: McGillivray, M. & M. Clarke (Eds.) (2006). Understanding Human Well-Being, pp. 74–100. New York: United Nations University Press.

Measuring feelings can be very subjective, but is nonetheless a useful complement to more objective data when comparing quality of life across countries. Subjective data can provide a personal evaluation of an individual’s health, education, income, personal fulfilment, and social conditions. For a more elaborate discussion of the topic, see:

WHO (2013) World Happiness Report. New York, WHO.

For the report of the Commission on Wellbeing and Policy, see:

O’Donnell, G., Deaton, A., et al. (2014). Wellbeing and Policy. London: Legatum Institute.

When asked to rate their general satisfaction with life on a scale from 0 to 10, people across the OECD gave it a 6.6 grade. Life satisfaction is not evenly shared across the OECD, however. See:

http://www.oecdbetterlifeindex.org/topics/life-satisfaction/

Life satisfaction levels fall only in the final year of life, which is unsurprising in view of the fact that death is usually preceded by increasing infirmity. This effect has been demonstrated in follow-up studies in several developed countries:

Gerstorf, D., M. Hidajat, et al. (2010). ‘Late-life decline in well-being across adulthood in Germany, the United Kingdom, and the United States: something is seriously wrong at the end of life.’ Psychology and Aging, 25: pp. 477–85.

Chapter Twelve
VITALITY

The new ‘Ages of Man and Woman’

As a concept, the new ‘Ages of Man and Woman’ consist of stages of prevention, multimorbidity, frailty, and dependency. My colleague Marieke van der Waal and I first published this idea in:

Westendorp, R.G. & M. van der Waal (2011). ‘Anders kijken naar de ouderenzorg.’ [‘Taking a different view of old-age care.’] (in Dutch). Zorgmarkt, 11: pp. 13–16.

The staggering finding that we in the West fail to treat, or treat adequately, three-quarters of cases of high blood pressure — an important risk factor for dementia in old age — can be found in:

Chow, C.K., K.K. Teo, et al. (2013). ‘Prevalence, awareness, treatment and control of hypertension in rural and urban communities in high-, middle-, and low-income countries.’ Journal of the American Medical Association, 310: pp. 959–68.

Support for the statement ‘it is better to smoke than have a small social network’ can be found in:

Holt-Lunstad, J., T.B. Smith, et al. (2010). ‘Social relationships and mortality risks: a meta-analytic review.’ PLoS Medicine 7, e1000316.

The present design of the healthcare system is associated with major problems in the treatment of various currently occurring complaints. An initial orientation in this subject matter can be found in:

Boyd, C.M., J. Darer, et al. (2005). ‘Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay and performance.’ Journal of the American Medical Association, 294: pp. 716–24.

More than 60 per cent of doctors in the Netherlands believe that seriously ill patients in the final stages of life are treated for longer than desirable; 22 per cent disagree. The rest indicated no opinion.

Visser, J. (2012). ‘De arts staat in behandelmodus.’ [‘The doctor is in treatment mode’] (in Dutch). Medisch Contact, 22: pp. 1326–29.

The view is vocally expressed by the US-based surgeon and popular author Dr Atul Gawande. See:

Gawande, A. (2014). Being Mortal: illness, medicine and what matters in the end. London: Profile Books.

In this book, I argue that professionals in long-term care are often caught in a medical, technical, and legal way of thinking, while not listening enough to the people they are treating. As justification of this bold statement, I present here the example of under-nutrition.

Under-nutrition is regarded as a medial alarm signal in the care of old people. For this reason, the various professions have developed guidelines to identify and treat under-nutrition in old people. The incidence of under-nutrition is also seen as a quality indicator of (medical) care. For this reason, institutions work according to protocols, and public-health inspections check them for compliance. All these actions are highly remarkable, since the Health Council of the Netherlands has determined that under-nutrition cannot be unambiguously defined, its cause cannot generally be well identified, and general guidelines to identify and treat it cannot be drawn up:

Health Council of the Netherlands (2011). Undernutrition in the Elderly. The Hague, Health Council of the Netherlands 2011/32E

Thus, under-nutrition is an example of my claim that in nursing and care homes we often miss the point, and professionals are too rarely in a position to provide for the wishes of patients. Under-nourishment needs to be approached in a completely different way. Wija van Staveren (Wageningen, the Netherlands), Professor of Nutrition and the Elderly, has shown that setting the table, serving food in tureens, and allowing residents time to eat at their own pace can turn the trend of weight loss in institutions into a trend of weight gain:

Nijs, K.A., C. de Graaf, et al. (2006). ‘Effect of family-style mealtimes on quality of life, physical performance, and body weight of nursing home residents: cluster randomised controlled trial.’ British Medical Journal, 322: pp. 1180–84.

