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THE RHYTHM OF LIFE

Everything that exists, ages. That’s true of books, beer glasses, washing machines, and people. Ageing, as a process, is the result of an accumulation of minute amounts of damage that we incur simply by being. From a biological and evolutionary point of view, there is no reason for us to get old. It is our early lives that count: when we have the capacity to conceive, bear, and raise children. When that is done, our useful life is over, in the biological sense. Our chronological age, health, and social standing are bound up together by the ageing process. Developments in technology and medicine mean that our biological and chronological age are becoming increasingly disconnected from each other.

Some time ago, I was invited to speak about ageing at an event organised by a debating society that meets once a year to discuss a matter of importance. The club went back a long way, and its members were also no longer in the bloom of youth, so to speak, so the subject was close to their hearts. They wanted me to shed some light on it for them.

I was given free rein to give my talk in any way I pleased; but, free or not, it is never an easy task to explain the central concepts of the ageing process to a general audience. I myself only really gained a clear idea of them a few years ago. I wanted somehow to show those people in the audience, by means of an example taken from their own experience, that ageing is a universal phenomenon — not only among humans, but all material, living or not. That would make for an interesting discussion. Perusing my bookshelves, I found an old copy of the Bible — leather bound, published in 1856. Bookworms had left it riddled with holes. I took the volume from the shelf and opened it. Several pages fell out of it as I turned them. No matter how careful I was, the leaves turned to dust beneath my fingers. The book had aged; it was now old, very old.

The story of the disintegrating Bible left a great impression on the members of that society. Just as the book had become fragile, they could feel in their very bones that their bodies had become frail. It was a revelation when they began to appreciate that everything ages. Then I pointed out that there is one part of the Bible that does not age: its contents. They are read, recited, sung, and reprinted over and over again. The text remains as alive as it ever was.

AN ACCUMULATION OF DAMAGE

It might seem glib to equate old people with old books, but the comparison is a valid one. I first came upon it after learning about the work of the Nobel Prize laureate Peter Medawar. It was then, in Manchester, England in 1998, that I first began to wonder why we age.

My generation of doctors, who studied in the nineteen-seventies and eighties, were only taught about the difference between children and adults. No further variety in human age was recognised by science back then. Ageing received little more than a passing mention. It was not until much later, when I was in Manchester, that I learned about the principles behind the ageing process, and began to understand them. Interestingly, to do so I had to abandon the mantle of the medical scientist, and to assume that of the biologist. Biologists seek to explain the diversity among different species and their different lifecycles — development, reproduction, and eventual demise — under very diverse circumstances. For this reason, biologists spend a lot of time thinking about ageing, and the field boasts a whole host of great thinkers about that issue, beginning with Charles Darwin. It is quite remarkable that so little of this rich trove of biological knowledge and thought has found its way into medical science; all the more so because the majority of those seeking the help of doctors these days are old people.

In Manchester, far from any patient’s bedside, and in the midst of a biological research group working with worms and flies, I had the time to think about the ageing process. Why do functions inevitably decline? One of the classic thinkers I met, on paper, at least, was Peter Medawar. He received a Nobel Prize for his work in a completely different field — that of kidney transplantation. At the opening of his laboratory in 1951, he made a speech entitled ‘An Unsolved Problem of Biology’, an initial attempt to understand why we age. Even today, it is a pleasure to read that speech. At Leiden, we use his work to introduce medical students to our ‘Ageing’ course.

Medawar’s text is striking in its use of plain words to explain the fact that ageing is a ubiquitous process. His comparison between glasses and human beings completely changed my perspective. When a bartender goes to pull a pint of beer but accidentally knocks the glass against the bar as he reaches for the tap, the glass will sometimes break. It may be a new glass that shatters. In that case, there must have been some tension in it due to an irregularity that arose during the moulding or blowing process — a manufacturing fault. But the vast majority of glasses that get broken in this way are simply old, and are liable to shatter at the slightest impact. A ‘young’ glass reacts with a resounding ring when it is knocked against the bar: the shock is absorbed by the material it is made of. But it is a very different story with an old glass, which reacts with a dull crack, and breaks. We call this ‘material fatigue’, an accumulation of tiny amounts of structural damage. An old glass may still look fine, but will break on the slightest of impacts — just like an old rubber band that snaps when stretched.

