Human Aging: From Cellular Mechanisms to Therapeutic Strategies

Human Aging: From Cellular Mechanisms to Therapeutic Strategies offers an exhaustive picture of all the biological aspects of human aging by describing the key mechanisms associated with human aging and covering events that could disrupt the normal course of aging. Each chapter includes a summary of the salient points covered, along with futures prospects. The book provides readers with the information they need to gain or deepen the skills needed to evaluate the mechanisms of aging and age-related diseases and to monitor the effectiveness of therapies aimed at slowing aging.

The book encourages PhD and Postdoc students, researchers, health professionals and others interested in the biology of aging to explore the fascinating and challenging questions about why and how we age as well as what can and cannot be done about it.

• Concentrates on different processes, e.g., oxidative stress, cellular senescence and Inflammaging
• Offers the ability to access cross-sectional knowledge more easily
• Written by expert researchers in biogerontology who are actively involved in various fields within aging research

• Language: English
• Publisher: Academic Press
• Release date: May 11, 2021
• ISBN: 9780128227374

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Preface

Calogero Caruso; Giuseppina Candore

The extraordinary increase in older people underlines the importance of studies on aging and the need for a prompt dissemination of knowledge on aging in order to satisfactorily diminish the medical, economic, and social problems associated with advancing years, problems caused by the continuous increase in the number of older people at risk of frailty and age-related diseases. Hence, improving the quality of life of older people is becoming a priority. This makes the studies of the processes involved in aging of great importance.

Human Aging: From Cellular Mechanisms to Therapeutic Strategies, written by expert researchers in biogerontology who are actively involved in various fields within aging research, offers an exhaustive picture of all the biological aspects of human aging by describing the key mechanisms associated with human aging. Each chapter includes a summary of the salient points covered and future perspectives. The book provides readers with the information they need to acquire or deepen the skills needed to assess the mechanisms of aging and age-related diseases and to monitor the effectiveness of therapies aimed at slowing aging. Reading this book will inspire PhD and postdoc students, researchers, health professionals, and all other figures interested in the biology of aging to explore the fascinating and challenging questions about why and how we age and what can and cannot do about it.

A long life in a healthy, vigorous, and young body has always been one of humanity’s greatest dreams. Antiaging strategies aimed not at rejuvenating but at slowing aging and delaying or avoiding the onset of age-related diseases are discussed in the book. It is emphasized that the goal of aging research is not to increase human longevity regardless of the consequences, but to increase active life free from disability and functional dependence.

Chapter 1: Aging and longevity: An evolutionary approach

Giuseppina Candore; Calogero Caruso    Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy

Abstract

In the chapter, first of all, the definition of aging, longevity, and the various types of aging are discussed. Then, analyzing various theories of aging, it is recalled how evolution teaches us that there should be no genes selected to promote aging. Aging is not planned but derives from the accumulation of physical damage, due to limited investments in maintenance and repair as well as from the epigenetic changes. After sufficient time has passed, the increasing levels of these defects interfere with the performance of tissues and organs, resulting in a breakdown of self-organizing system and a reduced ability to adapt to the environment.

Keywords

Aging; Demographics; Longevity; Genetic programs; Genetic regulation; Anthropological

1.1: Introduction

Aging is most likely a component of life, which first emerged in economically developed countries and results from the disruption of self-organizing system and reduced ability to adapt to the environment. It is an inescapable natural phenomenon, which affects all cells, tissues, organs, and organisms. As people age, detrimental changes accumulate at the level of molecules, cells, and tissues responsible for the decline in normal physiological functions. That leads inexorably to a reduced ability of the individual to maintain adequate homeostasis, determining a greater susceptibility toward different kinds of stressors (Avery et al., 2014).

Aging processes are defined as those that amplify the vulnerability of individuals, as they age, to the factors that ultimately lead to death (Fig. 1.1, Table 1.1). An emerging concept is the difference between chronological and biological aging; the cells, tissues, and organs of the same individual may have a different rate of aging in contrast to the chronological age. Conversely, individuals with the same chronological age may have a different aging rate and a different biological age (Avery et al., 2014).

Fig. 1.1

Fig. 1.1 Semi-log graph of mortality rates by age. As described by Gompertz, mortality rates increase exponentially with age with a doubling of mortality in adult life every eight years. At older age, the rate slows down, as indicated by the plateau of the curve. This phenomenon has been called demographic selection. The age is indicated on the abscissa, while the mortality rate log is shown in the ordinate.

