Over the last 200 years, human life expectancy has nearly doubled. Demographic data confirm that at the beginning of the nineteenth century, a child born could only expect a short life, considering that globally, no country had a life expectancy more than 40 years. In the United Kingdom (UK), for instance, the country with the longest time‐series, in 1765, a baby girl was expected to live up to 42 years and a boy to 40. In 2019, life expectancy was 83 and 79 years old for women and men, respectively (Roser, Ortiz‐Ospina, Ritchie, 2019). In the 150 years since 1765, some parts of the world experienced great improvements in life expectancy. This shift was mainly related to a significant reduction in early life mortality observed during the first half of the twentieth century, followed by an almost twofold reduction in mortality at ages 70 years and older in the past 50 years (Oeppen & Vaupel, 2002) (Figure 8.1). Worldwide, according to the United Nations (UN), the mean life span over the last few decades, has increased from 52.5 in the 1960s, to 73 years old today (The World Bank group, 2021) (Figure 8.2). However, since the 1950s, increases in life expectancy have slowed, demonstrating that human life expectancy might have reached its biological upper limit (Cardona & Bishai, 2018). Similarly, the maximum life span has only modestly increased too. These observations prompted the notion that the human life span might have reached its maximal natural limit of about 115 years (Brooks‐Wilson, 2013). The oldest documented person in the world to date, lived to 122 (Robine & Allard, 1998). Others argue that the lack of increase does not exclude the possibility that the maximum human life span might increase in the future. These observations make us wonder: is our life span flexible or fixed by genetics? Although the human life span is prolonged, there is no evidence to suggest that older people are experiencing better health than their ancestors at the same age (Calder et al., 2018). It is true that the healthy life expectancy has increased around the world in recent decades, though it is also a fact that improved healthcare increased the number of years experiencing disease or disability; as people age, they have an increased risk for disease and disability (Figure 8.3). Aging was described as an accumulation of the impact of time, environmental factors, and disease (Bussee, 1969). Notably, older people have a higher incidence of cerebrovascular and ischemic heart disease, chronic obstructive lung disease, dementia, vision disorders, and cancer (Byles, 2007). These conditions apparently contribute to a great loss of years and significantly affect quality of life. Considering that increases in lifespan exceed increases in health span, an important question arises about how people can live longer and healthier lives. Modern medical research focuses mostly on learning the causes of disease pathology, noting that disease is the major challenge to tackle. For some this pathology‐oriented approach for prevention and treatment, the so‐called “negative” biology, might be the wrong way to evaluate human health (Farrelly, 2012). Rather than examining what causes disease and disability, emphasizing what causes ideal health and happiness might be a priority and possibly an alternative question to answer. “Positive” biology strives to understand positive phenotypes: why some individuals live a longer and healthier life, without suffering from the diseases that most people confront much earlier in their lives. Observations of exceptional longevity (reserved for individuals aged 100 years or more, otherwise known as centenarians) might provide insights about how to obtain exemplar health and well‐being; centenarians might represent an ideal healthy aging model. Undoubtedly, the basis of human longevity and healthy aging that constitute the “positive” aging and how to conquer these desirable phenotypes are a scientific milestone (Brooks‐Wilson, 2013). FIGURE 8.1 Life expectancy, 1543 to 2015. Source: (Riley, 2005). FIGURE 8.2 Life expectancy by region, 1950 to 2050. UN World Population Prospects, 2017. Source: (Adapted from Roser, 2019). FIGURE 8.3 Worldwide healthy life expectancy and years lived with disability, 1990 to 2016. Source: (The World Bank Group, 2021). Human longevity is often defined as reaching an age of ≥85 years, but a single accepted definition does not currently exist (Murabito, Yuan, & Lunetta, 2012). Worldwide demographic data reveal that the oldest older adults, usually defined as individuals over 85‐years old, are the fastest growing population group (Ritchie & Roser, 2019). As global health improves and mortality