As with books and glasses, washing machines also break down with time — not because of any manufacturing defect, but due to wear and tear, the damage suffered by the machine over the years, which makes it liable to break even at normal, moderate levels of use. Such an appliance is simply old, and is usually replaced.

Because manufacturers know the rate at which their products age, they can estimate precisely how long the machine will last. The main factor influencing the appliance’s useful life expectancy is the choice of materials and technology used to make it. So there is little element of chance involved when the machine ‘suddenly gives up the ghost’ and ‘falls apart’, requiring the purchase of a new one. After all, they’re deliberately designed to do that. You can even find tables on the Internet listing how many washing cycles that various models are designed to survive.

Realising that all lifeless matter ages is an essential step toward understanding the human ageing process. We do not age by living, but simply by ‘being’. This is a universal principle. Books, beer glasses, rubber bands, and washing machines age, even if they are never used. As time passes, damage accumulates in the materials they are made of, making them liable to fall apart under the slightest pressure. This is no different from the damage that occurs to the tissues that living organisms are made of, causing people to become ill and frail, and to eventually die. A general definition of ageing could be that, over the years, something or someone becomes increasingly fragile or delicate, and breaks or dies when exposed to even slight stress. This leads directly to the negative connotations many associate with ageing: ‘See! It’s all downhill from here.’

ALL FOR THE NEXT GENERATION

Once we turn 50, it becomes inescapably clear: our bodies demand more attention. Our bodies used to be able to get back on track easily after a bout of exertion, but when we reach that age, a day working in the garden can take some recovering from. The next morning, we find our arms, back, and legs sending us some very unmistakeable messages. Our bodies need time and rest to repair the damage done to our muscles and joints, possibly even with the help of massage or medication. The first time it happens, we suffer this discomfort with a certain equanimity. We reason that anyone who does a bit of sport or gardening can sustain an injury: ‘In retrospect, maybe it was silly to try and dig the whole garden in one day.’ When this pattern repeats itself a few times, we start to wonder if we shouldn’t do something to get into better physical shape. How difficult can it be, after all? Fired up with enthusiasm, we head for the gym. Often, the problem turns out to be more stubborn than we expected: ‘At first, training got me out of breath pretty quickly. That improved within a couple of weeks. But my muscles ache for ages afterwards, I tell you! The pain lasts a lot longer than I remember it used to. I need more time to recover, to get back on an even keel. Then I’m okay for a while, but my knee is still my “Achilles heel”. It’s stiff and painful, and it doesn’t get better, no matter how much I exercise.’ After 50 years of being lived in, our bodies seem to have become fragile — a persistent injury develops, and a visit to the physiotherapist is unavoidable. ‘I never had trouble with my knee before,’ we tell the therapist in consternation. Our training plan, so valiantly begun, now has to be scaled back.

Charles Darwin and Peter Medawar understood: from an evolutionary biology perspective, there is no reason at all for us to get old. The development of individuals from birth to sexual maturity is key. Humans need to reproduce and care for their children, so that they, in turn, can reach sexual maturity and produce offspring of their own. Our DNA, the blueprint for our bodies, creates an ‘eternal’ cycle. The term Darwin coined to describe the capacity for such cyclical repetition was fitness. For Darwin, this did not mean physical strength or resistance to disease; fitness is the capacity and the drive to have children — the more, the better. It is not only our physical constitution that is important in this ‘fitness programme’, but also our psychological makeup. And, of course, we put our own offspring first, and we feel a strong sense of responsibility towards them, since our children are dependent on us for a long time before they are ready to leave us and start their own families.

