The Role of Global Air Pollution in Aging and Disease: Reading Smoke Signals

By Caleb E. Finch

Global Air Pollution in Aging: Reading Smoke Signals is a complete reference connecting environmental pollution research to the human aging process. Since 1800, lifespans have more than doubled as infections declined and medicine improved. But the 20th century introduced a new global scourge of air pollution from fossil fuels with the potential to damage arteries, hearts and lungs that has been related to chronic exposure of air pollution from fossil fuels. Risk areas of study include childhood obesity, brain damage associated with air pollution, increased risk for autism in children and dementia in older adults.

In humans and animals, air pollution stimulates chronic inflammation in different organs, and genetic vulnerability to air pollution is being recognized, particularly for carriers of the Alzheimer risk gene ApoE4.

• Connects environmental pollution research to the human aging process
• Raises new issues relevant to the controversies on air pollution and global warming, challenging assumptions that lifespan will continue to increase in the 21st Century
• Examines the burden of air pollution to disadvantaged populations, with anticipated greater impact in developing countries which rely on fossil fuels for economic development in future decades

• Language: English
• Publisher: Academic Press
• Release date: Jan 21, 2018
• ISBN: 9780128131039

Caleb E. Finch

Dr. Finch’s major research interest is the study of basic mechanisms in human aging with a focus on inflammation. He has received numerous awards in biomedical gerontology, including the Robert W. Kleemeier Award of the Gerontological Society of America in 1985, the Sandoz Premier Prize by the International Geriatric Association in 1995, and the Irving Wright Award of AFAR and the Research Award of AGE in 1999. He was the founder of the NIA-funded Alzheimer Disease Research Center in 1984 and currently serves as co- Director. Dr. Finch became a University Distinguished Professor in 1989, an honor held by sixteen other professors at USC who contribute to multiple fields. He is a member of five editorial boards and has written four books including The Biology of Human Longevity (Academic Press 2007) as well as over 470 articles.

Book preview

The Role of Global Air Pollution in Aging and Disease

Reading Smoke Signals

Caleb E. Finch

Table of Contents

Cover image

Title page

Copyright

Dedication

Preface

Acknowledgments

Chapter 1. The Three Smokes in Global Mortality

1.1. Overview

1.2. Airborne Toxins, a Primer

1.3. Caveats From Cigarettes

1.4. The Three Smokes and Mortality

1.5. Interactions of the Three Smokes

1.6. The History of Air Pollution During Expanding Longevity

1.7. Conclusions

Chapter 2. The Toxic Nature of the Three Smokes

2.1. Overview

2.2. Particle Size and Chemistry

2.3. Source Apportionment in Morbidity and Mortality

2.4. Cigarette Smoke

2.5. Household Air Pollution, Biomass Smoke, and Dust

2.6. Mechanisms

2.7. The Dark Passage: Does Inhaled Particulate Matter Reach the Brains of Adults and Embryos?

2.8. Conclusions

Chapter 3. Air Pollution in Diseases of Aging

3.1. Overview

3.2. Arterial Thickening and Atheroma Formation

3.3. The Brain

3.4. Interactions of Ambient Air Pollution and Cigarette Smoke

3.5. Conclusions

Chapter 4. Air Pollution and Cigarettes Cloud Development

4.1. Overview

4.2. Prematurity, Birthweight, and Placentation

4.3. Body Weight and Obesity

4.4. Brain Development

4.5. Mechanisms

4.6. Epigenetics

4.7. Conclusions

Chapter 5. Air Pollution in Our Future Longevity

5.1. Overview

5.2. Trends in Air Pollution

5.3. Health Benefits From Reducing Exposure to Air Pollutants

5.4. Trends in Longevity: Does Our Evolutionary Past Predict the Future?

5.5. When the Future Exposome Meets the Genome of the Past

5.6. Reading Smoke Signals: A Synopsis

5.7. Conclusion

Glossary

Subject Index

Copyright

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Dedication

To Doris Jane Finch, my best friend, wife and closest colleague, who has nurtured my mind and spirit during the writing of this book and its four antecedents.

