From Here to Immortality: Anti-Aging Medicine

The symptoms are disturbing. Weight gain, muscle aches, fatigue and joint stiffness. Some experience hearing loss and diminished eyesight. In time, both memory and libido will lapse, while sagging skin and incontinence may also become problematic. It is a malady that begins in one’s late 40s, and currently 100 percent of baby boomers suffer from it. No one is immune and left untreated; it always leads to death. A frightening new disease, virus or plague? No, it’s simply a fact of life, and it’s called aging.

The mythical fountain of youth has long been the subject of folklore, and although it is both natural and inevitable, human beings have been resisting the aging process for centuries. The early Greeks were the first to theorize that aging was a disease resulting from an imbalance of internal fluids. From there, alchemists, shamans and snake-oil salesmen have all preyed on the desperate and the gullible, promising to turn back the clock — for a price, of course.

A Brief History of Anti-Aging Medicine

In the 1930s and 1940s, scientists began taking a more serious and academic look at the root causes of aging. Common theories of the day included the idea that genetic mutations cause physiological deterioration. Then, in 1961, anatomist Leonard Hayflick (dubbed the father of modern anti-aging research) proved that cells do in fact have a finite life and that in laboratory tests, cells from older people die more quickly than those from younger people. This discovery gave rise to the theory that humans have an internal “clock” that could possibly be reset in order to slow the aging process.

In the last 30 years, theories of aging have come and gone. In a paper presented to the Los Angeles Gerontology Research Group at the UCLA School of Medicine, Dr. L. Stephen Coles, MD, PhD, identified 25 current theories of aging, with most falling into one of two schools of thought: the school of chance and the school of grand design.¹ The first theorizes that wear and tear is the main cause of aging; in a nutshell, the body simply wears out due to use, abuse and deterioration. The second theory states that after a certain period of time, our bodies trigger a genetic code that slows repairs. Support for this theory can be seen in simpler organisms in nature like lobsters, coral and sponges, which show no signs of aging at all. The fact that they show no signs of deterioration suggests that some evolutionary change must have occurred as creatures became more complex.

In 1993, a landmark study by Cynthia Kenyon, PhD, at the University of California, San Francisco, found that mutations in a single gene could double the life span of Caenorhabditis elegans, a type of small worm often used in genetic studies. This one single finding provided the first step in proving the gene expression theory of aging and sparked a wave of research for extending human life span.²

Shifting Attitudes Fuel a Booming Industry

The notion that aging requires treatment is based on a belief that becoming old is both undesirable and unattractive. In the last several decades, aging has become synonymous with deterioration, while youth is increasingly revered and admired. Anti-aging medicine is a relatively new but thriving field driven by a baby-boomer generation fighting to preserve its “forever young” façade. According to the market research firm Global Industry Analysts, the boomer-fueled consumer base will push the U.S. market for anti-aging products from about $80 billion now to more than $114 billion by 2015.³

So, what exactly is anti-aging medicine? Traditional doctors such as endocrinologists and geriatricians are specifically trained to treat age-related conditions, but anti-aging as a medical specialty is not currently recognized by the American Board of Medical Specialties, meaning doctors can’t officially be board-certified in it. But, that has not stopped the field from founding its own professional society, the American Academy of Anti-Aging Medicine (A4M). Founded in 1992, A4M boasts some 24,000 members worldwide and offers a certificate in anti-aging medicine, available to any MD.³ In its mission statement, the academy says the disabilities associated with normal aging “are caused by physiological dysfunction which in many cases are ameliorable to medical treatment, such that the human life span can be increased.”

Anti-aging enthusiasts such as the A4M contend that life spans can be prolonged through interventions such as hormone replacement therapy and dietary supplements, while critics say many anti-aging interventions are ineffective or possibly even harmful. Mainstream organizations such as the National Institute on Aging recommend consumer skepticism when it comes to anti-aging products and treatments. “Our culture places great value on staying young, but aging is normal,” the institute says. “Despite claims about pills or treatments that lead to endless youth, no treatments have been proven to slow or reverse the aging process.”³

But one of A4M’s co-founders, Robert Goldman, a doctor of osteopathic medicine, contends that much of the resistance to the anti-aging movement comes from sectors of the health and pharmaceutical industries that feel threatened financially by the increased use of products like nutritional supplements. “It all has to do with who’s controlling the dollars,” he says.³

Is Aging Optional?

