The Biology of Human Longevity

Inflammation, Nutrition, and Aging in the Evolution of Lifespans

Caleb E. Finch

• Publisher: Academic Press
• Year: 2010
• Print ISBN: 9780123736574
• eBook ISBN: 9780080545943
• Topic: Medicine
• Subtopic: Geriatrics

Written by Caleb Finch, one of the leading scientists of our time, The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans synthesizes several decades of top research on the topic of human aging and longevity particularly on the recent theories of inflammation and its effects on human health. The book expands a number of existing major theories, including the Barker theory of fetal origins of adult disease to consider the role of inflammation and Harmon's free radical theory of aging to include inflammatory damage. Future increases in lifespan are challenged by the obesity epidemic and spreading global infections which may reverse the gains made in lowering inflammatory exposure. This timely and topical book will be of interest to anyone studying aging from any scientific angle. - Author Caleb Finch is a highly influential and respected scientist, ranked in the top half of the 1% most cited scientists - Provides a novel synthesis of existing ideas about the biology of longevity and aging - Incorporates important research findings from several disciplines, including Gerontology, Genomics, Neuroscience, Immunology, Nutrition

CHAPTER 1

Inflammation and Oxidation in Aging and Chronic Diseases

Publisher Summary

This chapter provides an overview of experimental models for human aging and age-related diseases. In most chronic diseases of aging, oxidative stress and inflammation are prominent. Moreover, many tissues without specific pathology that show modest inflammatory changes during aging share major subsets of those in chronic diseases of aging. An overview of inflammation and oxidant stress in host defense suggests a classification of bystander damage. Mechanisms of inflammation are outlined, including the energy costs. This chapter also reviews in more detail inflammation in arterial and Alzheimer disease. These details are critical to understanding human aging and the role of insulin-like metabolic pathways. Many inflammatory processes emerge during “normal” or usual aging, but in the absence of specific diseases. The slow creep of inflammation from early years may drive the accelerating incidence of chronic diseases.

