Chapter OneTHE ICU:
A NEW ANTIAGING RESEARCH LABORATORY
The day had dawned cold and gray with a lowering sky on the morning of February 16. The dark, angry waves of the Long Island Sound dashed against the rocks, a harbinger of worse to come. Another snowstorm was scheduled for New York and Connecticut, making the winter of 2010 one for the record books from Florida to Maine. Escaping to the tropics was on my mind, but duty called.
This was the day I was turning in the manuscript for my new book, Forever Young. I was proud to have written a book that broke new ground yet apprehensive, because the science might be considered cumbersome. I knew that there was no other way to tell the story. People needed strategies to stop the deadly degenerating signs of aging, and I feel it is important to explain my recommendations, which are all scientifically based.
As I nursed a cup of green tea and read the news on the Internet, a 24-point-type headline from the United Kingdom’s Financial Times caught my eye: “Scientists discover the secret of ageing.” The article explained how one of the biggest puzzles in biology—how and why living cells age—had been solved by an international team based at the United Kingdom’s Newcastle University. Using a complex “systems biology” approach, the researchers, in conjunction with scientists from the University of Ulm in Germany, had set out to discover why cells become senescent, or, in other words, grow old. The research, published by the journal Molecular Systems Biology, showed that when an aging cell detects serious DNA damage, which may be the result of general wear and tear from daily living, it sends out internal signals. These distress signals trigger the cell’s mitochondria, the energy-producing part of the cell, to make free-radical molecules, which instruct the cell either to destroy itself or to stop dividing. The reason for this is to avoid the damaged DNA that results in cancer.
As you will discover in these pages, I am convinced that the damaging diseases and cellular destruction associated with aging begin with the mitochondria. I concur with the research findings from Newcastle University, as they validate my own research regarding how and why we age. The release of this study just as I was delivering my manuscript to my publisher was very exciting, because the researchers’ discovery echoes the underlying theme of this book.
I have gone beyond the science of why we age to search for practical ways to intervene in the process. In Forever Young you will learn new, effective, and safe strategies to protect the mitochondria, the mitochondrial DNA, and other parts of the cell from this programmed cell death, known as apoptosis, starting with the miraculous therapeutic powers of niacinamide (vitamin B3), which you will read about on page 107.
A New Model for Understanding Aging
My first experience with seriously ill patients occurred when I was a medical student at Michigan State University College of Medicine. During my rotation in internal medicine, particularly the weeks spent in the intensive care unit, I became intimately familiar with sepsis, one of the most common causes of death.
Also known as gram-negative bacteremia and gram-positive bacteremia, sepsis occurs when infectious agents like bacteria or fungi or products of infection like bacterial toxins enter the body, most often through a wound or incision. If this systemic infection goes unchecked, it leads to a condition known as septic shock, resulting in hypotension, or extremely low blood pressure; dysregulation of blood sugar; and the failure of such multiple organ systems as the heart, kidney, liver, and lungs.
The Sepsis/Inflammation/Aging Connection
In 1981 when I was in medical school, I was trying to understand what caused underlying damage to the vital organs during septic shock. The question was a huge challenge for both physicians and scientists. The research indicated that metabolic changes occurring on a cellular level were the primary cause of organ dysfunction and failure. The consensus was that these fundamental metabolic disturbances were the result of inadequate tissue oxygenation and a disruption of the body’s ability to control blood sugar levels. This combination of symptoms came to be known as multiple organ dysfunction syndrome, or MODS. It was widely hypothesized that multiple organ dysfunction syndrome resulted from tissue hypoxia, a condition in which vital organs do not get enough oxygen to meet their needs. Fast-forward to a new millennium: the concept of inadequate oxygen levels to vital organs as the fundamental cause of MODS is now being seriously questioned.