Table 1.1

As for the term longevity, based on the demographics, longevity can be defined in relative and absolute terms. The term relative suggests that longevity must take into account the life expectancy of different populations that show great variability due to historical, anthropological, and socioeconomic factors. Thus, long-lived individuals refer to people belonging to the 5 percentile of the survival curve, that is, in the Western world, to those over ninety. In absolute terms, longevity could be defined according to the maximum life span attained and scientifically validated by human beings (Avery et al., 2014; Villa et al., 2019).

Aging is considered a multifactorial process that does not recognize a single responsible cause, but which is, rather, the result of numerous mechanisms that interact simultaneously at different levels. Many variables contribute to aging and longevity such as cultural, anthropological, and socioeconomic status; as well as gender and sex, women live longer than men (Caruso, 2019); and ethnic differences, explained by discrepancies in health; environmental and economic condition; education, genetics, and kinds of job; as well as epigenetics and stochastic events (Accardi et al., 2019).

These variables also contribute to different kinds of aging, i.e., successful or unsuccessful aging. Although there is no universally accepted definition of successful aging, one can refer to the World Health Organization definition, that is, the process of developing and maintaining functional ability that enables well-being in older age. Some criteria have been developed that describe it. They include three main related components, i.e., low probability of developing disease-related diseases and disabilities, high cognitive and physical functional capacity, and active engagement with life. The combination of these components guarantees an active end of life that is the essential concept of successful aging. Reciprocally, the presence of age-related disease and disability, low cognitive and physical functional capacity, and reduced engagement with life should characterize unsuccessful aging (Bülow and Söderqvist, 2014; Aiello et al., 2019b).

Aging is generally thought to be a universal biological phenomenon that affects all living things, although prokaryotic kingdom seems to be not involved. The bacteria, in fact, divide in a symmetrical way, generating by division two identical individuals that do not seem to bear the signs of aging. The aging process therefore appears to be a characteristic of the eukaryotic kingdom. Brewer's yeast, Saccharomyces cerevisiae, one of the simplest single-cell organisms, splits by budding. At the end of the reproductive process, a parent cell can be identified, which has a maximum limit of cell divisions, and which progressively accumulates damages and loss of functions until death, i.e., it ages (Kaeberlein et al., 2007). In the gradual progress of the evolutionary scale, a greater complexity of the mechanisms regulating organism homeostasis is observed and, in parallel, also of those that cause a progressive deterioration.

Unlike what happens in single-cell organisms, in animals, in addition to a first level of cellular organization, there is a second organizational level, which is achieved through the regulation and modulation of the immune, endocrine, and nervous systems. Some studies on the biology of aging point out the prevalent role of systemic factors in the causes of aging, other studies promote the idea that the intrinsic changes that take place at the cell level are at the origin of aging (Zhang et al., 2013; Phillip et al., 2015). Probably, both conditions act simultaneously, and if the intrinsic cellular mechanisms are fundamental, their activation is closely regulated by extracellular factors, such as hormones, immune-inflammatory responses, and lifestyle.

1.2: Why does aging occur?

One question commonly arises: Why does aging occur? Aging from a biological point of view still remains a largely mysterious process. Over the years, various theories have been developed to attempt to explain the mechanisms that trigger and guide aging (more than 300 have been listed). As a consequence of the lack of adequate models for the study of human aging, and the frequent inability to distinguish between causes and effects, currently there is no general consensus on what causes aging, what determines the variability of longevity between species, what happens to a human being between 30 and 70 years of age who is responsible for the 30-fold increase in risk of death (Troen, 2003). In general, all theories tend toward two main lines of thought, the possibility of programmed aging, which triggers aging processes like a biological clock, and that of aging due to damage accumulated during life, which, over time, overwhelms repair capacities.

Old animals are practically not found in nature, but only in zoos and among domesticated species such as dogs and cats that are no longer prey or predators. There is the exception of elephants and turtles that can live very long, because for intuitive reasons they are not an easy prey. Since aging has a negligible impact on organisms in their natural environment due to predation, malnutrition, accidents, diseases, exposure to the elements, two corollaries can be immediately deduced; aging is not a genetically programmed event to control the size of the population (see later for the discussion of this point); the selection cannot exert a direct influence on the aging process.

In fact, nothing in biology makes sense except in light of evolution (Dobzhansky, 1973); therefore, we must try to frame the aging process in the context of the evolutionary limitations imposed by natural selection, in light of Darwinian medicine.

