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By Michael Brickey, Ph.D., ABPP
The exponential growth in knowledge and technology
When you buy a computer, you discover that in less than a year it has been superceded by faster, better technology. Human knowledge, especially medical knowledge, is doubling every five years. 1 Computer chips for mapping genes double in power every 18 months. 2 CAT scans and MRIs, introduced in the early 1980s, have become as common as X-rays.
Twenty years ago, few would have envisioned commonplace use of personal computers or the Internet. In 1977 the President of Digital Equipment Corporation (DEC) told the World Future Society, “There is no reason for any individual to have a computer in their home.” 3 In 1983 Motorola launched the first mobile phone, a brick-sized phone with a small range and a price tag of several thousand dollars. At the end of 2006 there were 2.5 billion active cell phone accounts. Another half billion are expected to be added in 2007 and another half billion in 2008. Many of these tiny phones can also take pictures, text message and even play videos.
The next twenty years are likely to bring more technologies that will profoundly affect our lives in ways that are difficult to imagine now. The question isn’t whether but how. Medical researchers, pharmaceutical companies, and computer wizards will continue to dazzle us with new technology. The most profound new technology is likely to come from genetic engineering and gene chips. 4 The other profound technological growth will be in our understanding of how to optimally use and take care of ourselves mentally, physically, and spiritually. As with knowledge and lifestyles today, some people will use these wonderful resources wisely and some will not.
Richard Oliver gives a little perspective. He notes that the agrarian age lasted for about nine thousand years, the industrial revolution for 360 years and the information revolution is about to be superceded after 50 to 60 years. Taking its place will be the biotech revolution which “will last only about 15 to 30 yeas, but its economic returns will dwarf everything that has come before it.” 5
The coming breakthroughs in genetic engineering
Genetic engineering began in the early 1970s when scientists first learned how to isolate, clone, and “cut and paste” human genes. Genentech launched the first genetically engineered drug, insulin, in 1981. Insulin was created by cloning the human gene code for insulin and transferring it to bacteria which could be grown commercially. 6
In 1990 and 1991, three National Institute of Science researchers put copies of a missing gene into the white blood cells of a 4-year-old girl and a 9-year-old girl with severe combined immunodeficiency (SCID). With the gene missing, their bodies were not able to produce the adenosine deaminase (ADA), which plays a critical role in the immune system. SCID restricted their lives to a sanitized plastic bubble because they were so susceptible to diseases. The results of the gene implants were dramatic. 7 The girls were restored to health and appeared in press conferences two years later, happy and healthy.
In 1990 the U.S., England, France, Britain, and Germany agreed to collaborate to map the genetic codes of all human chromosomes. If you think of genes as the bar codes on products we purchase, the Human Genome Project is inventorying each bar code. The project was scheduled for completion in 2005 but finished in 2003. The ahead-of-schedule pace was due higher powered computers and a private firm, Celera Genomics, announcing it’s mapping in 2001. While this is an enormously complex undertaking, human genetic codes are far less complex than the Windows operating system in computers. 8 Windows has several million lines of code while the Human Genome Project found that humans only have 20,000 to 25,000 genes.
Battelle Memorial Institute, the world’s largest nonprofit research laboratory, had its staff predict the top ten technologies of the coming decade. First on their list was the Genome project. They noted that it is not the gene mapping per se, but the enormous commercial applications that make the technology profound. 9 Want to map some genes? While gene mapping equipment costs about $175,000 installed, there is now a do-it-yourself kit for $30,000 that will allow many more researchers to get into the business. 10
Genes are constantly being turned on and off like lights in a skyscraper. When on, they produce a hormone or enzyme that gives the body instructions. Genetic engineering will result in an inventory of which genes determine which diseases and what treatments are likely to be most effective. Eventually, physicians will use inexpensive disposable biochips to see what your genes are doing and help diagnose and treat your ailments or enhance your health. Daniel Cohen of the Centre d’Etude du Polymorphisme Humain predicts that by 2010, medicine will be able to genetically treat most serious diseases caused by a single gene defect and that by 2045, most common serious illnesses will be treatable with gene therapy. 11
In 2005 IBM completed building a family of super computers and software to study human proteins. Dubbed “Blue Gene,” 12 the project includes a computer 500 times faster than 1999 personal computers. Proteins are the building blocks of DNA, its messenger RNA, enzymes, and hormones. The project will be a huge boost to genetic engineering, tissue engineering, and hormone replacement therapies. IBM is now developing a supercomputer that can do 1,000 trillion calculations per second.
Genetic engineering
It is our increasing control over our genes and the deciphering of what certain gene products do that holds the best hope of retarding aging in the near future. –Gerontologist Steven Austad13
Genetic engineering involves modifying genes or their protein messengers (hormones or enzymes). Strategies include introducing genetic material that produces a desired protein, or blocks the action of problem genes, or mimics the actions of certain genes. One mechanism is to remove cells with defective genes, alter them, and put them back in the body. (This cut and paste strategy should be familiar to computer users.) Another common mechanism is to put genetic material on a benign virus or bacterium and introduce it into the body.
Companies owned by Novartis (the merged Ciba-Geigy and Sandoz pharmaceutical giants) are developing a TK (thymidine kinase) gene. 14 The TK gene is injected into diseased or cancerous cells. When the patient takes the medication gancyclovir, the gancyclovir kills the cancerous cells. Another application is with organ transplants. Transplants run the risk of the body’s immune system rejecting the transplant. TK can be inserted into the transplant organ. After surgery, gancyclovir is only administered if the patient is rejecting the transplant.