Optimism and zest for life

Social scientists have long stressed that vitality plays an important part in wellbeing in old age. Vitality is characterised by features such as introspection, positive emotions, energy, involvement, resilience, self-confidence, independence, and a sense of purpose. See:

Ryan, R.M. & C. Frederick (1997). ‘On energy, personality, and health: subjective vitality as a dynamic reflection of well-being.’ Journal of Personality, 65: pp. 529–65.

In the context of ageing, the Leyden Academy on Vitality and Ageing has created an operating definition of vitality: the ability of a person to set ambitions that are appropriate for their life situation, and to realise those goals despite functional limitations. The importance of achieving individual goals for a sense of wellbeing has often been stressed and is essential in old age when ambitions and goals are seen as less than obvious:

Westendorp, R.G., B. Mulder, et al. ‘When vitality meets longevity. New strategies for health in later life.’ In: Kirkwood, T.B. & C.L. Cooper (Eds.) (2013). Wellbeing in Later Life: a complete reference guide, Volume IV: Wellbeing in Later Life. London: John Wiley & Sons, Ltd.

For a reference to the revolution in thinking that took place in cultural anthropology, see:

Marcus, L. & A. Marcus (1988). ‘From soma to psyche: the crucial connection. Part 2. Cross-cultural medicine, decoded: learning about “us” in the act of learning about “them”. Family Medicine, 20: pp. 449–57.

Grey is not black and white

Medical Delta, a partnership between the universities of Leiden, Delft, and Rotterdam and the South-Holland provincial government, applies its members’ knowledge and expertise to finding solutions to the social and personal consequences of the ageing society. These activities are bundled in the VITALITY! Programme. The research project, Many Shades of Grey: ambitions of 55+, paints a picture of the views, desires, and needs of old people as they seen by themselves. The questions and answers are presented from a representative sample of 650 people aged 55 or older. The questions were developed in a preparatory study with panels of older people. See: http://www.leydenacademy.nl/UserFiles/file/Report_Shades_of_grey_LR.pdf.

Chapter Thirteen
THE NEW LIFE TRAJECTORY

75 Is the new 65

In his farewell lecture, the sociologist Professor Kees Knipscheer (Amsterdam) argued for over-50s to begin thinking of ending their first career and starting a second one. The second career would ideally be more focussed on acquired expertise, and should not be allowed to degenerate into a form of early retirement. A second career can be more flexible, whether it involves part-time working or not. Over-50s may work as self-employed entrepreneurs or as employees with a variable pay system. The social-security system should be integrated with the already-initiated changes to the laws regulating retirement and pre-retirement:

Knipscheer, K. (2005). De uitdaging van de tweede adolescentie. [The Challenge of the Second Adolescence.] (in Dutch). Amsterdam: Oratie Vrije Universiteit.

Who is responsible for what?

The original version of Martina Rosenberg’s book Mother, When Will You Finally Die?:

Rosenberg, M. (2013) Mutter, wann stirbst du endlich? (in German). Munich. Blanvalet Verlag.

A birthday rhyme

Figures concerning remaining life expectancy can be found on the website of Statistics Netherlands. For an interpretation of those statistics, see:

Hintum, M. van (2013). ‘Nog nooit zo lang gezond’. [‘Healthy Longer than Ever’] (in Dutch). De Volkskrant, 2 March 2013.

A PRESCRIPTION FOR THE FUTURE

My interpretation of current dietary advice does not differ significantly from that of Professor Walter Willett (Harvard, USA), the world’s most-cited professor of nutrition, as they are presented in his bestseller:

Willett, W.C. (2005). Eat, Drink, and Be Healthy: the Harvard Medical School guide to healthy eating. New York: Free Press.

John Ioannides, Professor of Epidemiology (Stanford, USA), is even more direct, pointing out that research results into eating habits are often ‘too good to be true’.

Ioannides, J.P. (2013). ‘Implausible results in human nutrition research.’ BMJ, 347: p. 6698

One Dutch advocate of behavioural change as a guiding principle for new public health is Willem van Mechelen (Amsterdam, the Netherlands), Professor of Public and Occupational Health. He has written on the subject, in collaboration with colleagues, in:

Matheson, G.O., M. Klügl, et al. (2013). ‘Prevention and Management of Non-Communicable Disease: the IOC Consensus Statement, Lausanne 2013.’ British Journal of Sports Medicine, 47: pp. 1003–11.

Increasing frail older people’s own strength, listening to them, and introducing professional action on the basis of what they say is the central principle of the Dutch National Care for the Elderly Programme:

http://www.nationaalprogrammaouderenzorg.nl/english/the-national-care-for-the-elderly-programme/