Aging theories can be grouped into two main groups, the first represented by the group of genetically programmed, the second by the group of error theories or stochastic. The genetically programmed theories consider aging as an event completely dependent on the biological clock, which regulates life expectancy through the fundamental stages of an individual life, such as growth, development, maturity, and old age. This regulation would depend on genes capable of inducing sequentially and regulated changes in the activation or inhibition signals of the various systems, responsible for maintaining homeostasis, triggering the various responses. Several researchers are attracted by the idea of the existence of a genetic program. It is hypothesized that aging (and consequent death) is necessary, either to prevent the overcrowding of the species environment or to promote evolutionary changes by accelerating the turnover of generations. This idea was proposed as early as 1891 by Weismann (References in Kowald and Kirkwood, 2016). Today, however, we know that the group selection on which this idea is based is much weaker than the selection at the individual level (Maynard Smith, 1976). A strong objection to the idea that aging is driven by a genetic program is the empirical finding that all model studies have never led to the discovery of gene mutations that abolish the aging process (Kirkwood and Melov, 2011). If such genes exist, as implicit in programmed aging, they would in fact be susceptible to inactivation by mutation. However, older age is not an adaptive phenomenon, it cannot be selected by evolution, because the selective pressure acts only on the characters that favor the reproduction of the species and cannot act toward the characters concerning the postreproductive life. In fact, human subjects and animals are selected in such a way as to guarantee survival until reproduction.

The theories of error or damage identify environmental insults within living organisms capable of inducing progressive damage at various levels. The best known is the free radical theory. It has greatly attracted scientific attention, presenting itself as a possible biological explanation of the entire aging process. This process, modifiable by genetic and environmental factors, is characterized by the accumulation of free oxygen radicals (ROS), which damage all biological molecules, causing, over time, a vicious circle. In fact, that causes, in turn, damage of mitochondrial DNA (mtDNA) as well as of the proteins of the electronic transport with a consequent increase in the production of ROS. ROS, exceeding the endogenous buffering capacities, are the cause of genotoxic damage, capable of eventually inducing cell senescence or apoptosis (Harman, 2003). Free radicals are implicated in the development of most age-related diseases, resulting in unsuccessful aging (Chapter 3). However, their significance in physiological aging remains unclear, mainly due to the limited effect, demonstrated in various animal models, of antioxidant systems in extending life span (Chapter 6).

Alternatively, the explanation for why aging occurs is thought to be found among three ideas all based on the principle that natural selection decreases during adult life (Medawar, 1952). There remains, therefore, only the explanation that the aging process is linked to the decreasing force of natural selection with chronological age, as recognized in 1952 by Medawar. This decline occurs because in progressively older age, the fraction of total future reproductive production, on which selection can act to discriminate between more suitable and less suitable genotypes, becomes progressively smaller.

The three evolutionary theories based on this insight, mutation accumulation (Medawar, 1952), antagonistic pleiotropy (Williams, 1957), and disposable soma (Kirkwood, 1977) are not mutually exclusive, but can be easily integrated. The theory of the accumulation of mutations (Medawar, 1952) assumes that over time there is a constant generation of deleterious mutations that, therefore, are expressed only after a certain age when the natural selection process will not be more efficient.

Williams (1957) suggests that a gene that has a benefit early in life, but is harmful later in life, may overall have a net positive effect and will be actively selected. Genes useful in the early stages of life such as, for example, those responsible for a powerful inflammatory response that protects against infections, become harmful in the late stages of postreproductive life and therefore not subjected to selective processes, as they are responsible for age-related inflammatory diseases. The immunoinflammatory responses represent typical adaptive responses resulting from evolutionary compromises. They represent in the modern world, cleaner from a microbial point of view, than in the past, the possible cause of allergic or autoimmune diseases or inflammatory diseases associated with old age. They are neither defensive nor pathological answers; they are teleonomic answers (Licastro et al., 2005).