We learn to walk, talk, survive, and love — all biological functions, in fact — for the sake of this fitness programme. We are the product of natural selection, the mechanism behind evolution. Individual members of a species that are well adapted to the environment they live in have a greater chance of surviving and being able to care for their offspring than those that are less well adapted. Since those better-adapted individuals pass on the necessary traits to their offspring, well-adapted individuals will gradually come to predominate in the population. This is what Darwin called survival of the fittest.

In humans, this fitness programme lasts for about 50 years. The necessary information is stored in our DNA. First of all, there is the biological miracle that a defenceless little baby can develop into a unique person in the space of fifteen to twenty years. This development is rigorously programmed, and evolutionary biology helps us explain the behaviour of adolescents. Natural selection makes young adults ambitious risk-takers, thirsty for knowledge, with a craving for affection and sex. Without these characteristics there would be no fitness, and our species would soon die out.

This developmental stage is followed by adulthood. Our fitness programme makes us strong so that we can survive long enough to bring up our children. This is why vigour, decisiveness, and problem-solving abilities are also subject to natural selection. Fitness requires an optimistic outlook on life, combined with a realistic appreciation of our own abilities. In adulthood, it is also important that our bodies and minds develop in tandem with one another. Fertility, and in particular the female cycle, is complex and vulnerable; even the slightest physical or emotional stress can throw it out of kilter, with infertility as a result. Next, people have to want to have sex, otherwise no new life will be created.

And then, after a period of two generations, everything in life deteriorates. Like Buddhist monks who have spent weeks creating a mandala out of tiny grains of sand, with meticulous attention and accompanying rituals, only to brush it away in an instant with a sweep of their hand: the ceremony is over, the mandala has served its function. Many older people are able to joke about the fact that their body has started to sag, but many younger people begin to panic at the mere thought of it. Some dread the advent of their 30th birthday: ‘Will I still look good?’ Some men go grey or bald even before they reach the age of 30. Baldness is caused by a deterioration of the hair follicles. Greying is due to a similar process: the follicle is still healthy, but the melanin-producing cells deteriorate and are no longer able to create the pigment that colours our hair — just like an empty ink cartridge in a printer. Irrespective of how seriously you are personally affected by baldness before the age of 30 or grey hair before the age of 40, the evolutionary fitness programme remains unaffected. You fall in love before you’re 20, leaving ample time to have children before you reach 30. Baldness and grey hair do not appear before you have children to care for; by then, there is no longer any need for you to be attractive.

However, ageing is more than just turning bald and grey. The time it takes a person to complete a marathon gives a precise indication of the state of development or decline their body is in. Before you can complete a marathon for the first time, you need to have reached adulthood and to have run endless kilometres in training. If you then continue training, the time you need to reach the finish line will fall rapidly. The fastest finishing times are reached at about the age of 30. Your chances of becoming an Olympic champion later in life than that are negligible, no matter how hard you train. This 42-kilometre stress test is a ruthless indicator of the fact that your physical performance level is in decline — much earlier than many people expect. The fate of speed skaters and racing cyclists is no different. How many thirty-somethings do we see on the medalists’ podium? But top physical performances are not necessary in the daily life of an average adult in their thirties, consisting of caring for home and family. If you perform physically at an average level, it will be twenty more years before a day’s digging in the garden leaves you unable to get out of bed the next morning.

In old age, running speed is a good gauge of the amount of permanent damage that has accumulated in our body, and of the remaining functions it possesses. Some older people stay nimble far into old age. On average, such people live longer than their stiffer, less agile peers who have more difficulty moving. Of all the measures available to doctors to help them assess how frail and how likely to die their patients are, running speed appears to be one of the best. It indicates how well not only the muscles and joints are functioning, but also the nerves, heart, and lungs. Having reached old age without loss of mobility is a sign that the ageing process has not yet seriously affected the body.