Genetic Therapy Inc. (a Sandoz subsidiary) is developing a genetic treatment for glioblastoma brain tumors. 15 The current treatment is surgery and radiation therapy but the tumor usually reemerges in about ten months. After surgery, Genetic Therapy’s approach saturates the tumor cavity, where some cancerous cells are almost always left behind, with a solution containing a virus derived from the herpes simplex virus which is encapsulated in a harmless retrovirus. (Retroviruses have RNA rather than DNA and an enzyme that allows them to transform their RNA into DNA.) The retrovirus only attaches itself to cells that are dividing. Hence they attach to the cancer cells. Patients are given an injection of the antiviral drug gancyclovir which interacts with the enzyme produced by the herpes virus and causes the dividing cells to die. Cells which are not dividing are not affected. The genes have been humorously dubbed “suicide genes.” The market is large, as 20,000 people in the U.S. and Europe die of brain cancer each year.
Arthropod-Borne and Colorado State University are working together on “antisense” technology. DNA has a pair of strands–the sense strand that produces RNA and the antisense strand which is a mirror image of the sense strand. (The function of the antisense strand is not understood yet.) With antisense technology the researcher or physician inserts copies of the antisense RNA into the body. The antisense RNA binds to sense RNA and blocks it from carrying out its mission of producing a protein that gives the body instructions. Their research is focusing on yellow fever and dengue fever. The approach is especially appealing because the gene only targets one set of genes and has no effect on other genes. Antisense therapy can also attach the engineered gene to the DNA so the RNA messenger molecules cannot read the DNA. Antisense has been successfully used with animals for problems like asthma. 16
Ariad Pharmaceuticals has a unique approach to protein deficiencies like diabetes. 17 After a corrective gene is implanted, the gene can be activated by taking a medication. In this way, the medication can activate the gene for a short period of time and produce the desired quantity of protein, e.g., insulin.
Dr. S. Gail Eckhardt is developing a process to treat head and neck tumors by injecting a common cold virus (with part of the genetic material removed) directly into head and neck cancers. The virus only destroys tumor cells with a missing or broken tumor suppressor gene, P-53. The P-53 gene is missing or broken in a high percentage of cancers, and almost universally missing or damaged in head and neck tumors. 18 Clinical trials with humans began in 1996.
Genentech’s Herceptin19 only acts on one gene, the HER2 gene. The HER2 gene prompts cell growth needed to maintain the body. Women with breast cancer, particularly the type that metastasizes, have additional copies of the HER2 genes and the extra copies cause cancerous growth. Herceptin binds to the HER2 cells and prevents the cells from dividing. Thus chemotherapy is often unnecessary.
In 1994 scientists reported they had transplanted a missing “LDL receptor gene” into the liver of a woman with an inherited disorder that caused her to have high cholesterol and rapidly developing heart disease. Her cholesterol level dropped and her arteries became healthier. 20
Researchers21 have also found a single gene in humans that suppresses cancer. When either gene of the gene pair is damaged or absent, there is a sharp increase in rates of malignant brain, breast, prostrate, kidney, and skin cancers. Consequently, the gene can help diagnose whether a cancer is benign or malignant. With further research, physicians might be able to replace or mimic the gene when it is missing or damaged.
Eventually physicians will be able to turn off many of the genes causing problems such as cancer or possibly even obesity. Mice whose RII-beta gene was removed were fed a 58% fat diet and remained trim and fit. 22 The gene’s effect is to increase metabolism and stimulate brown fat cells to convert calories to heat rather than to stored fat. The mice weighed 10% less than normal but had the same amount of muscle tissue. They ate slightly more than other mice and remained fertile and apparently normal. Other scientists have discovered a gene that they believe will lead to a weight loss medication for humans. 23
While it is beyond our focus, it is noteworthy that genetic engineering raises many ethical issues, including cloning, choosing the sex of a fetus, trying to design the perfect child (“brains and beauty” genes), whether the technology is universally available, denial of insurance coverage for people with diagnosed “defective” genes, and religious objections to intruding in God’s domain.
One of people’s biggest fears about aging is Alzheimer’s disease. In 1993 Duke University researcher Alan Roses identified four variations of a gene that is associated with Alzheimer’s. People with two apo-e4 genes are eight times more likely to develop Alzheimer’s and, on the average, their symptoms appear at age 68. People with one e3 gene have an average age of onset at 75. Those with e2 genes have a much lower risk of contracting Alzheimer’s. Researchers not only know what genes apparently effect Alzheimer’s, they have successfully immunized mice against Alzheimer’s disease. 2425 In 1999 researchers began small clinical trials of vaccinating people with mild to moderate levels of Alzheimer’s disease.
Historically medicine has focused on curing diseases and has paid far less attention to prevention. Within a few decades, physicians will probably be able to run health checks and identify and disable genes that cause Alzheimer’s, Huntington’s Chorea and other genetic diseases.
Biochips
Biochips combine computer technology and DNA research. Biochips have microscopic pieces of DNA chemically bonded to a silicon computer chip. When the chip comes in contact with blood or other tissue samples, it identifies patterns in the sample’s genes.
Affymetrix and OncorMed are jointly developing a computer chip that can examine a body cell and detect a malfunction in gene P-53, a gene thought to be a key contributor in 60% of human cancers. Research has indicated that women with breast tumors and mutated P-53 genes are in greater danger of metastasis and death than women with normal P-53 genes. The chip could identify which women have these high risk mutations. Physicians would recommend very aggressive cancer treatments for these women and conservative treatment for women with breast tumors and normal P-53 genes.
LeRoy Hood, Ph.D., at the University of Washington, is developing a biochip that distinguishes between slow-growing prostate cancers (that do not need treatment) and aggressive cancers for which surgery is essential. 26 He predicts that by 2010 a biochip will be able to recognize the distinctive gene patterns in the 20 most common types of cancer. Treatment would then be targeted to that particular type of cancer. Also, two researchers independently have identified the PTEN “tumor suppressor” gene that, when absent, contributes to the growth of prostate, breast, and other cancers. 27
Nanogen is developing diagnostic tests to identify different types of infectious bacteria. It will then track the effectiveness of various antibiotics in treating each type of bacteria. 28 With biochips your physician would test your cells or blood with an inexpensive disposable computer chip to determine the particular type of infection you have (based on which pertinent genes are turned on, turned off, or mutated). The pharmaceutical industry is well aware of the need to tailor medications to biochip diagnoses and is investing billions in joint ventures with biochip firms.