The disposable soma theory (Kirkwood, 1977) is concerned with optimizing the allocation of resources between maintenance on the one hand and other processes such as growth and reproduction on the other. An organism that invests a larger fraction of its energy budget in preventing the accumulation of damage to its molecules, cells, and organs will have a slower aging rate, but will also have fewer resources available for growth and reproduction, and vice versa (Kirkwood, 2008). The theory of disposable soma adds a mechanistic specificity to the other two evolutionary theories of aging, which had previously been elaborated considering that the strength of natural selection tends to progressively reduce the effects of genes with age. The theory clearly emphasizes that aging is mainly driven by the impact, over the course of life, of molecular damages accumulated in cells. Aging appears as a process characterized, in its natural course, by the accumulation of damage from the early stages of life. The harmful events are completely random, as they affect a wide spectrum of targets within the cell. The rates at which they manifest and repair themselves are to some extent regulated through the evolutionary selection of the cellular machinery that serves macromolecular biosynthesis and repair (Kowald and Kirkwood, 2016). It is from the genetic specificity of certain mechanisms and from their level of functioning that the degree of heritability of longevity derives. The aging process clearly reveals how a variety of nongenetic factors can act to influence age-related morbidity and mortality. These factors include education, nutrition, lifestyle, socioeconomic status, sex and gender, and job.

1.3: Mechanisms of aging

Several studies have reported an age-related increase in somatic mutations and other forms of DNA damage, suggesting that DNA repair capacity plays a key role in cellular and molecular aging rates. When comparing species with different rates of longevity, it was found that there is a general relationship between longevity and DNA repair. The evidence for it is further strengthened by the accelerated aging phenotypes of DNA repair mice mutants and human progeroid syndromes (Hasty et al., 2003; Vijg and Suh, 2013; Oshima et al., 2018).

An important relationship between molecular stress and aging is given by the accumulation of mutations of mtDNA with increasing age. Cells in which mtDNA mutations are numerous are likely to produce reduced amounts of ATP with consequent decrease in tissue bioenergenesis, with therefore less energy available for maintenance and repair systems (Cui et al., 2012).

In addition to DNA, proteins are also prone to damage. The exchange of proteins is essential to preserve cellular functions, removing damaged proteins. Age-related impairment of protein turnover is evidenced by the accumulation of damaged proteins over time, which contributes to a wide range of age-related diseases, including cataracts, Alzheimer's disease, and Parkinson's disease. Protein exchange involves the chaperonins involved in the sequestration and wrapping (folding) of denatured proteins and the proteasomes involved in the recognition and degradation of damaged proteins. With aging, a functional decline in the activity of proteasomes and chaperonins as well as autophagy has been demonstrated. These functional reductions may be part of a more general malfunction, due to overloading, of the waste disposal cellular processes (Reeg and Grune, 2015; Vilchez et al., 2014; Barbosa et al., 2019).

Most researchers are convinced that age-related changes are characterized by an increase in entropy. This hypothesis is now supported by the reinterpretation of the Second Law of Thermodynamics, which would not apply only to closed systems. The entropy increase results in a random loss of molecular fidelity (Table 1.2) and builds up to slowly overwhelm maintenance systems. Entropy can be defined as the tendency of concentrated energy to disperse when it is not hindered. In biological systems, the hindrance is the relative strength of chemical bonds. In fact, preventing the breakdown of the chemical bond is absolutely essential for life. Natural selection has favored energy states that can maintain fidelity in most molecules until reproductive maturity, after which there is no species survival value for those energy states to be maintained indefinitely. The dispersion of energy can result in a biologically inactive or malfunctioning molecules (Hayflick, 2007a,b).

Table 1.2

Energy dispersal is never completely eliminated but can be buffered for some time by repair or replacement processes. After reproductive maturation, this balance slowly shifts into one where molecules that lose their biologically active energy states are less likely to be replaced or repaired. The aging process occurs because the change of energy states of the biomolecules makes them malfunctioning or inactive. Identical events obviously occur before the appearance of the aging phenotype, but the repair and replacement processes are able to maintain the balance in favor of the functioning of the molecules. The decrease in repair and replacement capacity is exacerbated by the fact that the enormously complex biomolecules that make up repair and replacement systems suffer the same fate as the biomolecules of their substrates. When the increasing loss of molecular fidelity eventually outweighs the ability to repair and replace, vulnerability to age-associated pathologies or diseases increases. In developed countries, the weakest links are the cells that make up the vascular system and those in which cancer is most likely to happen. The molecular instability that occurs in these cells is the weakest link that increases vulnerability to these two main causes of death (Hayflick, 2000, 2007b).

To understand how fundamental age changes occur might lead to a better knowledge of the etiology of all major causes of death (see Chapter 3).

1.4: Causality and chance in aging and longevity

The relationship between causality and chance is an open discussion in many disciplines. Often, the boundary among these events is thin to understand whether an occurrence is related to one or both. In particular, aging, the related diseases, and longevity are difficult to define as a consequence of causality, chance, or both (Accardi and Caruso, 2017).