falls, people are expected to live longer than before. Consequently, the proportion of older people will substantially expand, and considering that the number of children will barely increase, for the first time in history there are more people over 60 than children under 5. The number of children under 5‐years old is projected to peak and plateau for most of the twenty‐first century, and as the global population of older people will continue to grow, it seems that we are moving toward an aging world. Due to this demographic change, the UN Global Population Pyramid is undergoing a major change from the classical shape of a pyramid to a cube (Panagiotakos et al., 2011). Indeed, nonagenarians and centenarians are expanding in many countries. For instance, in Japan, the number was estimated to increase from 154 in 1963 to 36,276 in 2008 (Robine, Saito, & Jagger, 2003), a 235‐fold increase in less than 50 years. The US Census bureau predicts that 834,000 centenarians will exist in the United States by the year 2050 (Velkoff, 2000). Japan, followed by Germany, Italy, Greece, Finland, and Sweden had the world’s oldest populations in 2015, and by 2050, some other Asian populations, including South Korea, Hong Kong, and Taiwan are expected to experience a longevity boom (United States Census Bureau, 2015). In 2015, Japan, Macau, Singapore, Australia, and Switzerland had the longest life expectancy at 65, with an additional 25.2 and 20 years of life for Japanese women and men, respectively. It is noticeable that among the long‐lived countries, healthy life years vary between 25% and 75% of the predicted life expectancy at 65 years old, with Norway, Sweden, and Iceland having the greatest number of expected healthy years at age 65 (Sebastiani & Perls, 2012). It is important to mention that globally, women live longer than men and account for a larger proportion of the older population, especially at exceptionally old ages. To illustrate this in the US, 1% of women born during the end of the last century lived to be 100, whereas the same percentage of men was 0.1% (Sebastiani & Perls, 2012). Furthermore, among the original 5,209 Framingham heart study participants with follow‐up through 2011, there were 43 centenarian women and only 6 centenarian men. Nevertheless, men are more likely to reach extreme old age while escaping common age‐related diseases, whereas women are more likely to attain 100 after surviving common morbidities (Evert, Lawler, Bogan, & Perls, 2003). Therein lies a paradox of women’s survival advantage: They suffer from more illness and chronic health problems than men but die at lower rates from all the major causes of death (Austad & Bartke, 2015). The Williams evolutionary hypothesis says that the sex subjected to the greatest extrinsic hazards in the wild will evolve the more rapidly deteriorating phenotype. From this perspective, it seems that women are the superior survivors when they are old, young, and even in utero. Possible confounders that explain these sex discrepancies might include hormonal and immune differences as well as hemizygosity of the X‐chromosome in men, among others (Brooks‐Wilson, 2013). There are places around the world where people live longer and probably share common behavioral and lifestyle characteristics like “family coherence, avoidance of smoking, plant‐based diet, moderate and daily physical activity, social engagement, where people of all ages are socially active and integrated into the community” (“The Blue Zones”, 2010). These places are defined as the “blue zones” and are a part of a large anthropologic and demographic project. More specifically, people living in Sardinia (Italy), Okinawa (Japan), Loma Linda (California), Nicoya Peninsula (Costa Rica), and Ikaria (Greece) have extremely high life expectancy, with amazing rates of people over the age of 90 compared with the average rate of high‐income countries. What makes these populations so special? Long‐lived Okinawans eat a rainbow diet, based on diverse fruits and vegetables, and their daily caloric intake is substantially decreased, accounting for their low body‐mass index. Additionally, Sardinian men, compared with men elsewhere, tend to live longer due to genetics as well as small, apportioned meals, hand‐work, and red wine. Seventh Day Adventists, a religious community residing in Loma Linda, California, are strict vegetarians, abstain from tobacco and alcohol, and exhibit significantly lower levels of stress hormones that is closely related to the weekly break from the rigors of daily life, the 24‐hour Sabbath. Adventists claim this provides a time to focus on family, God and relieves their stress. The