The development and ageing of our brains follows the same pattern as the rest of our body. For most of us, it is not easy to accept that our body’s functions will decline, but we find it especially disturbing when our brains begin to let us down early in life. It is common knowledge that no mum or dad, grandma, or grandad stands a chance of winning in a game of Pelmanism against their children or grandchildren, even when sheer frustration after a few lost rounds prompts them to try their hardest to win. As their tension level rises, their performance just keeps getting worse.

Children’s ability to recognise visual images, to associate them with a particular time and place, and to store that information in their memory and to recall it on demand is truly phenomenal. Early in life, the ability to recognise your father and mother instantaneously, at any time, from among thousands of grown-ups, is vital — natural selection has provided our children with this remarkable skill. As we get older and more independent, we quickly become less skilled at this trick — but, still, anyone can continue to enjoy a game of Pelmanism right up to their 100th birthday and beyond. On average, enough brain function remains as residual capacity to give someone a fair game.

Maths professors are usually appointed around the age of 30. Einstein produced his most important work before the age of 40. Apparently, this is when human beings reach the summit of their theoretical and algebraic abilities. This is early, but it is significantly later than puberty, the onset of adulthood, from an evolutionary point of view. Behavioural imprinting, spatial awareness, memory, and reproductive ability are at an optimum when we are young; but, despite the deterioration of these individual cognitive abilities, humans become better at solving complex problems as adults. The effective sum of these individual functions increases because they are increasingly attuned to one another. This is also true of difficult emotional and social problems, which require empathy and managerial skills to solve, and those competencies usually come with practice. That is why the environment in which we grow up is so important. It is principally a biological fact that you can become a father or mother at the age of 20, or that you can be appointed to a maths professorship at 30, but it is experience and culture that turn you into an effective manager, a grande dame, or a wise man. This is why we do not begin to mature until our forties, and that is when we face the greatest challenges in our personal and professional lives.

RITES OF PASSAGE

For as long as humans have existed, we have marked important milestones in our lives — birth, coming of age, marriage, death — with rituals. These rituals help individuals and society as a whole to move on from an old role and assume a new one. Baptism, confirmation, our first day at school, college hazing, or initiation ceremonies are all examples of rituals used in Western society to mark times of transition. The French anthropologist Arnold van Gennep (1873–1957) called these rituals rites de passage. He saw these ‘rites of passage’ as part of the process of socialisation — the adjustment individuals make to the society they live in.

From the sixteenth century, a popular motif in engravings was the ‘Steps of Life’, or the ‘Ages of Man’, where the stages of a man’s life were represented on a rising and descending staircase, charting the chronological ascent from birth to a climax at the prime of life, and then descent towards eventual death. Most engravings show the trajectory of life from age 0 to age 100, with each step on the stairs representing ten years. It starts with a baby, full of future promise, on the left, and it ends with a hunched old man on the right, a shadow of his former, vital self. Youth and old age are shown as two extremes, on the lowest steps of the staircase, as if to say that the beginning and the end of life are fixed. Depicted right in the middle, on the top step, is a man aged 50, in all his midlife splendour. But this is also where engravings differ greatly: some of these men in their prime are represented as honoured military heroes, others as successful merchants, and yet others as aristocratic noblemen. Finally, the foreground nearly always shows a depiction of the Last Judgement. The concept of the course of human life was unquestioningly bound up with prevailing Christian morality. That was undoubtedly part of the reason why prints of ‘The Ages of Man’ adorned the walls of so many European parlours right up until the early twentieth century.

While the majority of these engravings showed a man in his prime at the top of the staircase, some showed the ‘Ages of Woman’ instead. The women depicted in this way are shown reaching the top step at the age of 30! Are we then to assume that the ageing process sets in earlier for women? There is no biological reason to believe so. In fact, the opposite is the case. On average, women live longer than men, under almost all circumstances. In short, the early decline of women as shown in these engravings is primarily a reflection of their social status. These prints are a blunt reminder of how people used to think about the social progression of men and women through their lives. Worse still, some post-menopausal women were thought to possess supernatural powers. They could ‘make the grass wither and the fruit shrivel on the tree’. This did not, of course, apply to high-born women.