PART I

1.1. Overview

1.2. Experimental Models for Aging

1.2.1. Mortality Rate Accelerations

1.2.2. Mammals

1.2.3. Cultured Cell Models and Replicative Senescence

1.2.4. Invertebrate Models

1.2.5. Yeast

1.2.6. The Biochemistry of Aging

1.2.7. Biomarkers of Aging and Mortality Risk Markers

1.2.8. Evolutionary Theories of Aging

1.3. Outline of Inflammation

1.3.1. Innate Defense Mechanisms

1.3.2. Genetic Variations of Inflammatory Responses

1.3.3. Inflammation and Energy

1.3.4. Amyloids and Inflammation

1.4. Bystander Damage and Dependent Variables in Senescence

1.4.1. Free Radical Bystander Damage (Type 1)

1.4.2. Glyco-oxidation (Type 2)

1.4.3. Chronic Proliferation (Type 3)

1.4.4. Mechanical Bystander Effects (Type 4)

PART II

1.5. Arterial Aging and Atherosclerosis

1.5.1. Overview and Ontogeny

1.5.2. Hazards of Hypertension

1.5.3. Mechanisms

1.5.3.1. Inflammation

1.5.3.2. Hemodynamics

1.5.3.3. Aging

1.5.3.4. Endothelial Progenitor Cells

1.5.4. Blood Risk Factors for Vascular Disease and Overlap with Acute Phase Responses

1.6. Alzheimer Disease and Vascular-related Dementias

1.6.1. Neuropathology of Alzheimer Disease

1.6.2. Inflammation in Alzheimer Disease

1.6.3. Prodromal Stages of Alzheimer Disease

1.6.4. Overlap of Alzheimer and Cerebrovascular Changes

1.6.5. Insulin and IGF-1 in Vascular Disease and Alzheimer Disease

1.6.6. Blood Inflammatory Proteins: Markers for Disease or Aging, or Both?

1.7. Inflammation in Obesity

1.8. Processes of Normal Aging in the Absence of Specific Diseases

1.8.1. Brain

1.8.2. Generalized Inflammatory Changes in Normal Tissue Aging

1.9. Summary

PART I

1.1 OVERVIEW

Human life spans may have evolved in two stages (Fig.1.1A). In the distant past, the life expectancy doubled from the 20 years of the great ape-human ancestor during the evolution of Homo sapiens to about 40 years. Then, since the 18^th century, life expectancy has doubled again to 80 years in health-rich modern populations, with major increases in the post-reproductive ages (Fig. 1.1B) and decreases in early mortality (Fig. 1.1C). During these huge demographic shifts, human ancestors made two other major transitions. The diet changed from the plant-based diets of great apes to the high-level meat-eating and omnivory that characterizes humans. Moreover, exposure to infections increased. The great apes abandon their night nests each day and rarely congregate closely for very long in large groups. As group density and sedentism increased in our ancestors, so would their burden of infections and inflammation have increased from exposure to pathogens in raw animal tissues and from human excreta.

FIGURE 1.1 Evolution of the human life span. A. Life expectancy from 6 million years ago (MYA) to present. Left panel is simplified from Fig. 6.1. The shared ancestor of chimpanzee and human is predicted to have had a life expectancy at birth (qo) of 10 to 20 y, approximating that of wild chimps (Section 6.2.1). The range of q₀ from 30 to 40 y in early, but anatomically modern H. sapiens is hypothesized here to approximate that of current human foragers (Gurven and Kaplan, 2007) (Section 6.2.1; Fig. 6.1, legend) and pre-industrial Europe, e.g., England (Right panel). Life expectancy may have increased during the increase of brain size after 1.8 MYA (see Fig. 6.1 legend). Early Homo as a species was established by 1.8 MYA (Section 6.2) (Right panel). The major increase of life span speculatively began during later stages in evolution of H. sapiens, 0.5 to 0.195 MYA (see Fig. 6.1 legend and Section 6.2.2). Suppl. Fig. 5 and framed by historical markers of my interpretation. Data for England 1571–1847 from op. cit.; mean 36.2 y [30.6–41.7 y, 95% CI] calculated from Paine and Boldsen (2006), p.352 and (Wrigley and Schofeld, 1997). Global average life expectancy at birth in 2006: 64.8 y (weighted average, The World Factbook (CIA, 2006). B. Survival curves for Sweden showing the progressive increase in life span and rectangularization of the survival curves from 1751 to present. From Human Mortality Database. C. Mortality rate curves and aging (semi-log scale) for Sweden 1751, 1870, 1990, showing the historical trends for progressive downward shift of the entire mortality curve (See Fig. 2.7). Right panel, adapted from Oeppen and Vaupel (2002),

I propose that the growth of meat-eating and sedentism selected for gene variants adaptive in host defense and adaptive for high fat intake. Some of these genes may have favored the increased survival to later ages that enables the uniquely human multi-generational caregiving and mentoring. Many such genetic changes had probably evolved by the time of the Venus of Willendorf (cover photograph), 21,000 years ago in the Upper Paleolithic. Her manifest obesity may be viewed as adaptive in times of fluctuating food, with few ill consequences during the short lifespans of the pre-modern era, at the least, fewer than in the modern era of rampant chronic obesity. However, the most recent and rapid increases in life span cannot be due to the natural selection of genes for greater longevity.

I emphasize the plural lifespans, because many concurrent human life history schedules can be recognized in the world today that differ by the rate of growth, age of puberty and sexual maturation, the schedule of reproduction, and life expectancy. Evolutionary biologists recognize the huge plasticity of life history schedules, which vary between populations and respond rapidly to natural or artificial selection (Section 1.2.8). In the not too distant past, human life histories and lifespans may have been outcomes of natural selection, whereas changes in the last 2...

Table of contents

• Cover image
• Title page
• Table of Contents
• PREFACE
• ACKNOWLEDGMENTS
• Chapter 1: Inflammation and Oxidation in Aging and Chronic Diseases
• Chapter 2: Infections, Inflammogens, and Drugs
• Chapter 3: Energy Balance, Inflammation, and Aging
• Chapter 4: Nutrition and Infection in the Developmental Influences on Aging
• Chapter 5: Genetics
• Chapter 6: The Human Life Span: Present, Past, and Future
• BIBLIOGRAPHY
• NAME INDEX
• SUBJECT INDEX