Costa Rican Nicoyan diet is based on beans and corn tortillas, people regularly perform physical jobs into old age, and have a sense of life purpose known as “plan de vida” (reason to live). Moreover, Ikarians in Greece are almost entirely free of dementia and some of the chronic diseases that affect Western communities; one in three make it to their 90s. They enjoy red wine and a relaxed pace of life that ignores clocks. Blue Zones is a way to design the healthiest lifestyles possible for individuals and for entire communities. Over the past two decades research efforts focus on the factors associated with blue zones longevity, as well as exploring the possibility of lessons transferable to the general population (Buettner, & Skemp, 2016). Although their lifestyles differ slightly, they mostly eat a plant‐based diet, exercise regularly, drink moderate amounts of alcohol, get enough sleep and have good spiritual, family and social networks. Probably, a combination of factors explains it, including geography, culture, diet, lifestyle, and a positive outlook (Pignolo, 2019; “The Blue Zones”, 2010). Along with the prolonged lifespan observed in most high‐income countries, there is a growing concern about the quality of life in those living beyond 70s as well as whether the added years will be counterbalanced by increased morbidity and disability at older ages. Although amplify data indicate that lifetime medical expenses for care do not further increase at incredibly old ages, long‐term care costs increase since most older adults need some form of assistance with activities of daily living (Christensen, McGue, Petersen, Jeune, & Vaupel, 2008). Consequently, questions remain whether these added years are offset by increased morbidity and disability at older ages. Therefore, it is extremely important to identify and closely examine the factors that allow long‐lived individuals to be healthy and independent until the end of their lives. There is a long debate within gerontology as to whether longer life is associated with a “compression of morbidity” or an “expansion of morbidity”. According to Gruenberg (Gruenberg, 2005), the treatment of acute illnesses and the management of chronic diseases equate to living more and more frail. The theory of “failure of success” advocated that prolonging life span will prolong disease and disability. At the same theory it was argued that “the net effect of successful technical innovations used in disease control has been to raise the prevalence of certain diseases and disabilities by prolonging their average duration”. Similarly, the “expansion of morbidity” advocates a pessimistic view of trading longer life with healthier years, foreseeing an increase in life expectancy through medical advances with an increase in the proportion of life spent with an underlying illness or disability (Olshansky, Rudberg, Carnes, Cassel, & Brody, 1991). People will live longer (due to reduced mortality) but with increased morbidity and duration of morbidity. On the contrary, the “compression of morbidity” theory (Fries, 1980) states that “the burden of lifetime illness may be compressed into a shorter period before the time of death if the age of onset of the first chronic infirmity can be postponed” (Figure 8.4). The compression of morbidity theory was introduced as a hypothesis of healthy aging in 1980 and advocated that “the age at first appearance of symptoms of aging and chronic disease can increase more rapidly than life expectancy.” In this optimistic view, changes in lifestyle can modify the risk factors for mortality and postpone the onset of morbidity. Additionally, this hypothesis strongly suggests that the net effect of primary prevention is to reduce and compress disability into a shorter period toward the end of life, decrease overall lifetime disability, and consequently, reduce the associated health care burden (Fries, Bruce, & Chakravarty, 2011). Based on these considerations, Manton tried to bridge the gap by developing a third theory of population health change, the “dynamic equilibrium” (Manton, 1982), which is an intermediate scenario that combines the first two hypotheses: the compression and expansion hypotheses. Manton suggested an increase of life expectancy along with a constant proportion of healthy lifespan and a decrease in the severity of diseases and disabilities over time. According to this notion, the dynamic equilibrium scenario implies that “mortality reductions are at least partially, the result of reductions in the rate of chronic disease progression and is associated with a redistribution of disease and disability from more to less severe states”. Regarding