Healthy Ageing

Chapter 1

Healthy Ageing

Application of the Pub Test

The purpose of this book is to summarize the latest scientific findings on healthy ageing in a readable form that is understandable to the general public. Many publications on healthy ageing are too simplistic, non-scientific (therefore not subject to critical analysis), highly biased and largely motivated by commercial interests. Others are written in technical language, such as in academic books and in peer-reviewed scientific journals, that are not easily comprehended by the general public.

Simple explanations and points of view are actually good if based on a non-biased assessment of data. Data by itself may be non-biased: it is the human interpretation of the data that is frequently biased. Unfortunately, much of the available information on health and ageing is highly biased and often confusing, in many cases deliberately so as in food labelling.

The information provided in this book is based on prime quality publications in high-impact peer-reviewed scientific journals. In these publications there is a considerable amount of technical language, vast amounts of data and with that comes lots of statistical analyses. The fact that much data crunching is required for the statistical analysis immediately alerts one to the observation that perhaps data on health and ageing is not that clear-cut. On the other hand, one can equally argue that application of precise statistical analysis to the data is a good thing and suggests a rigorous assessment of the scientific data.

The Reader is encouraged to consult any publications cited in this book which are of personal interest. Many scientific publications are freely available to the general public. For example, try searching PubMedCentral which is an archive of scientific journal articles (www.ncbi.nim.nih.gov/pmc/articles) and lets you know if free access or download is available; other publications may require a fee (expensive) for a single item while others may be available through a higher education facility.

In any case, the Abstract or Summary of many scientific publications is generally freely available. Although scientific publications are written for a specialized audience, you are encouraged to read the Abstract/Summary of articles of interest to you, and the Introduction and Conclusion are generally also worthy of a read although these can be quite daunting for readers with non-scientific backgrounds. The most difficult and technically challenging sections are the Methods, the Results and, of course, the inevitable statistics.

Here, I express my bias with respect to statistics in that I do not get very excited if a researcher concludes that their data demonstrates ‘a statistically significant 10% decrease in mortality’ as a result of, say, a certain diet or lifestyle. In my opinion, a 10% decrease or increase is within experimental error, especially when one is considering health and ageing in humans given the fact that every human is unique with respect to genetics, diet and lifestyle. The 10% figure should be used as a guide as to the trend towards a decrease or increase in mortality or health benefit. Moreover, statistical corrections for confounders affecting health and ageing such as smoking, education, exercise, alcohol, occupation, weight and marital status are so highly personal that statistical corrections for these confounders may not be, well, statistically meaningful. Statistically significant does not automatically translate to ‘clinically significant’ when it comes to health and ageing. Nevertheless, for a balanced view, many of the publications on health and ageing do apply a statistical correction for some of these confounders.

One definition of a statistician is a person who has their feet in a bucket of ice-water and their head in an oven but claims on average that everything is fine.

One has to be aware that a study published in a peer-reviewed scientific journal, that is an article that has been appropriately refereed by acknowledged experts in the field, signifies that the research is of a certain standard but may be subject to modification should further research provide contradictory or supportive data. This is the nature of scientific research.

The world is rapidly changing. By that we mean not only the environment (e.g. think climate change) but also in the very short term the ageing human population. In many nations the ageing population is currently, and most certainly will be, in the next ten to twenty years, providing real challenges. The data are impressive. For example, in Western European nations, 15% to 20% of the population are over 65 and in Japan it is already 27% (World Bank, type ‘population over 65’). Thus, it is not surprising that there is widespread interest in the demographics of ageing by governments, businesses and individuals given the social and financial impacts on society.

There is a paradox, at least in developed nations. Health care consumes a very high proportion of private and public funds and is very much focused on treatment (e.g. general practitioners, hospitals) as opposed to prevention. The latter is surely the preferred option as prevention is better than cure (certainly much cheaper). Not smoking is the classic example. In relation to healthy ageing, there is no doubt prevention or at least slowing down the ageing process is the way to go. Once you have aged, there is simply no cure; it’s much better to age well and healthily.

What Do We Mean by Healthy Ageing?

In 2015, the Gerontological Society of America solicited articles specifically focused on the concept of successful ageing. In the Editorial of the special issue of the journal of the Gerontology Society (Pruchno, Editorial, 2015) it was quoted that in an article by Depp and Jete (2006), a review of twenty-eight published studies on successful ageing, resulted in twenty-nine definitions of successful ageing. It is most unlikely that any definition of successful ageing will be universally acceptable, at least in the academic arena. There are simply too many egos at stake.

