Life Time: Your Body Clock and Its Essential Roles in Good Health and Sleep

Forty years ago, as an undergraduate studying zoology at the University of Bristol, I knew I wanted to be a scientist, but I had little real idea of what that meant or involved. The ‘body clock’ was just a fuzzy concept in my young, unfocused free-wheeling brain. However, during the final year of my undergraduate degree, I was a volunteer helper at an international meeting on biological rhythms. The job was not demanding, and I swanned about listening to the lectures and met the then leaders of the field. With the confidence – perhaps arrogance – of youth, I assumed that these scientific titans would want to speak to me just as much as I wanted to speak to them. Most were incredibly generous with their time, although I did learn not to approach one very senior professor over breakfast (it’s amazing how much meaning can be conveyed in a stony silence and a fixed stare at a greasy sausage …). It was a formative experience at many levels, and I soaked up the science like a sponge. Without my knowing it, this symposium defined my life-long interests and sparked an ambition to join this extraordinary group of international academics who were working on the fast-emerging science of biological time. My career as a scientist, from my undergraduate days to my current position as Professor of Circadian Neuroscience and Director of the Sir Jules Thorn Sleep and Circadian Neuroscience Institute at Oxford has allowed me to gain insights from, and occasionally share new knowledge with, colleagues from all over the globe. In a sense, this book represents the distillate of what I have learnt in studying the nature of biological time over the course of four decades. My hope is that I can convey to you some of the excitement, wonder and undiluted pleasure I have experienced over the years.

In the past few decades, there has been an explosion of thrilling new discoveries in and around the science of the body clock and the 24-hour biological cycles that dominate our lives. The most obvious of these cycles is the daily pattern of sleep and wake. Surprisingly, most books discuss the body clock and sleep separately. However, new research tells us that such a disconnected approach tells only part of the story. You cannot properly understand sleep without understanding the body clock, and sleep in turn regulates the clock. In the pages that follow, the body clock and sleep will be considered together as two intimately linked and intertwined areas of biology that define and dominate our health. In so many cases, your ability to succeed or fail, from driving home safely after work or dieting to achieve weight loss, will depend upon whether you are working with or against these 24-hour cycles. So much has happened in this area of science and medicine that it is often difficult to disentangle fact from fiction. In terms of health, sensible advice is frequently transformed into strident orders that resemble the commands shouted by a Regimental Sergeant Major on the parade ground: you ‘must’ get eight hours of sleep; you ‘must’ continue to share a bed with a partner who snores; you ‘must not’ use a light-emitting eReader (LE-eBook) before bed. So rather than being recognized as a loyal friend, biological rhythms and sleep are frequently portrayed as the enemy that needs to be wrestled, subdued and defeated. Instead, we need to understand and embrace these rhythms.

In this book, I have attempted to unpack the science of body clocks and sleep, making some of the amazing and exciting discoveries accessible, and hopefully in a format that is fun and easy to read. I have been able to draw from my own personal experiences over the past forty years as a scientist in this field, and have benefited immensely from discussions with friends and colleagues, who have contributed directly to our current understanding of biological time. I provide the evidence behind our current knowledge of the science, and how this evidence can be used by each of us to make more informed decisions about improving our lives. From getting better sleep, to organizing our daily activities and even why we may benefit from taking medications or being vaccinated at a particular time of day. The information in this book will also give you a greater understanding of the behaviour of others, including why teenagers and the elderly might struggle to get restorative sleep, why your mood and decision-making skills may change from morning to afternoon, and why the risk of divorce is higher in those doing night shift work. I have emphasized throughout this book that we are all very different, and that while it is possible to make generalizations, taking an ‘average value’ can be misleading. Although the average length of the menstrual cycle in women is 28 days, only 15 per cent of women actually have a 28-day cycle. Your body clock and sleep biology can be likened to your shoe size: one size does not fit all, and making us all wear the same shoe size would be not only foolish but potentially harmful. The failure to recognize this variation is why some general advice in the media can be either overly simplistic or deeply unhelpful.