The rites of passage depicted in the ‘Ages of Man’ show how closely age, health, social status, and environment are bound up together. It is for this reason that it is important to differentiate between the various manifestations of age and ageing: our chronological age, our biological age, and our social age. The relations between these types of age depend greatly on the time we live in. To some extent, age and environment are inextricably linked, but more often, this relationship is the result of the choices we make, both consciously and unconsciously.

Chronological age is the most direct manifestation of ageing — indicated by the celebration of our birthday each year. Sometimes they are special birthdays, marking particular milestones in life. This is what is called our social age. For example, we attain the status of legal majority on our 18th birthday, along with the right to vote and to marry without our parents’ consent. It is simply a societal choice to designate 18 as the age of majority; not all that long ago it was still 21. At the other end of the spectrum of life, 65 is the age in many countries at which employees can legally be dismissed without further reason. This right of employers came into fashion in the late-nineteenth century, after the German chancellor Otto von Bismarck’s grand gesture of paying out pensions to the very few civil servants who made it to 65 and beyond. For many, both employers and employees, this cemented 65 as the normal age at which to leave the world of work behind and to start enjoying retirement. But there are great differences between countries. The French reach retirement age at 60. In China, it is 55 for men, and 50 for female workers.

It is understandable that a society needs to have clearly defined life stages in order to function, but those definitions are based on the assumption that the quality of our bodies and minds is fixed in relation to our chronological age. A human being’s sequential development is fixed and unchangeable. Babies learn to walk before they learn to talk. But the speed at which they develop can differ enormously from child to child. Exceptions notwithstanding, the human body is ready for sex and reproduction by the age of 18, but the developmental level of many people’s minds by that age is far from adult. The biological development of the brain is still ongoing, and will not even begin to reach completion until we turn 30. For many, the rights and obligations of legal majority come far too soon, but for others they are attained much too late. And there is even greater variation between people when we look at the deterioration of their physical and mental state — that is, the ageing process — in later life. Some people look 80 when they are only 50; they are well past their prime. But the opposite can also be true — people in their eighties who look middle aged. This variability in physical and mental qualities is what we call our biological age, and deterioration in biological age is the second manifestation of ageing. It is not logical to send someone into retirement at a predetermined chronological age — at least, that is, if the age of retirement is to be based on medical and/or biological grounds. For some, retirement comes (much) too early; for others, much too late.

The rhythm of life — the sequence of development and ageing — does not vary between different mammal species, but the pace at which everything happens certainly does. In general, there is a relation between the speed at which a body develops and the rate at which it ages. In rodents, for example, everything happens quickly. Mice reach sexual maturity in six weeks, and rarely live longer than two years. But for other animals — humans and elephants, for example — all this takes much longer. The latter can also live to great old age; pregnancy is longer in elephants than humans, and elephant calves take a long time to develop and reach adulthood. The time required to develop by most small mammals, such as cats and dogs, is somewhere between that of mice and elephants.

Even within individual species there is a link between developmental speed and ageing. Experiments on laboratory animals have shown that rapid growth, or catch-up growth after a period of food scarcity, is associated with accelerated ageing. Studies have also been carried out to investigate whether there is a link in humans between the onset age of puberty and/or the menopause, and the development of disease in old age. These studies revealed a positive correlation between a late onset of puberty, body height, and bone strength. The conclusion is that a lengthy period of development gives a better result, biologically speaking. However, the other side of the coin is that tall people have an increased risk of developing cancer. The prevailing interpretation is that excessive growth can have negative consequences.