Preface

Writing this monograph on air pollution and aging has taken me to new venues in my lifelong exploration of the biology of longevity (Finch, 1990). One root of this journey began two decades ago in reviewing the genetics of longevity (Finch and Tanzi, 1997; Finch and Ruvkun, 2001). The evidence forced us to the unexpected and unwelcomed (!) conclusion that the heritability of life span accounts for less than 35% of individual variations of identical twins, but also of lab mice, flies, and worms. Simply put, if you are born with human genes, you may live to 50 or 90   years, but you will always outlive a mouse, 30 times over. Because the life spans of inbred worms hatching in the same dish vary as much human twin life spans, we also recognize stochastic molecular events in individual outcomes of aging (Finch and Kirkwood, 2000 ). The larger conclusion remains that the environment and lifestyle are stronger determinants of individual aging than most genetic variations.

Another root was my experimental research, which showed that genes for inflammation had increased activity in Alzheimer disease and in normal brain aging of men and mice (May et al., 1990; Johnson et al., 1992). I also developed collaborations with anthropologists Hilly Kaplan and Mike Gurven and demographer Eileen Crimmins to explore patterns of aging in environments with high inflammation and short life spans (Finch and Crimmins, 2004; Gurven et al., 2008; Finch, 2007).

An earlier root of my thinking stems back to the 1960s as a predoc at Rockefeller University, where I had seminal discussions on gene expression during development with the great Alfred Mirsky and his recent predocs Eric Davidson and Bruce McEwen (McEwen et al., 1992; Finch, 2016). Not only does differential gene expression lead to organogenesis, but our adult health is shaped by environmental influences that modify gene expression such as maternal malnutrition and stress. Using that premise, my PhD research analyzed age changes in gene expression during cold stress (Finch et al., 1969; Finch, 1972).

Fast forward to University of Southern California (USC). My lab’s expertise in brain aging and Alzheimer disease gave a basis for a multilab study on air pollution. Discussions with epidemiologists Brian Henderson, Malcolm Pike, and John Peters led me to air pollution as a factor in aging by their findings that air pollution increased the risk of lung cancer (Henderson et al., 1985) and accelerated atherosclerosis (Künzli et al., 2005). In 2009, USC funded our pilot study of air pollution effects on mouse brain inflammation. This new direction was enabled by collaboration with Costas Sioutas of Civil Engineering, who developed technology for collection of urban air particles and exposure of mice under controlled conditions. Initial studies showed that nanoscale particles cause selective changes in glutamate receptors in memory circuits (Morgan et al., 2011). Most recently, we collaborated with epidemiologist J-C Chen to show that air pollution particles accelerate brain amyloid production in mice and that older women residing in high pollution have nearly doubled risk of dementia (Cacciottolo et al., 2017). Moreover, the Alzheimer risk gene ApoE4 increased vulnerability to air pollution, adding bullets to the smoking gun (Dekosky and Gandy, 2014).

Writing this book has led me into literatures that often have little cross-talk. A short list includes biogerontology, neurobiology, and geriatrics; demography and epidemiology; toxicology of air pollution and tobacco; climate change; and policy of energy and urban planning. Delving into these diverse literatures, I found numerous studies involving the main sources of inhaled pollution: cigarettes, biomass burning in household smoke, and ambient air pollution caused by hydrocarbon emission from industry and traffic—the three smokes. Most studies considered only one airborne pollutant by methods that often differed by subdiscipline.

Cigarette smoking shows gene–environment interactions that cause many of the same outcomes as air pollution, from lung cancer to dementia. Moreover, smoke from biomass burning shares some chemical characteristics with fossil fuels and tobacco. Airborne toxins from the three smokes may synergize at multiple levels, but their convergence has not been well integrated into mainstream thinking of health and aging. Because inflammation mediates many aging processes, I suggest that air pollutants be broadly considered as gerogens.