Sleep and daily rhythms emerge from our genetics, physiology, behaviour and the environment, and like most of our behaviours they are not fixed. These rhythms are modified by our actions, how we interact with the environment, and how we progress from birth to old age. From infancy to advanced adulthood, our body clock and sleep patterns change profoundly, but these age-related changes are not necessarily bad. We should stop worrying about our sleep and accept that ‘different’ is not necessarily worse. Some of the advice we are given can be just wrong, emerging from the murky world of ‘received wisdom’. Such ‘wisdom’ can be ancient and extend back to the beginnings of recorded history. However, as we shall see in the following chapters, the repetition of an idea does not necessarily guarantee legitimacy. For example, flipping babies helps sort out their sleep. According to this old tale, flipping the baby forward, head over heels, will reset the child’s internal clock so that it will sleep at night and be awake during the day. There is absolutely no evidence for this. Indeed, as a tale it may well have its origins in parental desperation. Chronic sleep deprivation, not least in parents, can badly affect judgement and our ability to act rationally! Another often-repeated myth is that the pineal gland hormone melatonin is a ‘sleep hormone’. It is not, and in the following chapters I shall explain why.

My message throughout this book is that all of us, as individuals and as members of society, should make some effort to understand and act upon the new scientific knowledge of biological time. But why bother? For me, it makes sense in a complex and demanding world to achieve the best physical and mental health we can. Such knowledge will help us deal with the many and varied insults that life flings at us. However, there is more. If you want to embrace life, be creative, make sensible decisions, enjoy the company of others, and view the world and all that it has to offer with a positive outlook, then embracing biological time will help you do this. Why not make the most of the time we have, and maybe even extend that time?

The Tick-Tock of the Biological Clock

The entrenched arrogance which goes with being human means that most of us assume that we are above the grubby world of biology, and that we can do what we want, at whatever time we choose. This assumption underpins the modern 24/7 society, and an economy that is dependent upon night shift workers to stock our supermarkets, clean our offices, run our global financial services, protect us from crime, repair our rail and road infrastructure, and, of course, care for the sick and injured when they are most vulnerable. All of this happens while most of us sleep, or at least try to sleep. Although night shift work is the most obvious disruptor of our body clock and sleep, many of us experience shortened sleep as we try to squeeze more and more work and leisure activities into a daily schedule that is already over-packed and bursting at the seams. So we push these ‘additional’ activities into the night. Our full-scale occupation of the night has been possible because of the widespread commercialization of electric light across the world since the 1950s. This extraordinary and wonderful resource has also allowed us to declare war upon the night, and, without really appreciating what we have done, we have thrown away an essential part of our biology.

We are, of course, not able to do what we want at whatever time we choose. Our biology is governed by a 24-hour biological clock that advises us when it is the best time to sleep, eat, think, and undertake a myriad of other essential tasks. This daily internal adjustment allows us to function optimally in a dynamic world, ‘fine-tuning’ our biology to the profound demands imposed by the day/night cycle generated by the 24-hour rotation of the Earth upon its axis. For our bodies to function properly we need the correct materials in the right place, in the right amount, at the right time of day. Thousands of genes must be switched on and off in a specific order. Proteins, enzymes, fats, carbohydrates, hormones and other compounds have to be absorbed, broken down, metabolized and produced at a precise time for growth, reproduction, metabolism, movement, memory formation, defence and tissue repair. All this requires a biology and behaviour that are prepared and ready at the right time of day. Without this precise regulation by an internal clock, our entire biology would be in chaos.

For a relatively new branch of biology, and an emerging branch of medicine, the science of body clocks has its roots much earlier than might be expected, going back to the late 1720s and the study of a plant with the Latin name of Mimosa pudica – meaning ‘shy, bashful or shrinking’ – also called the ‘sensitive plant’. This member of the pea family, familiar to many gardeners, has delicate leaves which fold inward and droop when touched or shaken, and then reopen a few minutes later. In addition to responding to touch, the leaves fold up at night and open during the day. Jean-Jacques d’Ortous de Mairan, a French scientist, studied these plants.

De Mairan’s seminal observation, for our story, was that Mimosa leaves continue to show this rhythmic folding and unfolding leaf movement for several days in complete darkness. He was amazed; it was clearly not the change in light and dark that was driving this cycle, so what could it be – could it be temperature? Daily changes in temperature were investigated in 1759 by another French scientist, Henri-Louis Duhamel du Monceau, who took Mimosa plants into a salt mine, where there were conditions of constant temperature and darkness, and found the rhythms continued. More than 100 years after this, in 1832, a Swiss scientist, Alphonse de Candolle, studied Mimosa plants under constant conditions and showed that these drifting or ‘freerunning’ rhythms in leaf opening and closing were not exactly 24 hours but around 22–23 hours.