Stochastic processes are accidental phenomena due to casual factors that play a key role in physiological and pathological events at the same level as genetics, epigenetics, and the environment. Indeed, stochastic processes contribute to the individuality of every living organism, including humans, influencing phenotypic variability, as suggested by the role of chance in the creation of the immunological repertoire and neuronal synapses (Accardi and Caruso, 2017). Living organisms are subject to nature laws and genetic programs where both Brownian random motion, i.e., the erratic random movement of particles in a fluid, as a result of continuous bombardment from molecules of the surrounding water molecules in the fluid, and crossing over contribute to leave space for the chance. Chance is just that, the random occurrence, i.e., an event happening not according to a plan (Accardi and Caruso, 2017).

There is evidence of the inherent stochastic nature of both gene expression and macromolecular biosynthesis. Several genes are in fact transcribed in minimal amounts of mRNA, which can cause large fluctuations in macromolecular biosynthesis. Genomic instability, which results in somatic mutations and chromosomal abnormalities, is another important source of intrinsic variability, as shown in aged mice, which have a mutation frequency up to 10− 4 per gene per cell. Reciprocally, the relatively low level of chromosomal aberrations observed in older persons should be a consequence of their genomic stability, hence a contributing factor to their attainment of advanced age (Kirkwood et al., 2005; Kirkwood, 2008; Vijg and Suh, 2013).

Genetic control ensures and guarantees the functionality of metabolic and development systems with a considerable degree of reliability and reproducibility. Nonetheless, there are small variations that can add up and cause large effects, for example, the significant variations in the size of some organs observed between genetically identical organisms. Underlying the visible phenotypic variations, there is a variety of sources of intrinsic variability within organisms observable at the molecular, cellular, and organ, and system levels, due to stochastic and epigenetic processes. All this can contribute to the differences observed in life span even in identical animals. In fact, the role of stochastic processes in aging has been demonstrated by studies conducted on inbred mice, which, as is well known, have the same genome. Well, despite the housing conditions are the same, the animals show a different life span, even up to 50% more. This demonstrates that there is a stochastic component that results in very few fluctuations in the genetic, epigenetic, environmental, and interaction components. This involves continuous microvariations which, accumulating over time, amplify the differences between individuals, manifesting themselves clearly in older ages (Kirkwood et al., 2005).

Epigenetics is used to describe phenotypic variations that may occur in cells following a different expression of individual genes without altering the DNA sequence. These phenotypic changes are stable and inheritable from cell progeny, through DNA replication and cell division cycles. Thus, during the proliferation that occurs in the normal homeostatic replacement, a cell expresses the characteristic genes of the corresponding tissue and not that characteristic of another one. In a broader sense, epigenetic processes are called to explain the changes in the regulation of the transcription of individual genes. Considering this broader definition of epigenetics, it is not surprising that the profound changes that occur with age in cells and tissues are also due to epigenetic processes as well as accumulation of nuclear and mitochondrial DNA mutations (Peaston and Whitelaw, 2006).

To fully understand the mechanisms underlying epigenetic modifications is important to elucidate how environmental and genetic factors cooperate to determine the aging process and aging-related phenotypes and diseases. On the contrary, data are accumulating which show that epigenetic modifications may represent important tools to monitor the rate and the quality of aging, or to warn for the onset of age-related diseases (Bellizzi et al., 2019). The level of complexity is very high if we consider that not only the effect of each variation but also their combinations must be evaluated. For example, lysine methylation at positions 4 and 9 in H3 has opposite effects, i.e., the first increases the expression of genes and the second reduces this action. miRNAs are also involved in gene transcription. They also regulate histone modification processes. Recent studies have, then, revealed that human aging can be characterized by a profile of circulating microRNAs that is predictive of chronological age and that can be used as a biomarker of risk for age-related outcomes (Bannister and Kouzarides, 2011; Cammarata et al., 2019; Dellago et al., 2017).

A recent study has presented the first long-term, longitudinal characterization of expression and splicing changes as a function of age and genetics (Balliu et al., 2019). The findings indicate that although gene expression and alternative splicing and their genetic regulation are mostly stable late in life, a small subset of genes is dynamic and is characterized by changes in expression and splicing and a reduction in genetic regulation, most likely due to an increase of environmental variance.

1.5: Conclusions and future perspectives

The aging process is driven by a lifelong accumulation of molecular damage, resulting in a gradual increase in the fraction of cells carrying defects. After sufficient time has passed, the increasing levels of these defects interfere with the performance of tissues and organs, resulting in a breakdown of self-organizing system and a reduced ability to adapt to the environment.