Tissue engineering
In 1995 newspapers and magazines carried a picture of a mouse with a human ear growing out of its back. 29 The mouse graphically illustrated advances in tissue engineering. Tissue engineering combines biological and engineering sciences to culture and transplant human and animal tissues. Tissue engineering closely matches the body’s original equipment, requires less surgery and medical care than alternative treatments, and is rapidly becoming the most cost-effective treatment. The initial focus has been on skin and cartilage tissues. Breast, liver, vascular tissues, pancreas, blood cells, heart valves, and other organ tissues are also being developed. 30 Research interest has included stem cells, which are immature cells that have the potential to develop into almost any tissue. Researchers are learning how to insert stem cells into parts of the human body to grow whatever tissue is needed. Chemotherapy kills stem cells that make new blood cells. Physicians are now able to remove stem cells before chemotherapy and grow them in the laboratory for subsequent transplantation. 31
Skin grafts have been grown and grafted onto burn patients since about 1990. Organogenesis Inc. is working on developing artificial skin from newborn foreskins. 32 The foreskin lacks the immune components that might lead to rejection. Foreskin contains both the dermis and epidermis layers of skin, making it ideal for skin transplants and burn reconstruction. A single foreskin can generate a square meter of skin.
In the U.S. there are 500,000 surgeries a year that require bone substitutes. Physicians often insert biodegradable “scaffolding” and bone cells grown in the laboratory. Carnegie Mellon University is developing a system that grows the cells in the lab and then uses CAT or MRI data when inserting layers of custom fitted scaffolding, vessels, and bone tissue into the patient. 33
Tissue engineering includes encapsulating cells that secrete hormones. CytoTherapeutics Inc., for example, is working on a process that injects encapsulated hormone cells near the spinal cords of individuals with amyotrophic lateral sclerosis (Lou Gehrig’s Disease). 34 The technology also might be applicable to diseases such as Parkinson’s, epilepsy, multiple sclerosis, and diabetes. It could also be used to replace glands that are removed by surgery or destroyed by cancer, e.g., gall bladders and thyroids. Scientists are working on encapsulated artificial liver cells. Eventually, bone marrow cells might be transplanted into the bones of hemophiliacs. 35 For pain management, cells that produce endorphins could be transplanted next to the source of the pain to counteract the pain. 36
There are waiting lists for organ transplants. In the U.S. alone eleven people a day die waiting for an organ. Nanotechnology (miniaturization on a microscopic scale) will result in more and more bioreplacement parts. 37 Two biotech firms, Nextram in Princeton, New Jersey and Imutran in Cambridge, England are racing to perfect organ transplants from pigs. 38 Pigs breed and mature quickly, have organs about the same size as human organs, and raise fewer objections from animal rights activists than monkeys would. The biggest concern is making sure the PERV retrovirus is not accidently transmitted to the donor and from the donor to others (c.f. the transmission pattern of the HIV virus).
Genes that control aging
More than 98% of human and chimpanzee genes are comparable but the chimpanzee longevity record is only 39 years. Only about 1,000 genes account for the differences between chimps and people. 39 This is one more indication that it is probably not necessary to alter very many genes to increase longevity.
Southern Methodist University (Dallas) researcher Raj Shoal4041 identified the enzyme in fruit flies that helps protect cells from free radicals. He gave fruit fly embryos an extra copy of the gene that produces the enzyme. The result was “super” flies that lived 30% longer than untreated fruit flies and were markedly more active, even in their “old age.” (Fruit flies have been a focus of genetic studies because of their large genes.)
Research with yeast, mice, and nematodes have found genes that can lengthen or shorten the aging process by turning them on or off or mutating them. (Nematodes are the phylum of worms that include roundworms, pinworms, hookworms, and the worm that causes trichinosis.) In 1996, geneticists extended the life of nematodes by 500% by removing one gene. Nematodes, which normally have a life span of nine days, lived more than two months. 42 The life span of mice was increased by almost a third by removing one gene. 4344 The missing gene did not appear to disturb their fertility or other functions.
In 1996, scientists discovered the gene that causes Werner’s syndrome, a rare inherited disease that causes premature aging. 45 The disease causes a 20-year-old to have gray hair and the health ailments of someone much older, e.g., cataracts, osteoporosis, and heart disease. Most people with Werner’s syndrome die before 50. This gene and the enzyme it triggers appear to play a vital role in how DNA repairs itself and reproduces and is a promising key to how genes program aging.
Telomeres are the extensions on the ends of chromosomes. They are composed of DNA material but do not appear to contain genetic codes. When chromosomes reproduce, the telomeres get shorter. In 1973, Calvin Harley46 proposed that telomere shortening was the mechanism that limits how many times a chromosome can reproduce. That limit is called the Hayflick effect after Leonard Hayflick, who demonstrated that most types of cells can only reproduce about fifty times. Michael Fossel, a neurobiologist and physician, believes that there are several ways to prevent telomeres from shortening and even ways to restore them to their original size, reversing the aging process and restoring youth. 47 He expects the first human trials by 2005 and widespread telomere therapy by 2015. 48
In 1997, articles in Science and Nature indicated that telomeres shrink and lengthen over and over as cells divide, and form a “buffer zone” to protect the DNA. 49 While this questions the simplicity of Fossel’s theory, it illustrates how research on telomeres is closing in on exactly how chromosomes work. After Nobel Laureate Thomas Cech identified the human gene that controls the telomerase enzyme, two teams of scientists have introduced the gene into human tissue in the laboratory and found the cells divided indefinitely (while untreated cells all eventually died). 50 Likely initial applications are in helping tissues heal faster.
