The Longevity Factor Chapter 1 The Origins of Life
In the beginning God created the heaven and the earth. And the earth was without form, and void…. And God said, Let the waters bring forth abundantly the moving creature that hath life… and every living creature that moveth…: and God saw that it was good.

—GENESIS, CHAPTER 1

On the last day of February 1953, students and faculty members from the Cavendish Laboratory at England’s University of Cambridge were having lunch at the Eagle pub, drinking Green King beer and enjoying the bar, with its graffiti from World War II airmen. At the top of the lunch hour, Francis Crick, a thirty-seven-year-old physicist turned biologist who had not yet earned his PhD, bounded in and loudly announced to his colleague, the zoologist turned geneticist James Watson, “We have found the secret of life!” Indeed they had. That morning, the two young scientists had deciphered the structure of deoxyribonucleic acid (DNA)—two strands of sugar connected by paired molecules called bases—an accomplishment for which they would later win the Nobel Prize.

That structure, a “double helix” that can “unzip” to make copies of itself, was the finding that confirmed that DNA carried the hereditary code of life. Crick and Watson immediately published their findings in the scientific journal Nature, and capped a rather academic, dry account of DNA’s structure with one of the most famous understatements in the history of science: “It has not escaped our notice that the specific pairings we have postulated immediately suggest a possible copying mechanism for genetic material”—that is, of life.

Fifty years later, in 2003, another landmark paper appeared in the same prestigious international journal, also from a Cambridge laboratory, but this time in Massachusetts. The head of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard Medical School, David Sinclair, and his associates published a paper entitled “Small Molecule Activators of Sirtuins Extend Saccharomyces cerevisiae Lifespan.” A year later, another peer-reviewed journal, Molecular Microbiology, published their follow-up article, “Small Molecules That Regulate Lifespan: Evidence for Xenohormesis.”

Sinclair explained that certain plants can increase production of specialized molecules during times of stress, such as drought or increased ultraviolet radiation from the sun. When consumed by animals, these plant molecules, which Sinclair called xeno factors, were found to interact with the animals’ genes and impart amazing health benefits. Most astonishing was the observation that these laboratory animals lived substantially longer—in some cases, up to 50 percent longer—than their average expected life span. Tests for cell damage indicated that they were also much healthier, with fewer occurrences of cancer, heart disease, and brain cell deterioration than is normally seen with aging (see figure 1).

This discovery, which has since been confirmed in laboratories at MIT and the University of California, San Francisco, is revolutionizing our ideas of how and why we age. Because human DNA has important basic similarities with animal DNA, we also possess similar genes that can be activated by eating these specialized plant molecules. For the first time in human history, there is real evidence that we can use this process to slow aging and live not only longer but healthier.
In the Beginning
When I considered that the same stressed plant molecules could prolong life in yeast (evolutionarily approximately one billion years old), fish (500 million years old), and mammals (200 million years old), I became perplexed. What could possibly be the biological connection between the lowly yeast and humankind? To solve this scientific conundrum, I found myself going farther and farther back in time, asking more questions. What are the most basic molecular factors that all living things have in common? And is there a common biological language that makes all cells form, grow, function, reproduce, and die?



FIGURE 1 Extension of life span by xeno factors.

This incredible story of discovery may well begin with the formation of the universe nearly 14 billion years ago, when all the matter, energy, and space in what is now the observable universe were contained in a single infinitely dense point. From that point came a cataclysmic, fiery explosion commonly referred to as the “big bang” (see figure 2), in which space expanded and particles of the embryonic universe formed. These particles coalesced to form the billions of galaxies that now make up the universe, including our own Milky Way, with its own billions of stars.

After the big bang, incomprehensible amounts of heat and radiation were released and subatomic particles were formed—including protons, neutrons, electrons, quarks, and baryons—all of which would become the building blocks of life as we know it. This material cooled until approximately 4.5 billion years ago, when the earth was formed. Initially, as recorded in Genesis, water did completely cover the globe. There was no oxygen, only intense cosmic radiation, turbulent seas, volcanic eruptions, and frequent meteoric bombardments from outer space. During the next billion years, primary elements needed to support life were formed, including carbon, oxygen, nitrogen, phosphorus, sulfur, magnesium, calcium, copper, and iron.



FIGURE 2 The big bang theory explains that a cosmic explosion at the beginning of time expanded space containing matter in all directions. As this matter cooled, gravity and pressure allowed atoms to form into elements and eventually into the planets and stars we see today.
The Origin of Life
It was indeed from the waters that life on our planet began. Charles Darwin, in 1871, made the suggestion that the original spark of life may have begun in a “warm little pond with all sorts of ammonia and phosphoric salts, light, heat, and electricity present, so that a protein compound was chemically formed that was ready to undergo still more complex changes.” These changes led to a crucial step in the formation of life: the development of a more complex molecule that was itself capable of reproducing itself. The latest research now indicates that ribonucleic acid, or RNA—a molecule similar to DNA—may have been the first complex molecule on which life was developed. Like DNA, RNA contains genetic information, but it also performs chemical reactions, like some proteins. But proteins cannot reproduce on their own; that was the amazing feat accomplished by RNA.

RNA is the common ancestor that has given rise to the major cell lines of life. The first of these belongs to a type of bacteria called prokaryotes, which lack a cellular nucleus. Bacteria that are two to three billion years old have been discovered in ancient rocks from Australia. They have survived throughout the millennia due to the simplicity of their design and their ability to become dormant for long periods at a time.