In fact, species are not selected for aging, but to survive until the age of reproduction and any parental care; the only way to live long is paradoxically to grow old. The animal machine has been selected to ensure efficient reproduction and possibly the protection of offspring, at the expense of possible deterioration in the following years. Throughout a series of mechanisms, partly endogenous and partly exogenous, multiple cellular alterations occur throughout life. These alterations would lead very quickly to aging and death if our organism did not possess important repair mechanisms, the efficiency of which is largely under genetic control. From the balance between aggressive factors, mainly conditioned by the environment, and factors that try to neutralize them, mainly conditioned by genetics, a different life span derives. For this reason, the way we age is not unambiguous and is not predictable. Over time, these factors condition a progressive loss of molecular precision with an accumulation of damage in cells, tissues, and the whole organism, in different ways in different individuals, so determining various phenotypes. Accordingly, the analysis of the age and function curves of the different individuals demonstrate that people, getting older, show increasingly differentiated levels of performance determining successful or unsuccessful aging. Hence, aging and longevity are related to the ability to cope with a variety of stressors (Caruso, 2019).

Contributing factors are cultural, anthropological, socioeconomic, sexual, and gender, ethnic differences, health care, epigenetics, and life occupation. In the case of nutrition, for example, a proinflammatory diet, containing an excess of refined sugars, animal proteins and saturated fats, and poor in nutraceuticals, directly contributes to increasing cell damage, while a Mediterranean-type diet, poor in refined sugars, animal proteins and saturated fats, as well as rich in nutraceuticals, decreases cell damage (Accardi et al., 2019; Aiello et al., 2019a, 2020).

Therefore, the ability to survive is the result of maintaining a suitable response to stressors within a well-established range, compatible with physical well-being. This could be an expression of a Gaussian (normal) distribution, in which centenarians represent its extreme tail. The centenarians would represent; therefore, the best adapted individuals, because they are equipped on a genetic or even stochastic basis, with more efficient maintenance and repair systems, to the different environmental conditions present during their life, and consequently capable of maintaining a suitable response to stressors, including microorganisms (Caruso, 2019).

As discussed in the second chapter, life expectancy has increased significantly, but the maximum life span of humans has not changed (about 120 years). Eliminating cancer or Alzheimer's disease would improve the quality of life, but it would not make us immortal, nor would it allow us to live much longer. To prolong life, it is necessary to intervene directly in the aging process. Further studies are therefore needed on the specific molecular changes of aging in search of key molecular components whose destruction leads, in cascade, to other damages. If such key components exist, then we will have targets for targeted interventions. It must be clear, however, that such interventions can postpone but not evade the inevitable molecular deterioration linked to the laws of physics.

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Chapter 2: Demographic aspects of aging

Annalisa Busetta; Filippa Bono    Department of Economics, Business and Statistics, University of Palermo, Palermo, Italy

Abstract

Population aging is occurring in almost all developed countries, albeit with differences in timing and intensity. This unprecedented phenomenon is evident not only in the change in the population age structure, but also in the impressive increase in the average length of life. After describing past, current, and future population trends, this contribution presents theories explaining the reasons for this long-term process that is completely reshaping the age structure of the population. It also describes the inequalities in aging (focusing in particular on the differences by gender, education, and cause of death) and introduces some measures of the individual health and economic consequences of population aging. The conclusions mention the main consequences of an aging society (e.g., problems related to the costs of health and pension programs for old people) and of an increase in individual life span (e.g., the effects on the well-being and lifestyles of individuals and on the social and economic lives of older people and their families).

Keywords

Population aging; Population structure; Life expectancy; Gender differences; Economic inequalities; Epidemiological transition

2.1: Introduction

Population aging is, together with population growth, urbanization, and international migration, one of the four megatrends of modern societies. This phenomenon, which is unprecedented in human history, is occurring in almost all developed countries, albeit with differences in timing and intensity. Every country in the world is experiencing growth in both the number and the proportion of older people in the population. Traditionally, measures of population aging are based on people's chronological age. In particular, the United Nations’ measures define old people as those aged 60 and over or those aged 65 and over. According to the UN 2019 Revision of the World Population Prospects (United Nations, 2020b), there are 728 million people aged 65 years and over in the global population in 2020 (Table 2.1), and this number will rise to more than 1810 billion by 2060 (compared to 262 million in