Brown University researcher John Sedivy51 has identified a human gene that suppresses the number of times a cell can reproduce (the Hayflick effect). He grew human cells in the laboratory and “knocked out” (removed) the p21 genes. These cells had up to thirty more divisions than cells that still had the p21 gene. Eventually, physicians might be able to remove human cells, knock out the p21 gene and reintroduce the cells into the person’s body.
Hormone therapies
Hormone therapies are one of the most controversial areas of anti-aging medicine. Wyeth introduced Premarin in 1962 to help perimenopausal and menopausal women experience fewer menopausal symptoms and feel and function better. It was synthesized from pregnant mare’s urine and resembles but does not chemically match human estrogen. Wyeth promoted Premarin instead of a bioidentical estrogen so they could have a patented product that would generate larger profits than a generic.
Millions of women took Premarin or Prempro (Premarin+progestin). Over the years the public became increasingly aware of side effects. The huge blow came in 2002 when the Women’s Health Initiative abruptly terminated its large hormone replacement study after five years because researchers concluded the risks outweighed the benefits. Of particular concern were increased risks for beast cancer, blood clots, heart attacks, and strokes.
While some women find menopausal manageable, many find it a nightmare with distressing physical symptoms, mood swings, depression, difficulty with memory and concentration, and even feeling they are losing their minds. They were left with a choice between risky traditional approaches to hormone replacement, toughing it out, trying herbs and yams, or trying poorly understood “natural hormone replacement” products.
Who would have guessed that to the rescue would come—Suzanne Somers. Somers became famous as Crissy on the TV sitcom “Three’s Company.” She has always been very serious about health and fitness. When she developed beast cancer, she shared her story with the press and her decision to stay on bioidentical hormone replacements despite admonitions from many physicians who believed it would increase her risk of further cancer. Bioidentical hormones exactly match the chemical structure of human hormones. Her book The Sexy Years promotes the benefits of bioidentical hormones and has sold more than two million copies. Physicians have been deluged (and unprepared) for women asking for bioidentical hormone replacement. She has another book due in December 2007, Ageless: The Naked Truth about Bioidentical Hormones.
Ms Sommers likes to talk about the Seven Dwarfs of Menopause: Itchy, Bitchy, Sweaty, Sleepy, Bloated, Forgetful, and All-Dried-Up. Now that would make an interesting Disney movie. Briefly, she makes a convincing case that bioidentical hormones do not have the side effects and risks of Premarin and Prempro as they match what women’s bodies normally produce. Not only does it match nature, women taking them as directed continue to have monthly periods. The starting point is finding a physician who is knowledgeable, testing to determine one’s current hormone levels, and prescribing a combination of hormones (e.g., estroil, estradiol, estrone, progesterone, testosterone, and DHEA) that match one’s premenopausal levels. The emphasis is on what are normal levels for you and balance between the hormones. I am not a physician or expert in hormone replacement. I do think Ms Somers makes a good case that is worth considering and I do recommend her book.
Hormone therapy for women also reduces the risk of Alzheimer’s disease, osteoporosis, heart disease, and colon cancer. Consequently research on new generations of birth control/hormone replacement pills are being developed that will allow treatment to be more individualized to a woman’s health history. 52 Harvard scientists53 have given female mice an implant that keeps their ovaries from dying, thereby blocking the onset of menopause. They think the same method could easily be applied to women to eliminate menopause.
One of the reasons women tend to gain weight after menopause is that their bodies also stop producing testosterone, leaving the estrogen—testosterone ratio further toward the estrogen side. Some physicians are experimenting with small doses of testosterone supplements for women to counter weight gain, low energy, depression, and loss of interest in sex. 54
Research is also underway to develop “designer” estrogen replacement that will allow men to take estrogen without the feminizing effects (e.g., breast enlargement, increased ratio of fat tissue). This would help reduce men’s risk of heart disease and possibly Alzheimer’s disease.
In a 1990 landmark study, Daniel Rudman and University of Wisconsin researchers gave healthy men ages 61 to 81 a synthetic Human Growth Hormone (HGH). The injections reversed biological aging by twenty years with a 9% increase in muscle, a 14% decrease in body fat, a 7% increase in skin thickness, and increased strength, improved memory, increased vigor, and enhanced stamina. 55 This was without changes in diet or activities. The control group continued with normal aging. Based on Rudman’s results, the National Institute of Aging funded five million dollars of research at nine university medical centers. 56
Genentech developed recombinant human growth hormone in 1985 for treatment of children whose growth was stunted. A year later Eli Lilly developed a Human Growth Hormone that differed by one amino acid and exactly matched real human growth hormone. After a court battle, the two were given exclusive rights to manufacture human growth hormones under the Orphan Drug Act. The hormone has been used by tens of thousands of children. Khansari and Gustad57 report that injecting mice with growth hormone has greatly increased the mice’s life spans. Swedish researchers administered low doses of human growth hormones to humans and reported improved health with no side effects. 58 Klatz59 and Cranton and Fryer60 give several case histories of people who are taking human growth hormones and achieving results similar to the Rudman study. Chein and Terry61 report using human growth hormone with 800 patients with none of the patients having any major side effects. While Human Growth Hormones are achieving impressive results, they are not likely to be widely used because they have to be injected and are very expensive (about $10,000 a year). There also is very justified concern about side effects (joint swelling and pain, fluid retention, insulin resistance, and high blood pressure), long-term use, and what happens if discontinued.