It is one thing to slow the progression of aging, but it is another thing entirely to begin rejuvenating life at the cellular level. According to one renowned British gerontologist: “Aging is emphatically not an inescapable destiny.” Aubrey de Grey, author of the book Ending Aging, became interested in the field of  regenerative medicine more than a decade ago. De Grey’s work is influential and far-reaching; his institute has established a scientific prize for extending the lives of mice by rejuvenation or other means. The Methuselah Foundation provides cash rewards to researchers who surpass past performance regarding the life span of mice; the highest performance to date is 1,819 days in January 2012 (life spans for mice in the wild average one year).⁴

But critics argue de Grey’s theories are radical; he believes that within 30 years, it may be possible to rejuvenate a 50-yearold individual to such a youthful condition that he/she will live to the age of 130. He also contends that comparable rejuvenation technology for a mouse may be discovered within 10 years. His theories are based on the idea that the key to rejuvenation is the repair of seven distinct kinds of damage that represent aging: cell loss; cell senescence; extracellular protein cross-linking; nuclear DNA mutations; mitochondrial DNA mutations; and the accumulation of “garbage” inside, as well as outside, cells. After extensive research, de Grey developed a seven-step plan designed to curb the identified specific organic damages linked to age dubbed Strategies for Engineered Negligible Senescence (SENS),4 even co-founding a foundation by the same name. The foundation, headquartered in Mountain View, Calif., describes itself as the “only nonprofit currently prioritizing a regenerative medicine approach to the diseases of aging.”

At the heart of its efforts, SENS funds the research and development of new classes of medicines called “rejuvenation biotechnologies.” Rejuvenation biotechnologies are targeted therapies that apply the principles of regenerative medicine across the entire scope of the damage of aging. In other words, instead of merely slowing down the accumulation of aging damage in our tissues, rejuvenation biotechnologies will remove, repair or replace the damaged cellular and molecular machinery. This means that with every round of therapy, a person’s eyes, heart, arteries and bones will not just suffer less ongoing degradation of their structures, but will actually become more youthful and healthier in their structure and function, as the fine cellular and molecular order of these and other tissues are progressively restored to their youthful integrity. SENS Research Foundation is actively funding and performing research to develop, promote and ensure widespread access to these innovations, promoting the training of young scientists in this new approach, and disseminating rejuvenation research into health research and biotechnology institutes and biotechnology nationwide. Its stated goal? To “reimagine aging and open up lives of vigor and health set free from the gravitational pull of time.”⁵

Breakthrough Studies Show Promise

Can a pill that slows the aging process really be in the pharmaceutical pipeline? Some researchers say yes. Based on numerous studies, a growing consensus states that we are closer than ever to an innovative crop of drugs that will significantly extend human life spans. One recent report says the first could debut in just five years.

Landmark work led by an Australian researcher and published in the March 8, 2013, issue of Science demonstrates that a single anti-aging enzyme in the body can be targeted, with the potential to prevent age-related diseases and extend life spans. The paper shows all of the 117 drugs tested work on the single enzyme through a common mechanism. This means that a whole new class of anti-aging drugs is now viable, which could ultimately prevent cancer, Alzheimer’s disease and type 2 diabetes.⁶

The target enzyme, SIRT1, is switched on naturally by calorie restriction and exercise, but it can also be enhanced through activators. The most common naturally occurring activator is resveratrol, which is found in small quantities in red wine, but synthetic activators with much stronger activity are in development. “Ultimately, these drugs would treat one disease, but unlike drugs of today, they would prevent 20 others,” says the lead author of the paper, Professor David Sinclair from UNSW Medicine, who is based at Harvard University. “In effect, they would slow aging.”⁶

The drugs in development will be administered orally and/or topically. While any drug would be strictly prescribed for certain conditions, Sinclair suggests that one day they could be taken orally as a preventative. This would be in much the same way as statin drugs are commonly prescribed to prevent, instead of simply treat, cardiovascular disease.⁶

Gene therapy is another exciting field of study. A team of scientists led by Ronald DePinho at Harvard University has managed to control the aging process by targeting specialized structures at the tips of chromosomes called telomeres. When the researchers genetically engineered mice to have short telomeres, mice aged prematurely. When they used gene therapy to lengthen telomeres, the reverse happened. Aging, infertile mice with shriveled testes and diminished cognitive abilities began to revive. DePinho has estimated that, overall, the mice went from being what was essentially ages 80 to 90 in human years to the equivalent of middle age in the course of the experiment.⁷