To some extent, individuals who have reached their one hundredth birthday, the centenarians, may be deemed to have aged successfully. Individuals in good health and relatively free of chronic disease who are in their eighties and nineties, the octogenarians and nonagenarians respectively, may also be regarded as having aged successfully.

In much the same way as people judge other people on first observation as, say, charismatic, attractive, unattractive, trustworthy etc, a successfully aged individual may be judged by body language as in e.g. how they talk and walk. The latter, as in walking gait and speed, is actually a reasonable assessment about the physical condition of an elderly individual and their progress towards health ageing (Studenski et al., 2011; Boulifard et al., 2019; Rasmussen et al., 2019). Of course, one is very well aware that judging a person by appearance is deceptive, as in judging a book by the outside cover; the inside or contents of the book is what really matters.

Facial recognition software is increasingly used for identification and security purposes and is claimed to be extremely accurate. Interestingly, when it comes to ageing, there have been numerous studies in which participants are asked to guess the age of individuals merely by looking at their photographs, with individuals looking older and others looking younger than their actual age.

There are various apps, such as developed by Google and Apple, available for your computer or smartphone which scan photographs of individuals and come up with an estimated age. There is also an app available which provides a projection of a younger or older you. A word of caution: choose your photographs carefully. A photograph of myself scanned at an estimated age of 87 and another, taken one month later, scanned at an estimated age of 52, although my chronological age is 78 and my personal age is 60.

Personal age may be defined as selecting an age at which you are most comfortable with and sticking to it. In reality, we were all born at a certain time on a precise day on a precise month in a precise year. This is your chronological age (CA). It is recognized in documents such as in your birth certificate, passport, driver’s license, tax file number, social security number etc and is required or at least requested by the myriad of government, internet and social media sites. There is simply no way of denying one’s CA.

On the positive or, in some cases, negative side, your CA may bear little relationship to age when we consider the concept of healthy ageing. If you have a positive outlook to life in general, you may consider yourself as younger than your CA; if you have a negative outlook you may consider yourself older than your CA.

What does the scientific methodology have to say about assigning your age? Surely, you say, there must be good scientific evidence that can accurately assign an age to individuals in relation to healthy ageing. After all, we have smartphones which are many more times powerful than the computers which successfully guided men to the Moon and back (1969), we have autonomous or driverless cars, we have radio telescopes which can ‘see’ almost to the beginning of time, we have the complete genetic code of the human DNA (genome) including the Neanderthals (and the chimpanzee, wooly mammoth and thousands of bacteria, fungi and viruses), and we have free Wi-Fi (well, in some places).

Thus, is there a scientific biomarker of ageing (BMA) that acts as a milestone as to one’s continual progress from birth to death, following a pathway towards healthy ageing? Biomarkers of ageing are not to be confused with biomarkers of disease. The latter is conceptually easier to envisage as in e.g. high blood glucose level/low insulin is indicative of type 2 diabetes, or a number of very specific markers of very specific diseases including some cancers. At this point in time, there is no single BMA but rather there are a number of biomarkers, which are indicative of healthy ageing. Biomarkers are further discussed in Chapter 2: Genes and Healthy Ageing.

A routine blood sample, say 20-30 ml, taken for an annual medical check-up, and sent to a pathology laboratory for common clinical tests can provide informative measures of an individual’s health status. The application of such analyses to predict an individual’s biological age (BA) as compared to CA has been reported in the scientific literature (Chapter 2: Genes and Healthy Ageing). A predictive BA is much more informative than CA with respect to overall health status and thus a measurable milestone towards healthy ageing. Moreover, the BA measurements should also include physiological, neurological and physical measurements. Physiological tests may include body mass index (BMI = weight kg/height m²), full blood count, liver function tests, lipid profile (HDL- and LDL- cholesterol, triglycerides) and C-reactive protein (as a measure of inflammation). Neurological tests may include cognitive function and physical measurements may include motor function (e.g. walking speed, balance, unipedal stance) and grip strength.

In a study of n = 954 individuals from the Dunedin Longitudinal Study (Belsky et al., 2015), researchers were able to assign individuals as ageing well (BA less that CA), ageing as per CA and ageing more rapidly (BA more than CA). The assessments were on the basis of a twelve-year follow-up of eighteen biomarkers of physiological status (initial age of participants was 37-38, all born in the same year in the same city, Dunedin, New Zealand). Importantly, measurements of neurological and physical parameters were consistent with the physiological tests in the assignment of BA. In another study of older cohorts (n = 9,389, mean age of 48, 50% female), comparing BA with CA in an eighteen-year follow-up it was concluded that BA, as measured by twenty-one biomarkers of physiological status, was a significantly more accurate predictor of mortality that CA (Levine, 2013).