Over the next 150 years, daily rhythms that continued under constant conditions with a rhythm close to, but not exactly, 24 hours were observed in many plants and animals. Such rhythms were later called circadian rhythms (circa means ‘about’, and dia ‘a day’). However, it was fairly late in the game that circadian rhythms were studied in humans. Hints that they exist in us came from observations in the late 1930s by Nathaniel Kleitman. From 4 June to 6 July 1938, Kleitman and his student Bruce Richardson remained deep in Mammoth Cave, Kentucky. There was no natural light and the temperature was a constant and cool 12.2°C. Light was provided by lanterns, so conditions were not completely constant. And they had to share the cave with a large population of curious rats and cockroaches. To stop them crawling into their bedding, the four legs of their bunkbed were placed into large tins containing disinfectant. They recorded sleep and wake times and measured their daily rhythm of body temperature. These observations showed that they continued to show roughly 24-hour cycles in body temperature and sleep/wake timing.

The true significance of these findings was not realized until the 1960s. One of the pioneers in the field, Jürgen Aschoff had an underground ‘bunker’ built in Andechs, a town in Bavaria with a Benedictine monastery that has brewed beer since 1455. University undergraduates, when not in the bierkeller, were housed underground in the bunker under constant dim light, and isolated from any external environmental time cues, but they did have access to a bedside lamp. So, again, they were not really under constant lighting conditions. Student sleep/wake cycles, body temperature, urine production and other ‘outputs’ were measured over many days and were shown to have a rhythmic daily pattern of about 24 hours under these semi-constant conditions. From such experiments, the human body clock was estimated to run at around 25 hours. More recent studies from Charles Czeisler’s group at Harvard University suggest the average human clock ticks with a rhythm closer to 24 hours and 11 minutes. This difference in period was always a point of friction between Aschoff and the Harvard team. And the consensus today is that the difference was caused by the use of bedside lamps in the bunker experiments. Aschoff was a remarkable man and I learnt much from him – both scientifically and socially. About twenty-five years ago at a summer school party in Bavaria I opened a bottle of wine. Several minutes later there was a roar from Aschoff: ‘Who has left the cork on the corkscrew?’ I admitted that it was me and he said for all to hear: ‘You never leave the cork on a corkscrew, it is the height of bad manners.’ I have never done it since.

By the 1960s, circadian rhythms, which persist (freerun) under constant conditions and have a period close to but not exactly 24 hours, had been identified in many different plants and animals, including us. And everyone (well, nearly everyone) accepted that these rhythms were generated biologically – they were ‘endogenous’. As in all branches of science, unless you live under a dictatorship, there is never complete agreement about anything. But dissent is good because it makes scientists refine their experiments to build an even stronger ‘evidence base’ for the hypothesis being tested. The most prominent dissenter was Professor Frank Brown at Northwestern University in Chicago. He believed that biological rhythms were driven by some natural geophysical cycle such as electromagnetism, cosmic radiation or some other, as yet unknown, force. Brown’s central, and not unreasonable, argument was that no biological mechanism could be independent of temperature. When you increase temperature, biological reactions speed up, while cooling slows them down. But for a clock to keep time accurately it has to always run at the same speed. More observations were needed, and studies in plants and ‘coldblooded’ insects showed that biological clocks would indeed keep good time – despite huge changes in environmental temperature. Brown was wrong, but his challenge led to experiments which showed conclusively that biological clocks were indeed ‘temperature compensated’. Endogenous 24-hour biological clocks had to exist!

An internal clock allows you to not only know the time, but also to predict time, or at least predict regular events within the environment. As I mentioned, our bodies need the correct materials in the right place, in the right amount, at the right time of day, and a clock can anticipate these different needs. By anticipating the approaching day our bodies are prepared in advance so that the ‘new’ environment can be exploited immediately. Blood pressure and metabolic rate, along with many biological processes, rise before the new dawn. If we merely responded to the light of dawn to switch us from sleep into activity, then valuable time would be wasted getting our energy usage, senses, immune system, muscles and nervous system tuned up for action. It takes several hours to switch from sleep to activity, and a poorly adapted biology would be a major disadvantage in the battle for survival.

Two of the three essential features for an internal circadian clock have been touched upon so far – the ability to keep ticking with a period of about 24 hours under constant conditions, and to maintain a near 24-hour period even when environmental temperatures vary dramatically, showing temperature compensation. The third feature is called ‘entrainment’; this capability is incredibly important and will be discussed in detail in chapter 3. I am, perhaps, a little biased about the importance of entrainment because this is what I have worked on for most of my career. As mentioned, circadian clocks do not run at exactly 24 hours, but tick a little faster or a little slower. In this way, circadian rhythms resemble an old mechanical grandfather clock which needs a slight daily adjustment to make sure the clock is set to the ‘real’ astronomical day. Without this daily resetting, the clock will soon drift and be out of alignment (freerun) with the environmental day/night cycle. A biological clock is of no use unless it is set to local time. For most plants and animals, including us, the most important ‘entrainment’ signal that aligns the internal day to the external world is light, especially the changes in light around sunrise and sunset. In us, and other mammals, the eye detects dawn and dusk to entrain our circadian rhythms, and eye loss prevents this resetting. People who have lost their eyes as a result of genetic disease or in combat, or because of a tragic accident, drift through time, experiencing periods when they get up and go to bed for a few days at the correct time, before they drift off again and want to sleep, eat and be active at the wrong time of day. A body clock with a period of 24 hours 15 minutes would take around 96 days to travel from 12 noon back around to 12 noon again, getting later by 15 minutes each day. Blind individuals experience something similar to constant jet lag. They become ‘time blind’, a state that I will discuss in detail in later chapters.