Secretagogues (pronounced suh-CREE-ta-gogs) are chemicals that cause other organs to secrete substances. The term is often used to refer to chemicals which cause the pituitary gland to produce growth hormones. Secretagogues have been used with abnormally short children to prompt more normal growth. Merck (pharmaceutical co.) has commissioned studies of secretagogues with adults. While generally secretive about progress, they do report that elderly people who have used their medication, MK-677, have increased muscle mass, an increased sense of well being, and sleep better. 62 Secretagogues can be taken in a daily pill form, making it more palatable and less expensive. Secretagogues are preferred to HGH as they prompt the body to release HGH in a more natural pattern. Thus, a pill to “turn back the clock” is in human trials with a major pharmaceutical company. Six major pharmaceutical companies are developing secretagogues. The Internet has about a hundred secretagogue products that purportedly prompt the body to produce HGH. Eventually, consumers will have good data on the pros and cons. Currently I would be very skeptical of claims.
As men age, their testosterone levels decline and their bodies tend to lose muscle tone, gain weight, and have lower sex drives. Low testosterone is also associated with heart attacks, depression, Alzheimer’s disease, and osteoporosis.
Testosterone therapy for men has only been popular for a little over a decade. Millions of men are taking testosterone supplements, usually in a topical gel. The Institute of Medicine concluded, “The trials that have been conducted do not show definitively that there are benefits of testosterone therapy for older men…the committee recommends short-term efficacy trials to determine if there are benefits of testosterone therapy in older men.” The Life Extension Foundation is critical of the Institute’s research design and lack of any protocols to block the conversion of testosterone to estrogen. 63 Anecdotal reports are tricky as I would expect testosterone supplements to be especially prone to placebo effects. Thus, even if testosterone supplements had no benefit, I would expect at least one in three men to say they helped. The most natural way to increase testosterone levels is exercise, particularly exercise emphasizing strength.
One problem with testosterone or DHEA supplements is that men’s bodies often convert testosterone to estrogen. An alternative strategy, whether taking testosterone treatments or not, is to block the conversion of testosterone to estrogen. Men’s fat tissue contains the enzyme aromatase, which converts testosterone to estrogen. Like women, with age men’s estrogen-testosterone ratio loses on the testosterone side. Obese men have an even bigger problem because of their higher levels of aromatase. Conversion to estrogen can be blocked with aromatase-inhibitors (prescription medication) or with over-the-counter supplements such as zinc, chrysin, nettle-root, and quercetin. 64
Another factor is sex hormone binding globulin (SHBG) which circulates in the blood stream and can bind testosterone, making it unavailable. Consequently, physicians test free testosterone levels to see how much is really available. SHBG levels are affected by nutrition, other hormones, and the liver’s ability to excrete SHBG.
There are a number of commercial products being hyped to improve memory. These have to be viewed very skeptically. Most probably only give placebo benefits unless you happen to have a deficiency the product happens to correct. There is a lot of university and pharmaceutical company research on medications that would enhance memory. Gary Lynch at the University of California–Irvine has identified a class of biochemicals, ampakines, that do appear to improve memory in humans, especially older people. 65 His 54 human subjects showed remarkable improvement in pre/post testing on word games, mazes, and photograph recognition tasks. Young men improved scores by 20% and men over 60 improved their scores by 100%.66 The change was rapid and short-lived. Cortex Pharmaceuticals has a pill form of the substance under the trade name Ampalex. 67 Genetic engineering has had several examples of enhancing memory and intellectual functioning in animals. Antioxidants have shown considerable promise in preventing the mental deterioration that goes with aging68 and in improving memory. 69 University of Saskatchewan researchers70 working with mice have been able to stimulate new nerve growth in the hippocampus (an area deep in the brain that is associated with memory). Two research teams have used genetic engineering to increase the intelligence of mice by inserting a gene. 71
One of the mechanisms of aging is glucose cross-linking with proteins. Cross-linking makes tissue rigid and gives it a yellowish or brownish color. The process affects our bones, joints, teeth, kidneys, the lenses of our eyes, and, of course, our blood vessels. In our blood vessels the glucose links with cholesterol. This causes a narrowing of the arteries, which increases blood pressure, increases the risk of a stroke, and impedes blood from getting to its destinations. The cross-links were thought to be almost impossible to break. A new drug, Timagedine, however, breaks the cross-links. It is in clinical trials and showing promising results. If it or a comparable medication is successful, it will be possible to undo much of the damage, and stiffness, that at least until now has come with aging.
Another mechanism of aging is cumulative damage caused by free radicals (unattached electrons, usually oxygen, looking for a meaningful relationship with atoms). The 1990s brought a much greater understanding of how certain food, vitamins, and supplements help combat free radical damage. These include: vitamins C, E, and B-12 (folic acid), selenium Coenzyme Q-10, lipoic acid, phytochemicals, flavonoids, and carotenoids. Researchers have found that excess iron is one of the most pernicious sources of free radical damage. Consequently it is being removed from many multiple vitamins. (Iron, however, is especially needed by menstruating women, people who give blood, and people with certain types of anemia.) Many current centenarians did not have the benefit of daily vitamins, much less the more tailored vitamin and supplements available today. Vitamin C supplements, for example, have been found to reduce the incidence of advanced cataracts by 80%.72 A National Institute of Aging study73 found vitamin E supplements delayed the progression of Alzheimer’s disease by seven months. Vitamin B-12 and B-6 supplements have reduced heart attacks in women by half. 74 The examples could go on and on.
Researchers75 have identified nitrones–antioxidants that trap free radicals and prevent brain damage–that not only prevent antioxidant damage to brain tissue, but reverse damage in mice. When injected with the chemical, old mice performed as well on mazes as the young mice. The treatment prevents the plaque build up found in Alzheimer’s disease. The researchers indicate that the treatment should be applicable to people. While it wouldn’t necessarily extend life spans, it would improve the quality of life.
In the early 1990s men who had difficulty getting erections were injecting a vasodilatory drug into their penises. Then Pfizer (pharmaceutical company) introduced Viagra. Now seven million American men are taking sixty million pills a year to help them obtain erections. 76 Viagra of course has competition from Levitra and Cialis.