The low heritability of life span also points to a new horizon of environmental gerontology. To understand the diversity of outcomes in aging, we must consider the full range of environmental influences on later-life health. "Environmental gerontology initially considered how the well-being of elderly depended on their sociophysical environment," particularly housing and institutionalization (Scheidt and Schwartz, 2010; Scheidt and Norris-Baker, 2012). The scope of environmental gerontology should be expanded across the life span to include airborne pollutants and their interactions with diet and exercise, as well as housing. More broadly, environmental gerontology is seated within the exposome, a robust framework for analyzing the totality of external and internal environmental factors of individual health ( Section 1.2 ; Vineis et al., 2017). Chapters 4 and 5 discuss the potential for multigenerational impact of environmental exposure on aging by epigenomic mechanisms.

My main conclusions from this inquiry are (1) that airborne pollutants from diverse sources share many physical–chemical activities; (2) that individual aging patterns are the outcome of gene–environment interactions in inflammatory processes that are at the core of aging and of high importance; (3) that existing technology could be used to rapidly diminish global pollution with major benefit to global health and life span. I have tried to make the text accessible for the general readership concerned with global climate and pollution, as well as for academic specialists. This agenda cannot be achieved in isolation because murky air knows no borders. What befouls the atmosphere in one part of the globe affects the health and economy of the rest of it.

References

Cacciottolo M, Wang X, Driscoll I, Woodward N, Saffari A, Reyes J, Serre M.L, Vizuete W, Sioutas C, Morgan T.E, Gatz M, Chui H.C, Shumaker S.A, Resnick S.M, Espeland M.A, Finch C.E, Chen J.C.Particulate air pollutants, APOE alleles, and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models.  Transl. Psychiatry . 2017;7:e1022.

Dekosky S.T, Gandy S. Environmental exposures and the risk for Alzheimer disease: can we identify the smoking guns?  JAMA Neurol.  2014;71:273–275.

Finch C.E, Foster J.R, Mirsky A.E. Aging and the regulation of cell activities during exposure to cold.  J. Gen. Physiol.  1969;54:690–712.

Finch C.E. Enzyme activities, gene function and ageing in mammals.  Exp. Gerontol.  1972;7:53–67.

Finch C.E.  Longevity, Senescence, and the Genome . U Chicago Press; 1990.

Finch C.E, Tanzi R.E. The genetics of aging.  Science . 1997;278:407–411.

Finch C.E, Kirkwood T.B.L.  Chance, Development, and Aging . Oxford U Press; 2000.

Finch C.E, Ruvkun G. Genetics of aging.  Annu. Rev. Genom. Hum. Genet.  2001;2:435–462.

Finch C.E, Crimmins E.M. Inflammatory exposure and historical changes in human life spans.  Science . 2004;305:1736–1739.

Finch C.E.  The Biology of Human Longevity: Nutrition, Inflammation, and Aging in the Evolution of Lifespans . San Diego: Academic Press; 2007.

Finch C.E. Eric Davidson’s early years in development.  Dev. Biol.  2016;412(2 Suppl.):S3–S4.

Gurven M, Kaplan H, Winking J, Finch C.E, Crimmins E.M. Aging and inflammation in two epidemiological worlds.  J. Gerontol. Med. Sci.  2008;63A:196–199.

Henderson B.E, Gordon R.J, Menck H, Soohoo J, Martin S.P, Pike M.C. Lung cancer and air pollution in south central Los Angeles County.  Am. J. Epidemiol.  1985;101:477–488.

Johnson S.A, Lampert-Etchells M, Rozovsky I, Pasinetti G, Finch C. Complement mRNA in the mammalian brain: responses to Alzheimer’s disease and experimental lesions.  Neurobiol. Aging . 1992;13:641–648.

Künzli N, Jerrett M, Mack W.J, Beckerman B, LaBree L, Gilliland F, Thomas D, Peters J, Hodis H.N.Ambient air pollution and atherosclerosis in Los Angeles.  Environ. Health Perspect.  2005;113:201–206.

