The Quest for Human Longevity

Science, Business, and Public Policy

Lewis D. Solomon

• Publisher: Taylor & Francis
• Year: 2017
• eBook ISBN: 9781351475594
• Edition: 1
• Topic: Politics & International Relations
• Subtopic: Politics
• Index: Politics & International Relations

"Many scientists today are working to retard the aging process in humans so as to increase both life expectancy and the quality of life. Over the past decade impressive results have been achieved in targeting the mechanisms and pathways of aging. In The Quest for Human Longevity, Lewis D. Solomon considers these scientific studies by exploring the principal biomedical anti-aging techniques. The book also considers cutting edge research on mental enhancements and assesses the scientific doubts of skeptics. The Quest for Human Longevity is also about business. Solomon examines eight corporations pursuing various age-related interventions, profiling their scientific founders and top executives, and examining personnel, intellectual property, and financing for each firm. Academic scientists form the link between research and commerce. Solomon notes that the involvement of university scientists and researchers follows one of two models. The first is a traditional model in which scientists leave academia to work for a corporation or remain in academia and obtain business support for their research. The second is a modern model in which scientists use their intellectual property as a catalyst for acquiring equity interests in the firms they organize. Critics have pointed to the dangers of commercialized science, but Solomon's analysis, on balance, finds that the benefits outweigh the costs and that problems of secrecy and conflicts of interest can be addressed. If scientists succeed in unlocking the secrets of aging and developing drugs or therapies that will allow us to live decades longer, the consequences for society will include profound social, political, economic, and ethical questions. Solomon deals with the public policy aspects of significant life extension and looks at the conflict between those who advocate the acceptance of mortality and the partisans of life. The Quest for Human Longevity will be of interest to policymakers, sociologists, scientists, and studen"

1

The Second Longevity Revolution

The twenty-first century opens the possibility of a dramatic extension of human lifespan. It is an all too alluring quest. Yet, a yearning as old as civilization to extend the human lifespan may be within reach.

The quest for longevity, marked by a life free of disease and disability, has long been a dream of humans. The idea of living longer, of finding the “fountain of youth,” has attracted adventur-ers for centuries. Ponce de Leon, the Spanish explorer, is probably the best known. While serving as the governor of what is now Puerto Rico, legend has it that he heard tales from the local population about an island with a spring that restored youth to anyone who drank from it. Ponce de Leon mounted an expedition to find the island in 1513, nearly five hundred years ago. Although the island proved elusive, he discovered what is now Florida.

We may be at the cusp of the second longevity revolution. The first longevity revolution mainly occurred during the first half of the twentieth century. We made progress despite the toll from cigarette smoking that flourished during this period. Sanitation improved tremendously. Vaccines were developed. Infant and maternal mortality declined; infectious diseases were conquered and nutrition improved. During the second half of the last century, a significant reduction in deaths occurred related to the more successful treat-ment and prevention of heart disease and cancer.

Over the past one hundred years, medicine altered the life expectancy curve. An American woman born in 1900 could expect to live to roughly age fifty, a man slightly less. In the United States, a female born in 2004 can expect to live to slightly more than eighty, a man to about seventy-four.¹ Many more people enjoy the opportunity to become old and face age-related, life-threatening pathologies.

While medicine has made many advances, the elderly still encounter numerous problems that characterize the wasting away of the human body and brain. Physical and mental abilities of seniors decline and decay.² As we age, we lose our resiliency, the ability to bounce back when our body’s equilibrium is disrupted by viruses, bacteria, infection, or accidents. We become more susceptible to a variety of age-related illnesses, including heart disease, hypertension, Parkinson’s disease, Alzheimer’s disease, stroke, and cancer.

Aging is characterized by the deterioration of every tissue, organ, and system in the body. It occurs in a progressive manner, beginning, for most of us, in our late thirties and early forties. The consequences of aging are so pervasive and intertwined with degenerative diseases that it is difficult to measure the rate of aging. Many of the features of aging are characteristic of deadly diseases and conditions. Thus, often it is difficult to separate aging from the disease processes.

To facilitate the second longevity revolution, some scientists want to retard or stop our physical deterioration. They seek to intervene in the general process of aging, thereby increasing not only the average human life (one’s life expectancy) but also the maximum number of years humans can live (one’s lifespan). Importantly, researchers also seek to significantly increase the quality of life during the additional decades of existence, permitting individuals to remain active for virtually their entire lives, with death coming quickly, for instance, from a heart that cannot keep pumping, so that a compression of morbidity will accompany life extension. In addition to slowing aging and keeping the body free from disease, scientists also want to preserve mental sharpness as we grow old. They search for a magic pill or therapy to extend life and tackle many problems simultaneously. In so doing, these researchers assume that there is a general, body-wide process of aging.