Since 1960 death rates from heart disease and stroke have been reduced by more than 50%. Even the common colds and flus might be curtailed by a new medication, Pleconaril, 77 which is showing promise in clinical trials. Plenconaril works by disabling the virus that causes colds and flus and meningitis.
You don’t have to look old
Crowns and tooth implants are making it possible for virtually everyone who practices good oral hygiene to have teeth that last a lifetime. Grandmother might have had dentures at 50 but you can have permanent teeth at 150.
Millions of people wear contact lenses instead of glasses. Radial keratoplasty and photorefractive keratectomy offers surgical correction for some forms of nearsightedness to 250,000 Americans a year. 78 Cataract surgery and cornea replacement is more than 25 years old. For people who have lost their vision, researchers have inserted tiny photochips with sixty electrodes into retinas. The images are fed by a wireless miniature camera on the person’s glasses. Currently the chips just give a very crude sensation of light and movement. The next generation will have 500 electrodes. 79 Scientists are also experimenting with cochlear implants that might eventually help people with hearing impairments hear better.
Plastic surgery was once just for movie stars. In 2005, 1.4 million Americans had cosmetic surgeries. The average surgeon’s fee was less than $5,000. The most common plastic surgeries in the US in order are: liposuction (fat removal), breast augmentation, blepharoplasty (eyelid surgery), rhinoplasty (nose shaping), and abdominoplasty (tummy tuck).
Face lifts and abdominal reshaping are becoming increasingly sophisticated, safer, and less intrusive each year. Skin care products are helping skin stay resilient longer. Skin cells are being cloned and grown in laboratories for burn victims needing skin transplants. This research will help scientists learn how to help facial skin that has lost its resiliency. Skin creams are in clinical trials that dissipate wrinkles and greatly speed the healing of scars and skin blemishes.
The obvious hair plugs in hair transplants in the 1970s have been replaced by very sophisticated surgeries. While Minoxidil (Rogaine) and Propecia have only shown modest results in growing hair, pharmaceutical companies know the pay off for a medication to grow hair will be enormous and they are investing millions. Gene researchers have been able to activate resting hair follicles in mice by inserting a gene. 808182 While at a very rudimentary stage, researchers83 were able to transplant sheaths surrounding hair follicles from the scalp of a man to the arm of a woman who had an incompatible blood and tissue type. Her arm then grew head hair with xy (male) chromosomes. Key to the success was eliminating parts of the tissue that would prompt an immune system rejection, including making sure there were no blood cells in the transplanted sheath. Someday a hair cell, that was transplanted from another person, might make a great plot twist in a murder mystery novel. Meanwhile, good hair pieces can look very real and provide protection from the sun.
Fitness training has become a science. Trainers have become much more sophisticated about how to exercise to obtain the desired strength, aerobic, and flexibility results. Gyms, spas, trainers, home exercise equipment, television programs, and videotapes make very effective exercise within the reach of almost everyone.
Resolving the nutrition puzzle
Common sense says that nutrition plays a significant role in longevity. The literature on nutrition, however, is a tower of Babel. The U.S. government says eggs and red meat are evil and a few years later says they aren’t so bad. Even moderate coffee, chocolate, and alcohol have been blessed in research findings. One author advocates a vegetarian diet while another wants high protein and still another prescribes diets by body types or blood types. Linus Pauling says everyone needs thousands of units of vitamin C each day while the U.S. Government says the recommended daily allowance for adults is 60 mg. Then there are true believers who claim that a particular vitamin or supplement is the critical secret to longevity. Other than avoiding extremes, it’s hard to know what to believe. The good news is that research on nutrition is developing a much better understanding of the relationship between nutrition and metabolic processes, hormones, and neural transmitters.
Research on centenarians has found that most lead fairly normal lives and do not follow special diets or take magic pills. They have a wide variety of eating habits and do not go on diets. About the only clear nutritional distinctions between them and people with shorter life spans is that they have kept a stable body weight throughout their life, are physically fit, and do not smoke. Biographies also suggest that most tend to eat a wide variety of foods. Personality traits such as independence, self-reliance, optimism, dealing with problems, using their minds, and having a sense of purpose appear to be more important than what they eat. Reuben Andres’ extensive study of mortality patterns challenged conventional wisdom by finding the lowest mortality rates among people who were 10% over ideal body weights and higher mortality among those 10% underweight. 84
Mind over matter Drug trials have to include a placebo (sugar pill) because, on the average, one-third of the response to medications is due to expectations (the placebo effect). The “mind-body” literature is replete with case histories of people who had terminal cancer, changed their lives, and lived for many years. Robert Dilts85 helped his mother achieve this when her physician told her to “get her affairs in order.” He relates that he began his research by seeking literature on people who survived cancer. The medical librarians told him they did not have any data on that until he finally came up with the term “remission.” Re-mission is an apt word as many survivors made major changes in their lifestyles and developed a new mission in life. Herbert Benson describes the role beliefs and religion can play in health and healing. 86 Bernie Siegel describes how mental health can be critical in beating cancer. 8788 The mind-body literature is also replete with case histories of people who suffer a loss, such as the death of a spouse, lose their “will to live” and die despite good health before the loss. Depression, stress, worry, anger, resentment, and dealing with loss all can take their toll. Effectively dealing with emotions, frustration, and loss are essential to longevity.
Old isn’t what it used to be Our society offers scripts for what to expect as we age. Traditional scripts are to retire at 65, face progressively deteriorating health, and become irrelevant. Traditional scripts do not include living past one hundred or living a vital life much past 70. Challenges to conventional thinking are starting to appear in our culture, like a New York Times Magazine special issue titled “Funny We Don’t Feel Old.” 89 As Baby Boomers age, such articles are becoming increasingly common as are phrases like “50 is the new 30.” Unless you have a clear vision of an alternative, it is easy to get sucked into the conventional expectations. Today, to be a centenarian is to be an oddity. The president and Willard Scott send birthday greetings. The newspaper may run an article and ask your “secret” for longevity. In a decade or two it won’t be so unusual.