We can conclude that the scientific consensus is that BA is a more accurate and thus useful measure of healthy ageing than CA.

A yearly check-up with your local physician is thus highly recommended as a key element in maintaining a healthy age profile. Your BA profile would also allow the identification of any lifestyle changes to be addressed should there be issues with parameters outside the expected norm. Early attention to these issues would certainly assist in the progress towards healthy ageing. Prevention or, at least, slowing down the rate of ageing is always better than cure; there is simply no cure for ageing. There is much publicity and hype regarding reversal or rejuvenation of human ageing, but it is just that, hype.

There is no substantive scientific evidence that supports the concept that we currently have the knowledge and capability of reversing human ageing. For example, cosmetic surgery and the hugely popular Botox treatments may have positive psychological effects as well as projecting a positive image of youthfulness and hence perception of CA. Nevertheless, BA is not likely to be greatly influenced and hence neither is one’s rate of ageing.

Does your DNA age? The simple answer is yes. As to the how, what and why, that is the mechanism of DNA ageing, a scientific researcher would say we need more data and, importantly, more funds to do more research on more individuals over a very long time frame. The scientific consensus is thus very much non-consensual.

However, there is agreement that DNA is subject to constant challenges as a result of everyday living associated with natural metabolic processes of eating and drinking. These metabolic processes generate chemical reactions some of which result in the formation of highly reactive molecules termed free radicals. Free radicals also result from the essential process of breathing oxygen (try not breathing for, say, five minutes to test the concept of essential; kids, don’t try this at home without adult supervision). The formation of highly reactive molecules via oxygen-related processes is, not surprisingly, called oxidative stress. Oxidative stress and free radicals are capable of damaging not only DNA but also proteins, lipids and carbohydrates. The concepts of oxidative stress and free radicals form the cornerstone of the free radical theory of ageing, first postulated by Denham Harman (Harman,1956).

It is now universally recognized that DNA is also subject to lifestyle and environmental stressors, which impinge on DNA structure and function. These stressors include financial and social stressors, exercise, smoking and alcohol. These stressors have profound effects on DNA and greatly influence healthy ageing. Parts of your DNA that you inherited from your parents are thus not fixed throughout your life but are dynamic and modulate as a function of your lifestyle and environment.

Research in the past few decades has demonstrated significant DNA modifications with age. The two most studied DNA modifications associated with ageing, are the telomeric age and the epigenetic age, both of which have been proposed as biomarkers of ageing. Importantly, the telomeric age and epigenetic age modulate not only with age but also are subject to alteration by lifestyle and environment. The telomeric age and epigenetic age in relation to healthy ageing is discussed in Chapter 2: Genes and Healthy Ageing.

There are a number of inconvenient questions to be raised in the context of healthy ageing. These questions are at the core of our understanding or lack of understanding of issues which are the elephant in the room in that these issues are to be conveniently avoided as they do not fit the established way of thinking and indeed, in most cases, also the general public’s view of healthy ageing. However, to have any appreciation or understanding of healthy ageing we must address these issues in a non-biased way.

1.Telomeric DNA (DNA sequences at the end of chromosomes) has been proposed as a key marker of ageing with maintenance of telomere DNA length as a key biomarker of healthy ageing. How is it then that there is clear scientific evidence that cells that maintain long telomeres have a high probability of attaining the cancerous state and that healthy centenarians have relatively short telomeres? (Chapter 2 Genes and Healthy Ageing: A Beginner’s Guide to DNA).

2.The Dietary Guidelines for Americans, based on the very best available scientific data, have been issued every five years since 1980, the latest is the 2015-2020 edition. How is it then that overweight and obesity in the developed and increasingly also in the developing nations have rapidly increased in the past thirty years? (Chapter 3 Nutrition 101: What Are the Facts on Fats and Sugars?).

3.Fats, especially saturated fats, have been implicated as a, if not the, major culprit in the obesity epidemic. How is it then that there is no, and has never been, substantive scientific data that actually provides evidence that consumption of foods (e.g. dairy) containing saturated fats leads to weight gain? (Chapter 3 Nutrition 101: What Are the Facts on Fats and Sugars?).

4.After decades of scientific research, supported by many millions of dollars of funding, by some of the world’s most distinguished scientists in some of the world’s most distinguished universities, the consensus has now been reached that highly processed packaged foods may not be that good for one’s health. How is it then that your grandmother, with limited financial support, came to that exact same conclusion many, many years ago? (Chapter 3 Nutrition 101: What Are the Facts on Fats and Sugars?).