this possibility, the period of life span with serious illness or disability remains constant, whereas the time period with moderate disability or less severe illness increases. FIGURE 8.4 The compression of morbidity theory. Scenarios for future morbidity. The three major population scenarios in the upper part of the figure represent (i) depiction of a present health, (ii) a future where both life expectancy and morbidity are increased, and (iii) a future where both the time period after first morbidity and the amount of morbidity are decreased, resulting in compression of morbidity. Shaded areas under the curve represent cumulative morbidity. Source: (Fries et al., 2011 / Hindawi / CC BY‐3.0). Over time, the likelihood of living to 100 rose from 1 in 20 million, to 1 in 50 for women in low‐mortality countries, like Japan and Sweden (Pignolo, 2019). A study of centenarians (individuals aged of 100–104 years), semisupercentenarians (105–109 years), and supercentenaians (110–119 years) found that the older the age group, the greater the delay in the onset of age‐related diseases (Velkoff, 2000). Lifespan and health span seem to be strongly related and individuals who live long tend to be healthier during their lives. Longevity and healthy aging are extremely complex characteristics that entail the maintenance of long‐term function and disease absence or reduction (Brooks‐Wilson, 2013). There lies the question. Why are some individuals long lived? What is so special about them? Observations of centenarians might give insight into why some people enjoy a long life and most of all, a life in good health. Centenarians are generally considered a healthy aging model (Puca, Spinelli, Accardi, Villa, & Caruso, 2018). They have reduced mortality rates and are less prone to the diseases that come with aging. Some are even disease free, the so‐called “escapers”, while others, the “survivors” from diseases in earlier life, are frailer. Although research data indicate that 1% of Italian centenarians, for instance, are fully independent whereas 2% of the Japanese centenarians are in perfect health, defined as having no sensory problems, cognitive defects, and being independent, numerous studies suggest that centenarians were in a relatively good health 5 or 10 years previously (Robine et al., 2003). In the 1905 Danish cohort, the vast majority of those who became 100‐years old in 2005, were physically independent at 92‐years old, indicating only a modest decline in independent individuals’ ratio between ages of 92 and 100. Additionally, individuals who survived into the highest ages had a health profile like that of individuals who were 7 or 8 years younger (Christensen et al., 2008). Whether centenarians constitute a healthy aging prototype is an area of debate, however, living up to 100, 20 to 25 years more than the average person, is astonishing. Centenarians may represent a unique cluster for examining the genetics of the extremely long lived as well as the interaction between genes and the environment. Data from longitudinal studies reveal that centenarians were healthier than their coevals who died at younger age (Puca et al., 2018). Danish centenarians from the 1905 birth cohort study experienced fewer hospitalizations and fewer hospital days than their shorter‐lived contemporaries (Engberg, Oksuzyan, Jeune, Vaupel, & Christensen, 2009). This observation might reveal two important parameters of health in the oldest older adults. First, centenarians seem to postpone critical disease into their later years of life, and second, the diseases and morbidities that centenarians suffer may be less severe or influence them to a lesser extent. It is well documented that both genetics and environmental, lifestyle factors affect survival. To make it to age 100, it seems that a person must win the genetic lottery. Cumulative data indicate that to live to 100, one must inherit the right genetic variants from parents or acquire epigenetic variants through the environment (Murabito et al., 2012; Passarino, de Rango, and Montesanto, 2016). Apparently, it is strongly stated that genes affect living till old age. Longevity as well as healthy aging are highly clustered within families, but this clustering can be excluded by chance (Brooks‐Wilson, 2013
CHAPTER 8
The Interface Between Healthy Aging, Longevity, and Disease
INTRODUCTION
OVERVIEW OF LONGEVITY
THE LONGEVITY BOOM
SEX DIFFERENCES
GEOGRAPHICAL LONGEVITY CLUSTERS
OVERVIEW OF THE CONCEPTS OF MORBIDITY AND MORTALITY
LONGEVITY AS A HEALTHY AGING MODEL
ARE THE LONG LIVED, HEALTHY LIVED?
THE HERITABILITY OF LONGEVITY AND HEALTHY AGING
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