The second cell line is the eukaryote. These cells contain a cell nucleus, separated from the rest of the cell by a membrane; this nucleus is where the cell’s DNA is housed. The word eukaryote, which derives from ancient Greek, refers to the “true nucleus.” Eukaryotic cells are the basic building blocks of all animal life, from single-celled organisms like amoebas to complex human beings. Interestingly, fungi, mushrooms, and yeast also have eukaryote cell types; this is why the study of yeast cells has been found helpful in understanding many human cellular functions.

Cells of the third type, the archaebacteria, a subset of prokaryotes, have been referred to as “life’s extremists.” These cells inhabit some of the most forbidding and remote environments on the planet, including the depths of hot springs, or extremely alkaline or acidic waters. They live in the mud of marshes and at the very bottom of the ocean, and they thrive in places hostile to all other life-forms.

The first animal cells appeared about 1.5 billion years ago, single-cell organisms that were able to reproduce. Protected by a cell membrane formed of protein and fats, they were also able to use raw materials that could be converted into energy, and to respond to changes in environmental temperature, acidity, or nutrient levels. These reactions were facilitated by specialized reactive molecules called enzymes.

Enzymes, which we will learn more about, are specialized proteins that act as catalysts and can help alter and form other more complex proteins and nucleic acids that make up RNA and DNA. They are critical to the function and survival of all living things. In his research, David Sinclair discovered one specific enzyme critical to longevity.

With the formation of algae and multicellular structures like jellyfish and plankton, the stage was set for the evolution of higher organisms. Yeast was formed approximately 900 million years ago. Although for thousands of years it was used for fermenting alcohol and making bread, yeast wasn’t known to be a living organism until Louis Pasteur confirmed it in the 1860s. Yeast subsequently played a critical role, as we shall see, in the study of aging. Six hundred million years ago, the first animals, invertebrates such as sponges, jellyfish, worms, and insects, made their appearance on our planet. Plants eventually evolved from ancient green algae and populated the earth approximately 400 million years ago, shortly before the appearance of vertebrate animals about 380 million years ago (see figure 3).

After the abrupt eradication of the dinosaurs about 65 million years ago, following a dramatic drop in the earth’s temperature, mammals began to proliferate, leading to the appearance of our humanlike ancestors approximately 2 million to 3 million years ago. Modern humankind is but a flash in the evolutionary night, being approximately 400,000 years old, with a recorded history less than 15,000 years old. Carl Sagan put this in perspective when he speculated on the evolution of human intelligence in his book The Dragons of Eden. He constructed a timeline in which the period from the big bang to the present moment was represented by a 365-day calendar year. In that scenario, all of recorded human history occupies the last ten seconds of December 31; the time from the waning of the Middle Ages to the present would occupy little more than one second.

Although our time on earth as a species is so short, there is a corollary to this. Since all the constituents that would eventually come together for our embodiment were present in the big bang, we really trace our lineage to a moment 13.7 billion to 15 billion years ago. Since all matter derives from that initial burst, each of us is formed of the same primordial dust that subsequently became stars; every living thing carries within it elements that evolved and reconstituted until they finally formed what we are today.



FIGURE 3 The evolutionary tree and timeline from the formation of earth to modern man showing the common genetic linkage of yeast, worms, fish, mice, and humans.
The Timeline of Human Evolution
Why is this lineage so crucial to our story of how we can activate our genes to live longer and healthier by ingesting specific stressed plant products? Because it demonstrates how the various life-forms on earth synergistically coevolved throughout earth’s multibillion-year history, making them intimately dependent on one another for survival. Most important, the genetic code that provides for the survival of bacteria and yeast is written in the same biological language that articulates the biochemistry of a human being. Scientific studies, therefore, conducted on these early forms of life may indeed be extrapolated to human beings, thanks to our shared DNA. Through the science of phylogeny, which studies relationships of DNA between species, we know that both plants and animals activate similar genetic mechanisms to survive in response to adverse conditions such as excessive heat, drought, and famine.

The concept of xenohormesis is based on the premise that our bodies have developed the ability to read and react to molecular cues from the plant world during times of environmental stress or adversity. By ingesting certain nutrients from environmentally stressed plants, we genetically activate our body’s defenses to survive. This survival response results in cellular changes in our body controlled by genes and mediated by enzymes that can shift our everyday metabolism of sugars so that now we can use our stored fats as an energy source.

The survival response triggered by these plant molecules also causes the activation of animal mitochondria, the structures within the cell that act as powerhouses, or energy producers, allowing the mitochondria to release a larger amount of energy. Ultimately, stressed plant molecules—xeno factors—can stimulate health and enhance immune defenses in the animals that consume them, increasing the viability of those animals in a stressful environment. This strengthening effect is what David Sinclair and others have now confirmed both by documenting less disease and increased longevity in laboratory animals, and by isolating the genetic mechanisms at work.

This discovery is the by-product of yet another new scientific field heralded by Watson and Crick, molecular biology, which attempts to unravel the biochemistry of life’s beginnings and the vast molecular web of interaction between plants and animals. In the last fifty years, more has been discovered about the secrets of both plant life and animal life than in the previous 15,000 years of recorded history. Since the early 1990s, researchers at the forefront of molecular biology have taken a Neil Armstrong–like “giant leap for mankind” toward finally unraveling the secrets of life—and how to prolong it.