5.The Mediterranean diet has been universally praised as the diet for successful health and healthy ageing. How is it then that individuals living in countries (e.g. Greece, Italy, Spain) that traditionally follow a Mediterranean diet do not live any longer or, importantly, do not have a longer healthy lifespan than individuals who live in countries (e.g. U.K., Canada, Australia) that do not follow the Mediterranean diet? (Chapter 4 Diets and Dietary Supplements: The Truth, the Whole Truth and Nothing but the Science).

6.It has been well documented, ever since the original observations in 1935, in the most highly ranked scientific journals that food restriction (termed calorie restriction) leads to a substantially longer life in the flagship animal model for ageing research, the rodent. How is it then that calorie restriction is most unlikely to be a key aspect of healthy ageing in humans? (Chapter 4 Diets and Dietary Supplements: The Truth, the Whole Truth and Nothing but the Science).

7.It is conservatively estimated that 50% of the adult population, especially women, in the USA and Europe takes dietary supplements such as herbal and vitamin supplements in the belief that they would enhance one’s health and thus lead to healthy ageing. How is it then that there is little or no scientific evidence that these supplements have any beneficial health effects? (Chapter 4 Diets and Dietary Supplements: The Truth, the Whole Truth and Nothing but the Science).

8.It has been estimated that, at any given time, 30% to 40% of the population in the developed world is on some kind of weight-loss diet. How is it then that all the evidence clearly shows that in the long-term (> one year) weight-loss diets simply do not work for the great majority of individuals? (Chapter 4 Diets and Dietary Supplements: The Truth, the Whole Truth and Nothing but the Science).

9.It is well established that excess consumption of alcohol or coffee has negative effects on health. How is it then that data in prestigious scientific journals have consistently reported health benefits of moderate alcohol or coffee consumption? (Chapter 5: Alcohol and Coffee: Drinking to Your Healthy Ageing).

10.It has been frequently reported in leading scientific and health related publications that exercise adds years to one’s life, with estimates that regular exercise can add around two years to one’s life. How is it then that if you exercise one hour every day for fifty years this equates to almost exactly two years? (Chapter 6 Physical Activity: Keep Calm and Walk the Dog).

11.In the past decade or so, a major recognition has been the demonstration that our microbiota (microbes that inhabit on and in our bodies) plays an absolutely essential role and has profound effects on our health and thus healthy ageing. How is it then that the general public has no concept and little knowledge that microbes are essential for life and our well-being? (Chapter 7 Your Gut Microbiota: It’s a Small World After All).

Each of these questions will be addressed in the indicated Chapters in this book. Maximum benefit will be obtained on these and other topics on healthy ageing when one approaches these issues from a non-biased and informed viewpoint.

Bias is the tendency, either conscientiously or unconscientiously, to look at and absorb information that supports your biases (i.e. preconceived conclusions) and ignores, again conscientiously or unconscientiously, those that are against your biases. Discussions or arguments, and there are many disagreements as to the nature of healthy ageing, that are one-sided are perceived to be superior to those that present other sides of the argument.

We see what we are looking for and search for confirming evidence or selective findings for our biased views, termed confirmation bias or personal truths. In other words, we may place a very high weighting on one piece of evidence supportive of a biased view and ignore or apply a very low weighting on evidence that does not agree with one’s biased view. Of course, one should have confidence in one’s judgmental ability to make a conclusion or decision. On the other hand, overconfidence may lead to overlooking important alternative aspects of one’s conclusions. It is relatively easy to find fault with other peoples’ beliefs but extremely difficult to find fault with one’s own beliefs.

It is most important to recognize that we are all inherently biased. Your biases are part of your personality that has been moulded by your life experiences and interactions with family, friends and colleagues, and even influenced by your environment. Consider the weather. On a wet, cold, dark winter day, you are biased towards a certain conclusion or belief. Now consider the same conclusion or belief on a warm, sunny summer day in a pleasant and relaxed atmosphere such as having a coffee at your favourite cafe. Or try the same belief after a stressful day at work. In fact, reading this book and selected Chapters, in different environments (ideally reading the same Chapter say a month or two later but in a different environment) will very likely influence your judgement and hence biases.

A recent publication in the journal Scientific Reports (Seresinhe et al., 2019) concluded that individuals are more likely to have positive thoughts in scenic environments, and not only in natural environments but also in built-up areas.

Anecdotal evidence (translation: some years ago, I read an article in a reputable newspaper and recall some of the details) suggests that in a real democracy (and including only individuals who actually bother