In other studies, scientists have found that feeding aging mice rapamycin — an immunosuppressant that is used to prevent organ rejection after transplants — can extend the life span of mice significantly. Researchers say the drug seems to improve the functioning of mitochondria, structures that generate power for cells. Previous research has shown that mitochondria dysfunction is involved in numerous diseases of aging.⁷

The Stem Cell Connection

In early May, a team of Harvard Stem Cell Institute scientists announced the discovery of a protein that circulates in blood that causes old, enlarged hearts to revert to a more youthful size and functionality. The study, performed with mice, could lay a foundation for a new approach to therapy for a common form of heart failure that strikes the elderly. “The change was unbelievably obvious,” says Dr. Richard T. Lee, a cardiologist at Brigham and Women’s Hospital and one of the leaders of the study. “Usually, we do quite sophisticated quantitative analyses of hearts and the shapes of the cells and things like that. … You could see what happened from the very first experiment.”⁸

In another recent study, researchers at the University of Pittsburgh Medical Center genetically altered mice to make them age faster, making them old and weak in a span of 17 days. The scientists then injected the mice with stem cell-like cells taken from the muscle of young, healthy mice, reversing the aging process. The rapidly aging mice lived up to three times longer, dying after 66 days, rather than 28 days. The cell injection also appeared to make the animals healthier, improving their muscle strength and brain blood flow. Dr. Laura Niedernhofer, one of the study’s authors, says even though the injection of young cells didn’t necessarily rebuild the bodies of the mice, it did seem to improve their body health. “The young stem cells seem to secrete something that is quite beneficial,” says Niedernhofer.⁹

And, in Georgia, researchers have shown they can reverse the aging process for human adult stem cells, which are responsible for helping old or damaged tissues regenerate. The findings could lead to medical treatments that may repair a host of ailments that occur because of tissue damage as people age. A research group led by the Buck Institute for Research on Aging and the Georgia Institute of Technology conducted the study in cell culture, which appears in the Sept. 1, 2011, edition of the journal Cell Cycle. “We demonstrated that we were able to reverse the process of aging for human adult stem cells by intervening with the activity of non-protein-coding RNAs originated from genomic regions once dismissed as nonfunctional ‘genomic junk,’” says Victoria Lunyak, associate professor at the Buck Institute for Research on Aging.¹⁰

The “Real Age” Factor

A recent slew of popular books and websites claim that individuals can calculate their “real” age by answering a series of questions regarding their own habits, health history, chronic conditions, weight, blood pressure, family history, etc. Participants can then determine if their biological age is older or younger than the age on their driver license.

Dr. Michael Roizen is an internist and anesthesiologist and co-founder of RealAge Inc., a consumer health media company and provider of personalized health-management tools, as well as chairman of the RealAge scientific advisory board. He serves as chief wellness officer and chairman of the Wellness Institute at the Cleveland Clinic. Roizen’s popular RealAge website spotlights 149 factors, from weight, cholesterol and blood pressure, to drinking and driving, talking on a cell phone while driving and using birth control, that all influence longevity. While these types of surveys are more anecdotal than scientific, proponents say they can have a positive influence on anyone hoping to add years to their life —or life to their years.

“There are actually 190 factors that influence aging, but 149 that you can change,” Roizen says, noting that while people cannot change the genes they inherit from their parents, they can change the activity of those genes. Roizen refers to research looking at the glutathione S-transferase mu 1 (GSTM1) gene, which he says fights breast and prostate cancer. For example, the authors of one study found that by eating four servings a week of broccoli, men reduced their risk of prostate cancer because of the vegetable’s effect on the anticancer gene.

Besides dietary changes, Roizen claims lifestyle choices and personal habits can also boost longevity, with habits like regular exercise and flossing topping the must-do list. “Virtually anyone can live to age 90 with the quality of life that they had at age 45,” says Roizen. “San Francisco is built on fault lines. Whether it survives a magnitude 2.9 or 8.9 earthquake without damage depends on its building codes and how rigorously they’re enforced. We’re all built with fault lines in our genes, but whether we live to 90 or 100 with the quality of life of someone who is 45, or whether we die at 68 living with a disability and [at the real age] of someone who is 90 depends on our choices.”¹¹