For centuries, aging was understood as the scattered, rather chaotic, but the inevitable breakdown of the human body, its tissues and organs. Similar to a car with too many miles, the consensus was that the body eventually wears out. Even if you fix one part, others will give out. The human machine was thought to inexorably break-down.

Until recently, the process of aging was not thought to be amenable to intervention. As a result of the body’s interaction with the environment and a poor understanding of the workings of human genes, aging was considered too complex to solve. Although our biological clocks tick at different rates, it was seen as inevitably occurring. Thus, we were admonished to accept our finitude and make old age more manageable.

An intense, methodical quest is now under way to turn off aging and extend life using proven science. A hunt is underway to discover the repair mechanisms that work so well during youth. If we understand these natural repair systems, we should be able to reset them or use them to repair the body as it advances in years. According to Bruce N. Ames, a noted scientist, whose work is discussed in chapter 3, “Once scientists understand the mechanism [of aging], there are hundreds of ways to intervene.”³

Over the past decade, respected scientists achieved impressive results in their laboratories, which were then scrupulously checked and peer-reviewed. These legitimate researchers at top-flight academic institutions see aging as subject to slowing. Some even see the possibility of reversing any age-related decline that has already occurred and restoring vitality and function, thereby combating the aging process “to achieve a perpetually youthful physiological state.”⁴ In their search, these prolongevity scientists start with aging, targeting the mechanisms and pathways of aging, not any specific disease itself.

The Science

This work considers the ongoing scientific studies that are attempting to understand the mechanisms and pathways of aging and discover the means by which we might to postpone aging. Specifically, this book examines four anti-aging techniques:

1. Lengthening telomeres and/or actuating telomerase, thereby extending or stabilizing the strips of DNA that cap the ends of our chromosomes (chapter 2).

2. Natural or synthetic anti-oxidants to neutralize the free radicals our cells produce as they convert sugar to produce energy (chapter 3).

3. Caloric restriction mimics that will duplicate the benefits of trimming food intake (chapter 4).

4. Genetic manipulation, using modern molecular genetic tools to manipulate DNA, our basic genetical material, to rearrange or alter genes, thereby promoting age-retarding genes (chapter 5).

Scientific discoveries in the 1990s helped legitimize the field of aging genetics. By turning on or off certain genes, for example, researchers achieved success in doubling and tripling the lives of simple organisms, including yeast, fruit flies, and worms, and even more complex ones, such as mice. They even achieved an astounding sixfold increase for worms. These organisms not only put off death but also the hobbling conditions of old age. With these scientific results, one could hypothesize that human beings could live to 150 or 160 years (or even longer). Research may enable humans to slow down aging, increase the maximum lifespan, and enable people to remain vigorous longer, with a less decrepit and burdensome old age.

This book also considers cutting-edge research on mental enhancement (chapter 6). Living longer is less desirable if mental agility continues to deteriorate. It may be possible that at 150, humans could have the physical and mental agility of a seventy-five-year old, and not spend the extra seventy-five years babbling in a nursing home. We may live in a world where each of us does not outlive his or her brain.

Numerous naysayers exist when it comes to the idea of significant life extension. They often base their negativity on the Hayflick limit, named after Leonard Hayflick, Ph.D., a cell biologist. In the early 1960s, Hayflick, then a researcher at the Wistar Institute of Anatomy and Biology, found that normal human cells, when taken from the body and grown in a glass dish (more technically, in vitro) divide about fifty times, then stop replicating and lapse into senescence.⁵ Senescence connotes a natural process of cellular decay, a loss of biological vigor, that ultimately leads to a cell’s death.

Hayflick discovered what he characterized as the finite replicative capacity of normal human cells that serve as the building blocks for all human tissues. Cell division plays a key role in the normal growth, maintenance, and repair of tissues. According to the Hayflick limit, cellular division is, however, a limited process in the human body. Programmed by a biological clock, likely genetically controlled, cells are mortal. They do not and cannot live forever because over time they lose their ability to accurately copy the DNA — the genetic code—inside their nuclei and carry out housekeeping tasks, such as exporting wastes. The cellular aging process, which occurs in numerous tissues in the human body, causes, or at least contributes to, a variety of chronic degenerative diseases and conditions, including atherosclerosis, the narrowing of arteries that reduces blood flow to organs, and macular degeneration, a disease of the eyes that generally leads to vision loss.