Unlike chronological age, which is immutable, there appears to be a great deal of possible variation in the biological development of individuals of one species, and this is what biologists call ‘plasticity’. A dog is a dog and a human is a human, but each individual can have a very different life story. Nematodes — also called roundworms — can undergo a temporary metamorphosis in reaction to harsh conditions. This is the worms’ so-called ‘dauer’ stage (from the German word for ‘endurance’) in which they enter a kind of stasis, do not reproduce, and are able to resist adverse external influences. Nematodes can survive long periods under unfavourable conditions in this way. When conditions improve, the worms simply resume their normal lives and begin reproducing again. Scientists are keen to discover the principle that underlies this dauer stage — not only because it is enigmatic in itself, but also because it could potentially be hugely important in human medicine. Nematodes, with their ability to enter a dauer stage, have a lifecycle characterised by a long, disease-free existence, seemingly without having to pay a biological price for this.

Not every species is endowed with the ability to change its lifecycle so deeply and yet so flexibly, depending on the surrounding conditions, by simply ‘taking a break’. Human beings’ talent for this is small. Bears that hibernate have slightly more talent, but the greatest talent in this area must be that of the abovementioned nematode worms. ‘Plasticity’ is seemingly written into their genetic code, and for some species it is a necessary feature to protect them from extinction.

The historical period we live in has a great influence on the way ageing manifests itself. A comparison of the present with a century ago shows that the course of our lives is closely dependent on our environment. Whereas life expectancy stood at about 40 years just a few generations ago, it has now more or less doubled. And we are now staying healthy for much longer. While people in a traditional setting were fully prepared for life by their eighteenth birthday, those reaching adulthood now are expected to have many more mental and emotional skills than their predecessors, but they still have a lot to learn beyond the age of 18. And, if anything, those expectations seem to be increasing rather than decreasing.

In the modern world, we must continue to develop and adapt throughout our lives. Social and technological developments happen so quickly that acquired knowledge and skills are soon outdated, and people are soon no longer adequately equipped to function in society. This may be why men today reach the apex of their career well before they turn 50. Conversely, women are no longer sidelined from society at the age of 30. It is difficult to discern any patterns in all these changes. Each era, each society, has its own opportunities, moral code, and customs. But, of course, we cannot completely detach all the social expectations we place on ourselves or each other from our biological age, the moment we reach adulthood, and the time we become sick and dependent on others.

The good news is that the modern age offers us more possibilities than ever before. Inspired by the Paris student revolts of 1968, activist groups sprang up all over the world, which aimed to break away once and for all from traditional male and female life trajectories as depicted in those ‘Ages of Man’ prints. They wanted to untie the knots connecting chronological, biological, and social age, as they felt they had become obsolete. Major advances in medicine and technology added momentum to the developments taking place in society. Sex and reproduction, which until then had been directly linked to chronological and biological age, now became a matter of choice. The contraceptive pill gave both women and men the power to choose whether and when sex should lead to reproduction. With this, the concept of social age also began to run adrift. Marriage was no longer the rite of passage into parenthood. The responsibility of having children could be postponed at will, or entered into outside of wedlock. Here, too, advances in medicine, and the loosening of social constraints mutually reinforced each other. In vitro fertilisation allowed otherwise infertile couples to have children with the aid of a donor. It now also became possible for women to have children at an age that was previously impossible. In short, the desire for a new, more self-determined, and individual life trajectory has become reality because issues of fertility, ageing, and chronological age have been, in part at least, disconnected from each other.

Adapting to the environment — socialisation, as Arnold van Gennep called it — is essential for survival and reproduction to create the next generation. Natural selection plays a crucial part in this. The plasticity of the nematode worm, with its ability to change form and to switch off the ageing process in doing so, is not something we human beings share. The rhythm of human lives is largely fixed. But we are increasingly able to influence biological processes that used to be thought of as immutable. It is fascinating that we have been able to break down the rigid relation between chronological age and biological age in the past 50 years because it suits us better socially.