The U.S. Census Bureau estimates for the number of centenarians at:
75,000 in 2000
170,000 in 2010
299,000 in 2020
477,000 in 2030
659,000 in 2040
1,208,000 in 2050. 90
The aging of our population will create profound shifts in what we think of as old.
People who are centenarians in the 1990s survived very hard times. Only 50% have pension incomes and 12% are on public assistance. 91 More than 60% have less than an eighth grade education. By the year 2015, however, only 10-15% of centenarians will have less than an eighth grade education. 92 Better educated people tend to be more resourceful, have more financial resources, and be more attentive to their nutrition and health. Our increased education, prosperity, and health and beauty products will make for greater stamina and kinder, gentler physical aging. Demographic studies have found that chronic disability rates among Americans over 65 have declined 1-2% a year since 1982, when the surveys began. 9394
Beliefs and expectations are factors too
Everyone knew that no one could run a 4-minute mile because the human body just wasn’t capable of doing it. Roger Bannister95 believed it could be done and used different training regimens, strategies, and beliefs than other runners used. Within a year of his breaking the 4-minute mile barrier in 1954, 37 other runners ran a mile under 4 minutes. New records have been established 17 times and dozens of high school students have run the mile in less than 4 minutes. The current record is 3 minutes and 44.39 seconds. Just wishing something does not make it so and just wishing for a long, vital life doesn’t make it happen. Beliefs about what happens to people as they age, however, can become a self-fulfilling prophecy that limits our longevity. Like Roger Bannister, we need to believe it is possible to do something most people don’t think can be done–to live to 150 or longer. Like Roger Bannister we need to develop strategies to achieve new milestones.
Can you really live to be 150? In the late 1950s Leonard Hayflick found that cells appear to have a biological clock that limits the number of times each cell can divide. His research convinced many scientists that human cells had a longevity potential of 115 years. Even when cells stop dividing, they don’t necessarily die. Their DNA continues to give instructions and make proteins. 96 Recent research has shown that some cells divide more than others and that genetic engineering can greatly extend the number of cell divisions. As Deepak Chopra97 points out, Hayflick’s studies of aging of cells in test tubes and petri dishes ignore the profound influence that thoughts, feelings, actions, and hormones play in aging vs. longevity. Researchers98 have been able to add telomerase to human tissue in the laboratory and enable it to reproduce indefinitely (so far 165 times which is more than three times the normal limit). The concern has been that it might prompt cancer but so far the cells are cancer free.
Researchers are skeptical about reports of people in remote areas living over 120 years. Many such claims to longevity are difficult to document because records of the births would be over a hundred years old and hard to locate if records ever existed. Two of the best documented “oldest old” are Jeanne Calment, a French woman who lived 122 years and Izumi Shigichio, a Japanese man who lived 120 years.
Life expectancy tables give extrapolated estimates of the age at which half of the newborns born in the designated year would have died. In the U.S. the life expectancy has risen from 49 in 1900 to an estimated 78 in 2007. The Japanese have a longer life expectancy of 80. Those who have already survived childhood and part of adulthood have even longer life expectancies. Barring a plague worse than AIDS, the average life span is likely to continue to climb. These data are averages and include infant deaths and people who sabotage their longevity with alcoholism, drug abuse, cigarette smoking, obesity, and other self-destructive behaviors.
If you are a reasonably healthy adult who does not engage in these self-destructive behaviors, your life expectancy will be well beyond the 76-year figure. The number of American centenarians has been doubling every ten years. Statistics tell us that the distribution curve for longevity is not likely to abruptly stop at age 115 but have a tapering tail into even older ages.
These statistics, however, are like looking in a rear view mirror as they are based on the lifestyles and health resources of previous generations and do not take into account current and future medical advances and other advances that add to longevity.
Assumptions about life expectancy and maximum life span are likely to be blind sided by paradigm shifts and new technology. There have always been scientists who made pronouncements about limits and things that can’t be done, e.g.,
The world won’t be able to feed any more people because population increases in a geometric ratio and the ability to produce food only increases in an arithmetic ratio. (Thomas Malthus in 1798 when the world’s population was one billion as opposed to six billion two hundred years later. 99)
Man will never fly.
Electrons are the smallest particle possible. (That is until quarks were discovered.)
Man is the only animal that uses tools. (Jane Goodall disproved this when she observed chimpanzees using sticks to “fish” for ants. 100)
Cloning is just science fiction. (Baa says Dolly, the world’s first cloned sheep. 101102 In 2000 we even had bulls that were clones of cloned bulls. 103)
Computers can’t think. (This one is still open to debate but the computers are closing in on the distinction.)
There are numerous instances of medical “facts” changing. To cite a recent few: 104
Stomach ulcers are caused by stress. (While stress contributes to ulcers, medical researchers have determined that ulcers are caused by helicobacter bacteria. Physicians are now successfully treating ulcers with antibiotics.)
Sugar makes children, especially hyperactive children, hyper. (While there might be some individual cases in which this is true, clinically “blind” studies have convincingly shown no significant increase in activity from sugar.)
Finally, there are beliefs about aging that do not square with current research, e.g.:
If you live long enough, you will get Alzheimer’s disease. (While credible projections from the 1994 Canadian Study of Health and Aging predicted that virtually anyone over 100 would have Alzheimer’s, the projection did not square with research on centenarians. Most centenarians do not have Alzheimer’s disease. 105 Perls106 reports that if you make it to 100 you apparently are not at risk for getting Alzheimer’s.