May P.C, Lampert-Etchells M, Johnson S.A, Poirier J, Masters J.N, Finch C.E.Dynamics of gene expression for a hippocampal glycoprotein elevated in Alzheimer’s disease and in response to experimental lesions in rat.  Neuron . 1990;5:831–839.

McEwen B.S, Finch C. Alfred E. Mirsky and the foundations of molecular biology and neuroendocrinology.  Endocrinology . 1992;130:6–7.

Morgan T.E, Davis D.D, Iwata N, Tanner J.M, Snyder D, Ning Z, Kam W, Hsu Y.T, Winkler J.W, Chen J.C, Petasis N.A, Baudry M, Sioutas C, Finch C.E.Glutamatergic neurons in rodent models respond to nanoscale particulate urban air pollutants in vivo and in vitro.  Env. Health Perspect.  2011;119:1003–1009.

Scheidt R, Schwarz B. Environmental gerontology: a sampler of issues and applications. In: Cavanaugh J, Cavanaugh C, eds.  Aging in America: Psychological Aspects . vol. 1. Santa Barbara, CA: Praeger; 2010:156–176.

Scheidt R.J, Norris-Baker C. Understudied older populations and settings in environmental gerontology: candidates for future research.  J. Hous. Elder.  2012;26:251–274.

Vineis P, Chadeau-Hyam M, Gmuender H, Gulliver J, Herceg Z, Kleinjans J, Kogevinas M, Kyrtopoulos S, Nieuwenhuijsen M, Phillips D.H, Probst-Hensch N, Scalbert A, Vermeulen R, Wild C.P.EXPOsOMICS Consortium. The exposome in practice: design of the EXPOsOMICS project.  Int. J. Hyg. Environ. Health . 2017;220(2 Pt A):142–151.

Acknowledgments

Professors Todd Morgan, Henry Forman (Gerontology) and Costas Sioutas (Civil Engineering) were my essential coinvestigators in experimental studies of Chapters 2–4. Todd is a superb mentor to our undergrads, predocs, postdocs, and technicians who generated these novel data. We thank the Cure Alzheimer Fund and the NIA for supporting these projects.

Readers gave thoughtful and critical comments and saved me from several howlers: Jennifer Ailshire (Chapters 1, 4, and 5), George Ban-Weiss (Chapters 2 and 5), Mafalda Cacciottolo (Chapter 3), Eileen Crimmins (Chapters 1 and 5), Marja Jylhä (Chapters 3–5), Todd Morgan (Chapters 1–3), Arian Saffari (Chapters 1 and 2), Costas Sioutas (Chapters 1–3), Ben Trumble (Chapter 5), and Jim Zhang (Chapters 1–3). Graphs were drawn by Troy Palmer with skill and care. Emily Nabors edited the text with insight and exactitude.

I appreciate the diligence of Stacy Masucci, Acquisition Editor; Mohana Natarajan, Production Manager; Vicky Pearson, Designer; and Sam Young, Project Manager.

Lastly and firstly, I thank the University of Southern California Presidents, Provosts, and Deans for freedom to develop this and other projects that were far from mainstream. These pages were written during the stewardship of Dean Pinchas Cohen, Vice President Randolph Hall, Provost Michael Quick, and President C.L. Max Nikias.

Chapter 1

The Three Smokes in Global Mortality

Abstract

Airborne toxins cause 14   million premature deaths worldwide according to the World Health Organization. Most of these toxins arise from fossil fuels, cigarettes, and inefficient home fires that I designate as "the three smokes." Their microscopic particles share toxic properties that exacerbate oxidative stress and inflammation and accelerate many aging processes. Dust from the earth's crust can also be toxic. Air pollution particles are characterized by size, with standards set for particles smaller than 2.5   μm (PM2.5). The particles and gases that comprise air pollution are also included in the exposome, a global environmental assemblage of toxin exposure, starting at conception and extending across the life span. Some individuals or groups may be resistant to airborne toxins, as shown for elderly surviving cigarette smokers. The growing exposure to toxins from fossil fuels and tobacco since 1800 was concurrent with longevity increases. In essence, we have swapped mortality caused by infections for accelerated aging from fossil fuels and cigarettes. The toxic mechanisms in airborne particles are considered in the next chapters.