The Big Sleep

Although the sleep/wake cycle is the most obvious of our 24-hour rhythms, hardly anybody talked about sleep at the meetings I attended in the early days. Sleep seemed to me, and to so many others at the time, too murky and nebulous a subject to get clear answers about. Sleep was also associated with abstract philosophical notions such as the ‘mind’, ‘consciousness’ and ‘dreams’. It was too impenetrable for most of us. This notable lack of interest in sleep by most circadian researchers, including myself back then, reflected the divergent origins of the fields of circadian and sleep research. The science of circadian rhythms was established by biologists working on every sort of plant and animal. By contrast, sleep research has its origins in medicine and recordings of the electrical activity from the human brain – ‘brainwaves’. Sleep was, and still is, studied intensively using electroencephalography (EEG), and interests were focused on how the EEG changed during different stages of sleep and disease. Based upon the size and speed of brainwave activity recorded from the brain by EEG, as well as eye movements and muscle activity, sleep is defined as either rapid eye movement (REM) sleep, or one of three stages of non-rapid eye movement (NREM) sleep. When we are awake our EEG shows small and rapid oscillations in our brain’s electrical activity, but as we descend into NREM sleep these oscillations become larger and slower until we reach our deepest sleep, often called slow-wave sleep (SWS). From this state of deep sleep, the EEG transitions into faster and smaller oscillations once again and we enter REM sleep, which has been called ‘paradoxical sleep’ because it resembles the EEG seen during wake. During REM sleep we also experience paralysis from the neck down, while our eyes move rapidly under our eyelids from side to side – hence the name. This NREM/REM cycle occurs every 70–90 minutes, and across a night of sleep we experience four or five NREM/REM cycles, waking naturally from REM sleep. Around 15 years after the experiment in Mammoth Cave, Nathaniel Kleitman and another student, Eugene Aserinsky, discovered and named REM sleep in 1953 and linked REM to the time when we experience our most vivid and complex dreams. If you have a dog, you may have noticed that while asleep the dog may whimper or growl and make running movements as if chasing a rabbit. Such behaviours have led some to suggest that dogs, and indeed many mammals, also experience dreams during REM sleep. If you don’t have a dog, you can always watch your sleeping partner in REM. It’s fascinating, but a bit disconcerting for them if they wake and become conscious of your scrutiny!

It is only in the past 20 years, and most notably during the last 10, that circadian and sleep researchers have begun to talk to each other seriously and attend the same meetings. Indeed, meetings nowadays are designed to attract both groups of scientists, and today I consider myself to be both a circadian and a sleep researcher. So what got me into sleep? In my case there was a clear and defining moment, arising from a short discussion that irritated me intensely. In my former job, I spent quite a bit of time in the same building with neurologists and psychiatrists, and back in 2001 I bumped into a psychiatrist in one of the unreliable lifts at Charing Cross Hospital in west London. ‘You work on sleep, don’t you,’ he said to me. ‘No,’ I replied politely, ‘I study circadian rhythms.’ He continued, oblivious of this subtlety, and said, ‘My patients with schizophrenia have terrible sleep, and in my view that’s because they don’t have a job – so they go to bed late and get up late, which means they miss my clinic, are socially isolated and so can’t make friends.’ This ‘unemployment’ explanation made no real sense to me, so I teamed up with another psychiatrist to study patterns of sleep in a group of 20 individuals with a diagnosis of schizophrenia. We compared sleep in this group to unemployed individuals of the same age. The results left me gobsmacked. Sleep/wake patterns in people with schizophrenia were not just bad, they were smashed, and utterly different from the unemployed individuals, who showed similar sleep patterns to employed individuals.