Your brain stops growing after puberty. (Research with mice is clear that stimulating environments effect a flurry of dendrite growth, making new connections in the brain and that physical exercise helps the brain grow blood vessels. 107 Research published in Nature in 1996 demonstrated that adult rats in enriched environments developed 15% more neurons in their hippocampal cells. 108)
IQ declines dramatically starting around age 20. (Many of these conclusions were derived from tests that compared older generations with current generations. Older generations, however, had far less education and stimulation than current generations. Further, many of these studies failed to exclude people who had health and mental conditions, e.g., Alzheimer’s. When these design problems are eliminated, test scores were stable or even improved on many tests until age 60. At 60 researchers started seeing great variance in scores among test takers. Healthy, flexible, better educated individuals continued to do well while less educated individuals were more likely to lose skills. I presume that research would also find that people who continued to read and learn throughout their life did especially well. How good are you at remembering a telephone number you just heard for the first time? Beard109 had 166 centenarians take a Digit Span test (which is part of the most respected intelligence test). When asked to repeat back a series of numbers, 78% of the centenarians could remember and repeat 4 numbers, 60% 5 numbers, and 38% 6 or more numbers. Two centenarians even remembered and repeated 8 numbers. Generally, older people could do things about as well as they used to but couldn’t do things as fast as they used to or couldn’t do as many things simultaneously as in the past. On the other hand, they had a much richer knowledge base. To make a comparison with computers, their hard drives had a lot more data and programs but their operating speed (megahertz) was slower than the ever faster new computers. Also keep in mind that pre/post IQ data are pretty old data. Today’s health and medical advances might yield much better performance for older people in the future.) In one of the studies, with excellent methodology to control for complicating variables, 70% of participants did not show cognitive decline when retested five or seven years later. These were all individuals over age 65. The 30% who did show decline had atherosclerosis of the carotid arteries (which go to the brain), peripheral vascular disease, diabetes, and/or the APOE e4 gene which is associated with Alzheimer’s disease. The e4 gene also appeared to accelerate decline for all of these conditions except for atherosclerosis. The e4 gene, of course, is under intense study for genetic engineering and other interventions.
You lose 100,000 brain cells a day–never to be replaced, leading to cognitive deterioration with aging. (Even if this were true, the brain has a trillion neurons and in a 150-year life span you would lose less than 1% of your neurons. MRI scans, however, have found that the data were erroneous for people in good health. The earlier studies were flawed by limited instrumentation and by including people with Alzheimer’s and other brain diseases. Harvard professor Marilyn Albert110 followed subjects from their teenage years and found four factors that correlated with good brain functioning: education, physical activity, lung function, and self-efficacy. Research published in Sciencein 1996 reported that while neurons and their myelin coverings might shrink, there is little loss of cortical neurons in normally aging human brains–a much more hopeful state for interventions. 111)
Japanese and Swedes live longer than Americans. (They have a longer average life expectancy because the U.S. has rather high infant mortality rates and somewhat higher death rates until middle age. American adults who reach 80, however, live one or two years longer than Japanese, Swedes, French, and English counterparts. 112)
Each year you age you are at greater risk of disability or death. (Studies in several countries have found a decline in the mortality rates starting at around age 100, i.e., a person has better odds of making it from 110 to 111 than he or she did of making it from 90 to 91. 113
Thin is good, overweight is bad. Reuben Andres114 found that the Metropolitan Insurance tables used for ideal weight are too liberal with young adults and too strict with adults over 40. Adults over 40 or 50 who were 10%-20% overweight according to Metropolitan Insurance tables had lower mortality rates than their age counterparts who weighed less. Heymsfield and Allison115 found that adults over 70 who were 20 pounds, even up to 50 pounds over ideal body weights did not have increased mortality rates while thin adults, even with those with identified diseases excluded, had higher mortality rates.
Economists and futurologists lament that centenarians will bankrupt Medicare and Social Security. A U.S. Health Care Financing Administration study found that the average medical expenditures for the last two years of life for centenarians was $8,300 while the average medical expenditures for the last two years of life for people who die at 70 is $22,600. 116 Grim predictions of economic age warfare also ignore that fact that many centenarians continue to contribute to society with paid or volunteer work.
Getting older is depressing. To the contrary, studies have found that people become happier with age. Between ages 18-27, 28% of Americans reported being very happy. The percentage went up with age with 38% between 68-77 reporting being very happy. 117 Robert Browning had it right when he said,
Grow old along with me! The best is yet to be.
The last of life, for which the first was made.
–Robert Browning
Longevity data are a little like autopsies–people have to die before you can gather the data. The data don’t take into consideration medical advances and lifestyle. Thus, longevity data are always out of date before the data are issued. Looking at the rapid growth of medical treatments and prevention, great gains in longevity appear inevitable. This leaves you with choices. You can choose to base your assumptions about your longevity on:
the technology that is available to you now and will be available to you in the future
-or-
the state of health and technology of previous generations
the lifestyle and mental edge you can live to enhance your longevity
-or-
average people’s lifestyles and thinking
reports of healthy, vital, active centenarians
-or-
conventional “wisdom” about people over 65 losing their memory, not having sex, and “going downhill fast”
The idea of living to 150 years or more used to require a leap of faith, much like a religious person who says she can’t prove God exists but has faith. If she were wrong in taking that leap of faith, she would just be dead anyway and had lived a good life. If she is right, she has a heavenly reward. If you believe you will live to 150 and are wrong, you would just die at an earlier age than you hoped (but probably still older than if you had not tried). If you are right, you will live well and long with extra decades to contribute and participate.
With the incredible scientific leaps of knowledge, living to 150 is no longer a leap of faith. The question is not whether, but when and who. You can choose to pretend that science will take a holiday and will not produce any advances to improve longevity and quality of life. Or you can choose to base your life decisions on resources you already have and likely scientific advances that can greatly enhance your life. For those who choose the mental edge and take advantage of resources, the data support the very real possibility of healthy, vital living to 150–and even longer.
Think of all you’d derive just from being alive
And this is the best part, you have a head start
If you are among the very young at heart
–J. Richards and M. Carr’s song, Young at Heart
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