Keywords

Ambient air pollution; Biomass burning; Cigarette smoke; Dust; Exposome fossil fuels; Household air pollution; Longevity; Mortality rates; PM10; PM2.5; Toxicity

Chapter Outline

1.1 Overview

1.2 Airborne Toxins, a Primer

1.3 Caveats From Cigarettes

1.4 The Three Smokes and Mortality

1.4.1 Ambient Air Pollution

1.4.2 Cigarettes

1.4.3 Biomass Smoke, Inside and Out

1.4.4 Plus Dust

1.5 Interactions of the Three Smokes

1.6 The History of Air Pollution During Expanding Longevity

1.7 Conclusions

References

1.1. Overview

Environmental gerontology is upon us: Because of the low heritability of life span (Preface), we must look to lifestyle and environment as the strongest determinants of the life span. Not only do individual outcomes of aging depend on lifestyle choices of diet and exercise, but also individuals have different exposure to ubiquitous airborne toxins that have major roles in aging.

The World Health Organization (WHO) now recognizes that air pollution promotes many diseases of aging and kills prematurely. Globally, 15   million adults per year die from noncommunicable diseases attributable to airborne toxins (Table 1.1), mainly heart attacks and strokes, cancer, and chronic obstructive pulmonary disease (COPD). Moreover, airborne toxins from fossil fuels and cigarettes are linked to metabolic dysregulation and dementia (Chapter 3, Table 3.1). Even worse, air pollution impacts our pre- and postnatal development with manifold consequences throughout life (Chapter 4). Exposure during development impacts brain myelination and also increases obesity, a risk factor in heart disease and dementia. The smoke from fossil fuels joins that from cigarettes, causing most of the premature, or avoidable, mortality.

Table 1.1

Mortality from noncommunicable disease is 38   million/year. Also see Lelieveld et al. (2015) and Landrigan et al. (2017).

In addition, nearly 3   billion breathe also noxious household third-hand smoke from biomass fuels such as wood or dried dung (WHO Indoor Air Pollution, 2017). Thus, we must consider airborne toxins from the three smokes: biomass, fossil fuels, and cigarettes. I propose that the airborne toxins from ambient air pollution (AAP), cigarette smoke (CS), and household air pollution (HAP) be considered as gerogens, or agents that accelerate aging processes. Airborne toxins from fossil fuels and cigarettes induce oxidative stress and inflammatory responses shared with many aging processes.

My synthesis of this huge literature will emphasize findings from studies of large population samples and experimental studies with laboratory animals and cultured cells. Combustion of fossil fuels, biomass, and tobacco yields particles and vapors that penetrate deep into our lungs, with broader impact than that was initially understood for tobacco carcinogens. The three smokes cause oxidative stress and induce genes for detoxification and inflammatory pathways throughout the body (Chapter 2). These toxic effects of fossil fuels, biomass, and tobacco are convergent: as organic materials, their shared components are ultimately derived from the combustion and degradation of organic residues of animals, plants, and microbes. Their main initial impact is in the respiratory tract, followed by indirect responses throughout the body that even cross the placenta to alter brain development. Ultimately, we will understand their interactions with aging as outcomes of selective gene regulation with influences of genetic variants.

Your author is a human biologist with an active wet-lab program on the neurobiology of aging. Our focus reflects collaborations with demographers, epidemiologists, and field anthropologists. I am keenly aware that correlation does not prove causality. Individual variation and subgroup diversity within populations frustrate unequivocal conclusions about causality of airborne toxins. Identical twins who are concordant for Alzheimer disease can differ up to 16   years in dementia onset (Gatz et al., 2010). Even inbred mice and worms do not respond identically within any experiment. Individual differences despite identical genes are attributable to intrinsic noise at the subcellular level from Brownian motion stochastic variations (Finch and Kirkwood, 2000).