Individuals with schizophrenia also had very little or no SWS and abnormal REM sleep. I wanted to know why sleep had fallen apart in these individuals, and this provided the starting point to study sleep in mental illness, and then later in other health conditions. Interestingly, many of my circadian colleagues, for a whole variety of different reasons, have also ‘moved into sleep’ in the past decade. Perhaps age has given us wisdom, or maybe courage? Even more importantly, a new generation of neuroscientists armed with multiple and powerful techniques to examine the brain have chosen to study sleep, and are now delivering amazing new information.

Although a host of fundamental questions remain, sleep today is no longer regarded as the ‘black box’ that it was when I started research. Remarkable new work has greatly improved our fundamental understanding of how sleep is generated within the brain, and how sleep is regulated by our environment. We also now appreciate that during sleep we establish most of our memories, solve problems and process our emotions; we remove dangerous toxins that build up during activity; we rebuild metabolic pathways and re-equilibrate energy reserves. And if we fail to get sufficient sleep, brain function, emotions and physical health all fall apart rapidly. For example, abnormal sleep makes us more vulnerable to heart disease, Type 2 diabetes, infections and even cancer. In short, our sleep defines our ability to function while we are awake, and lack of sleep and the circadian disruption of sleep impact enormously on our overall wellbeing and health. While the evidence demonstrating the importance of sleep is clear, this massive chunk of our biology, around 36 per cent of our life, is still not fully appreciated by many sectors of society. In five years of training, most medical students will have only one or two lectures on the topic, and the information covered is usually about EEG activity during sleep, rather than the new science of circadian rhythms and sleep that I will discuss in this book. In the public domain there remains a lot of sloppy thinking about sleep. Employers assume that their night shift workers will adapt to the demands of working at night. This assumption is wrong, and as a result employees can become dangerously ill, overweight and mentally impaired, and are at a higher risk of divorce and road accidents. As our society becomes increasingly 24/7, and as we squeeze more and more into an overcrowded day, our sleep has become the hapless victim.

What I Hope to Achieve

My central aim is to empower you, the reader, by providing concrete information and guidance, based upon the latest science. You will be able to use the information in the following chapters to get a better understanding of what makes your body clock ‘tick’ and, critically, use this knowledge to develop an optimal personal routine that works for you, irrespective of age or circumstances. I want to cut through some of the myths, and maybe burst a few bubbles, including the view that teenagers are lazy and that the business executive who gets up at 4 a.m. and starts work is a role model. As you will see, this book encompasses a huge span of human biology and will hopefully stimulate you to dig deeper into many of the topics covered.

Each chapter will consider a central topic, define the science of that topic, and then address issues that impact upon our health and wellbeing. Some of the science can get a bit complex, but it is fundamental for gaining an understanding of our biology and health. The book is also structured so that you can jump back easily to earlier chapters and re-check information for a reminder. Finally, each chapter will finish with a short ‘Questions and Answers’ section designed to answer some questions that people frequently put to me and my colleagues. This Q&A section will also provide additional and sometimes oblique information. I stress that it is not my intention to provide medical advice; you should always seek this from your medical practitioner. But I will try to explain how some of your actions may be important in achieving optimal health and avoiding potential harm. Such actions include: why to eat at a particular time, when to exercise or when to take different medications, and why you should not drive in the early hours of the morning. This will not be ‘finger wagging’. The aim is to provide you with the most up-to-date information that you can either adopt or ignore, but with a clear understanding of the consequences of your actions.

You will also find an Appendix I which provides some guidance on how you may want to develop your own sleep diary to monitor your sleep/wake patterns. Appendix I also includes a questionnaire which will allow you to estimate your ‘chronotype’, and whether you are a ‘morning’, ‘neutral’ or ‘evening’ person. Appendix II provides a brief outline of the immune system, digging a bit deeper into the complexity of this important part of our biology, which is covered in chapter 11. And in terms of detail, this book has been fully referenced, and I have been guided by one of my scientific heroes, Thomas Henry Huxley, who said: ‘If a little knowledge is dangerous, where is the man who has so much as to be out of danger?’ To help you build upon the ‘little knowledge’ in this book, I have cited the relevant scientific papers that have informed the discussion. Many of these scientific publications are, or will be soon, available online as a result of ‘Open Access’, whereby published research can be accessed free of cost. Indeed, most scientific papers are freely accessible from scientific journal websites 12 months after publication.

My hope is that you enjoy this book and become inspired by the emerging science of biological rhythms, and, importantly, that you will want to apply this science to your own health, happiness and wellbeing. I also hope that, after a suitable period of reflection, you will agree with me that by embracing this knowledge you will be more creative, make better decisions, gain more from the company of others, and view the world and all that it has to offer with a greater sense of curiosity and wonder.

Oxford, January 2022