Scientists broke through the Hayflick limit in 1998, as discussed in chapter 2, when human cells given a copy of the telomerase gene, an enzyme, proved able to divide many times beyond the fifty or so barrier. However, many scientists continue to believe there is a biological brick wall curtailing average human life expectancy, with an average upper limit of ninety years, assuming the elimination of diabetes, cardiovascular diseases, and cancer, with a more realistic average ceiling of eighty-five years.⁶

Despite the breaking of the Hayflick limit that “undermined the concept that death is inevitable because of some inherent weakness in the living cell,”⁷ Hayflick and other leading scientists cautioned against the dramatic claims made by life extension enthusiasts. Hayflick and fifty other internationally recognized scientists, including three featured in chapter 2 (Carol W. Greider, Jerry W. Shay, and Woodring E. Wright) and one discussed in chapter 5 (Thomas T. Perls), published a manifesto in which they concluded: “The prospect of humans living forever is as unlikely today as it has always been, and discussions of such an impossible scenario have no place in scientific discourse.”⁸ However, life extension even to 150 or 160 years is not the same as immortality.

Shortly after the issuance of the manifesto, Hayflick and two coauthors, including S. Jay Olshansky, Ph.D., a noted gerontological demographer, published an article in Scientific American.⁹ The trio asserted that “no currently marketed intervention—none—has yet been proved to slow, stop or reverse human aging and some can be downright dangerous.”¹⁰ Looking to the future, they continued, “The lack of a specific genetic program for aging and death means that there are no quick fixes that will permit us to treat aging as if it were a disease. A single genetic intervention in an organism as complex as a human being would have little chance of combating the probably vast array of genes and biological activities that play subtle, unpredictable parts in the timing of our ultimate demise.”¹¹

Research focusing on whether there is an anti-aging intervention that will slow, stop, or even reverse the aging process now occupies many brilliant minds. While the doubters’ negativity may be extreme, the results of numerous studies considered in this book are promising, although not yet conclusive, and the modern fountain of youth may prove a mirage. Aging may be so complex that it may not be slowed by a single drug or therapy. If aging is a collection of processes, multiple interventions may be needed—many pills, not one, taken day in and day out for years—to keep people young, robust, and mentally alert. As one life extension proponent put it, “Aging is multifaceted, so therapies that emerge will likely be an amalgam of behavioral, dietary, genetic, and pharmacological elements, with differing efficacies against various aspects of the process.”¹² Or, aging may be a unitary process governed by a relatively few genes. Tweaking a dozen or so genes in humans may be a solvable problem. Scientists may discover a single “magic bullet” that works for everything, at least physically.

Others maintain that we must use caution in extrapolating from experiments with fruit flies and worms, among other short-lived species, which are subject to hazardous environments, unlike humans. Their lifespan is constrained and flexibly regulated to coordinate their survival and reproduction in a way quite different that of humans. They are also far less complex and more genetically determined.¹³ Although the genes of worms and humans are remarkably similar, the genes in both do not always function identically.

In addition, any intervention that alters the workings of a powerful master gene, may, for example, stir up unintended effects, such as infertility, sluggish metabolism, or weakened immunity. Similar to all drugs available on today’s market, age-retarding drugs may have uneven effects: working for some, but not for others.¹⁴

Even if researchers overcome these obstacles, will the anti-aging intervention just enable people to spend extra decades with the infirmities of old age — expand morbidity — or will it prolong youthfulness and slowdown or postpone the onset of age-related diseases, such as cancer and Alzheimer’s? Will there by uncoordinated increases in vigor, physically stronger bodies but weaker memories?

Despite these doubts and questions, the quest for longevity continues apace on two fronts: first, basic research; and second, the commercialization of discoveries.

Biomedical Businesses

In addition to considering the science of life extension, this is a book about business. This work analyzes eight corporations pursuing age-related biomedical interventions as well as their founders and current top executives: Geron Cor...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Table of Contents
• 1. The Second Longevity Revolution
• 2. The Ups and Downs of Telomeres and Telomerase: Geron Corp.
• 3. Oxidative Damage from Free Radicals and the Anti-Oxidant Antidote: Juvenon, Inc. and Eukarion, Inc.
• 4. Caloric Restriction and Its Mimics: BioMarker Pharmaceuticals, Inc.
• 5. Genetic Manipulation, Its Mimics, and Biochemical Activators: Elixir Pharmaceuticals, Inc.
• 6. The Search for Memory-Enhancing Drugs: Helicon Therapeutics, Inc., Memory Pharmaceuticals Corp., and Cortex Pharmaceuticals, Inc.
• 7. Life Extension: Public Policy Aspects
• Bibliography
• Index