Today, scientists believe that adequate oxygen is delivered to the vital organs by the bloodstream during sepsis and septic shock. The problem is that the cells are unable to use that oxygen, even though it is being supplied at adequate levels. The inability of the vital organs to utilize oxygen is a cellular malfunction in the tiny organelles known as the mitochondria. This impaired cellular oxygen problem is termed cytopathic hypoxia. Just as cytopathic hypoxia is far more important in the generation of MODS than had ever been thought in the past, I propose that cytopathic hypoxia, as seen in the cellular changes of aging, is far more important to the degeneration of the organ systems than was previously believed.
Having come to that conclusion, I had to ask the next question: If cells cannot utilize the oxygen, where in the cell is the defect? The answer is the mitochondria.
The Mighty Mitochondria
The mitochondria are tiny energy-generating parts of the cell. They function as microscopic furnaces, converting food into fuel, and are responsible for all energy production in the body. The majority of the oxygen supplied to the cell is utilized by the mitochondria to make a chemical known as adenosine triphosphate, or ATP. ATP is the energy storage and transfer molecule that is essential to life. As I discussed in one of my previous books, Dr. Perricone’s 7 Secrets to Beauty, Health, and Longevity, functioning mitochondria are vital to maintaining a healthy body and beautiful skin.
A Closer Look at Mitochondrial Function
Although tiny, the mitochondria play a huge role in the body as the energy-producing portion of the cell. To accomplish this feat, they consume 90 percent of the oxygen that is needed by our bodies. As mentioned, this oxygen is used to oxidize fuel or burn food to synthesize ATP, which is the energy currency of the cell. This process of ATP production in the mitochondria is known as oxidative phosphorylation and takes place in the part of the mitochondria known as the electron transport chain. Within the electron transport chain, ATP is produced in five steps. If anything disrupts this chain, free radicals are created; this further disrupts the electron transport chain, causing irreparable damage to the mitochondria. Damage to the mitochondria and disruption of the electron transport chain are the first events seen in sepsis. Unchecked, this results in total systemic collapse, multiple organ failure, and death.
Although it may seem counterproductive, the energy produced by the mitochondria is the major source of free-radical production in the cells. This is a result of the metabolic process that converts food and oxygen to water and ATP. As energy production takes place in the electron transport chain, within the mitochondrial membrane, about 5 percent of the electrons escape. This creates free radicals that damage both the mitochondria and the cell.
Note
FREE-RADICAL CHEMISTRY
Many people are confused about free radicals. They know that they are bad and that antioxidants combat them. Understanding the chemistry of free radicals will give you an important perspective on aging.
Atoms and molecules are most stable when there is a pair of electrons circulating in their outer orbit. When a molecule or atom loses one of the electrons, it becomes a free radical. Its mission in life has now become the quest for another atom or molecule to hook up with. Any substance that rips electrons away from another molecule is known as an oxidizing agent or electrophile. Free radicals can damage tissues, cell membranes, and DNA, disrupting our store of genetic information, which may lead to the initiation of certain cancers.
Free radicals can also oxidize the fats that make up the cell wall membrane and the membrane covering the mitochondria and the nucleus. This oxidation can lead to cellular dysfunction and serious damage to the immune system and major organs such as the brain, heart, kidneys, and pancreas. Free radicals contribute to at least fifty major diseases, including atherosclerosis, heart disease, rheumatoid arthritis, and lung disease, as well as accelerated aging. Although free radicals exist for only a fraction of a second, the inflammatory cascade that they generate goes on for hours or days.
Antioxidants, including vitamin C, alpha-lipoic acid, and Co Q10, are known as reducing agents. They neutralize free radicals and leave a much more benign antioxidant free radical in its place. Unfortunately, the mitochondria are a site of constant free-radical production (see page 6) and very susceptible to the damage that free radicals can cause. If we hope to preserve youthful function and prevent disease, it is critical to search for agents and antioxidants that will protect the mitochondria from free-radical damage.
Therapeutic Strategies for the Mitochondria in Disease and Aging
Although the concept that free radicals are responsible for triggering an inflammatory response on a cellular and molecular level was considered with skepticism when I introduced it in The Wrinkle Cure, it is now dogma accepted by even the most conservative scientists. The idea that free radicals and inflammation cause cellular...