Gene–environment interactions are also emerging for air pollution. Recent studies from my lab show gene–environment interactions for ApoE4 and air pollution in Alzheimer neurodegeneration (Cacciottolo et al., 2017, Chapter 3.3.3). Several levels of gene–environment interactions are discussed, including epigenetic changes with multigenerational potential. Where possible, I document human population findings with molecular mechanisms.

The first two chapters give a foundation for more mechanistic discussions. Next ahead is a global profile of airborne toxins from the three smokes, in which I include the desert dust with which they commingle. The historically recent spread of airborne toxins from fossil fuels and cigarettes coincides with the globally increasing life spans and with the gradual elimination of infectious disease. Chapter 2 reviews the chemical and physical nature of airborne toxins and the efforts to identify which components are mostly linked to diseases. The multiple carcinogens in CS give a model for thinking about the even greater diversity of airborne toxins from vehicular traffic. We know surprisingly little of how inhaled toxins act on our organs and cross the placenta. Chapter 3 reviews diseases that are associated with adult exposure to the three smokes, anticipating developmental exposure in Chapter 4. Lastly, I ponder the future in Chapter 5. Some countries have made exemplary improvements of health from the reductions of air pollution and decreased smoking. However, these encouraging steps are shadowed by the predictions for global warming and increased ambient pollutants, to which I would add increased insectborne infections. Future human life spans are likely to become even more uneven across the world (Finch et al., 2014).

1.2. Airborne Toxins, a Primer

The main airborne toxins arise from the combustion of fossil fuels, tobacco, and biomass, which I call the three smokes (Table 1.1). Together, the three smokes were associated with 15   million excess (premature) deaths per year, which is about one-third of adult mortality from noncommunicable diseases. Outdoor, or AAP, currently receives the most attention by media and regulatory agencies. AAP is a mixture of aerosols from natural and industrial origins with carbonaceous particles, minerals and salts, gases, and volatile chemicals. Indoor, or HAP, includes invecting (ingressing) AAP plus CS plus smoke from household (domestic) burning of wood and dung for cooking and heating.

Globally, less than 5% of aerosol particles have human origins. The nonanthropogenic particulate material (PM) largely comes from marine aerosols and mineral dust (Table 1.2). Of the man-made PM10, fossil fuels account for only 0.03% of total global aerosols by mass (4   Tg of the total 12,000   Tg/year) (Viana et al., 2014). However, in urban environments, about 20% of the PM arises from vehicular traffic emissions (Table 2.1B, Chapter 2). While relatively small by mass, fossil fuel aerosols are associated with a disproportionate toxicity causing premature mortality equivalent to that caused by CS.

Table 1.2

PM, particulate material; the number represents its diameter in microns.

Adapted from Kreidenweis et al. (1999, Table 4.1) and Sternberg (2015, Table 8.2).

AAP from combustion of fuels was designated by the WHO as the largest single environmental health risk, worldwide, exceeding that from cigarettes (WHO, 2016). For global PM2.5 in 2014, only 8% of the world’s population resided within the WHO Air Quality Guideline of 10   μg/m³ (Table 1.3). By comparison, 92% of Western Europe and 76% of North America met the WHO guidelines (Brauer, 2010). At the opposite extreme, only 1% of residents in South and East Asia breathed air that meets the WHO standards. First identified with lung diseases, AAP was soon recognized for accelerating arterial disease and cancer risk, and most recently dementia (Chapter 3). Moreover, AAP synergizes with CS in lung cancer. Worse yet, the fetal development and postnatal development are impacted by indoor and outdoor air pollution and by secondhand CS (Chapter 4). There is no safe minimum exposure to man-made airborne toxins from fossil fuels of tobacco.

Table 1.3

ann av, annual average; y, year.

a  The PM size classes recognized by EPA are defined by size filters with 50% efficiency for retaining PM of each aerodynamic diameter in