Medical challenges and promises
The path to longevity encounters many obstacles, including the need to reset the body's built-in "regeneration clocks" that currently limit the number of times each cell can reproduce itself. Like an old car or building, parts of the body begin to wear out before we reach the end of our life spans. Skin tissue loses collagen, begins to wrinkle, and stops replacing itself. Joints become arthritic or simply wear out, requiring replacement. Plaque builds up in our brain tissue, clogging the neural pathways and contributing to degenerative diseases such as Alzheimer's that eventually rob us of our very identity and social connections.
The good news is that research into slowing aging and expanding life is in full swing. One of the first longevity genes was discovered in the tiny roundworm. In 1993, researcher Cynthia Kenyon was able to double the roundworm's life span by making a single mutation in the daf-2 gene, just one of the 19,000 genes in this nematode's genome. Such mutated nematodes not only live longer, but also live healthier. This single mutation in daf-2 has far-reaching effects on the worm's metabolism, its response to environmental stress, its ability to fight infection, and its control of damage by free radicals.5 The end result of these cellular effects is a remarkable slowdown in aging.6 Since the discovery of daf-2, scientists have located other longevity genes in yeast, fruit flies, mice, and rats. They have also identified human counterparts of these genes, giving hope that they can be targeted to possibly extend the life span of humans. Based on empirical results obtained from various animal models, researchers hope to extend human life by 30% or 40%, while at the same time reducing the disabilities of old age.
Caloric restriction, also described at times as a starvation diet, is another active area of research. It examines how reducing the consumption of calories (while still eating nutritionally balanced meals) slows aging and increases life span in mice, rats, dogs, and primates. Animals who start such a diet at a young age increase their life span 30% to 50%. Calorically restricted animals exhibit much higher activity levels, experience fewer common diseases such as cancer and heart disease, and appear more youthful and energetic overall. They spend the last part of their lives in relatively good heath, without the major infirmities of aging. One major downside in some animals, however, is a loss of fertility (as happens with very underweight female athletes). Scientists have known about the benefits of calorie restriction for nearly 70 years, but how it works has only come to light in the last decade. In yeast and worms, the SIR2 gene seems to influence longevity. Researchers have identified a similar gene in flies, mice, and humans.
Few humans would voluntarily sign up for a 1,000-calorie-per-day diet for the unproven promise of living considerably longer. So, pharmaceutical companies such as Sirtris, Novartis, and Elixir are designing compounds that mimic the effects of mutations in the SIR2 gene. These companies look for drugs that affect the activity of the Sir2 protein and related proteins called Sirtuins. One such compound, resveratrol, exists in red wine. Feeding resveratrol to yeast, worms, or flies extends their life span about 30%.7 The hunt is on for even more potent compounds that could slow the ravages of aging further while at the same time treating diseases associated with aging, such as Type 2 diabetes, cancer, and cardiovascular decline.
We expect to see much more research aimed at slowing, or perhaps even reversing, the aging process. These investigations run from basic molecular bench science about the biology of aging, to epidemiological research on the traits and life styles of centenarians, to animal studies of the kind mentioned earlier. Researchers continue to explore important avenues and report promising advances that could extend human life to 120 or beyond:
- Replacements for aging cells—The ability of embryonic stem cells to morph into almost any type of cell, from heart to liver or brain cells, holds the promise that they can replace damaged, diseased, or destroyed cells. This includes cells lost as part of the normal aging process, as well cells damaged by stroke or heart attacks. Scientists have cloned many therapeutically important proteins in the laboratory, including insulin and human growth hormones, to replace our own hormones. Eventually, this will lead to tissue regeneration and perhaps the replacement of entire organs.
- Improved diagnostics—The sequencing of the human genome and the continual improvements in this technology have made it possible to find the single nucleotide polymorphisms (SNPs) that represent alterations or mutations in our genes. These distinctive gene alterations are important because they could affect our susceptibility to disease. By 2025, millions of SNPs could be linked to some of the most vexing diseases, such as cancer, heart disease, Alzheimer's, and Parkinson's. Diagnostics based on this wealth of genome information could become common. (See Appendix C, "Complexity of the Genome," for more information.)
- Targeted preventive therapies—Better genomic information could lead to more effective therapeutic and lifestyle interventions, such as changes in diet prescribed to prevent the onset of disease. In more complicated diseases, bioinformatics is already paying dividends by assessing the role of genetics and both environmental and lifestyle factors. Owning your own genetic information on a microchip will become so affordable in the future that many people can practice preventative medicine by starting individualized therapies at earlier ages, as suggested by their genes.
- Snap-in knee joints—In Paoli, Pennsylvania, arthroscopic surgeon Dr. Kevin Mansmann has been working on materials and procedures to enable arthroscopic insertion of replaceable pads to cover worn surfaces in bone joints, in the knee and other joints. Even if they wear out, these synthetic components could be easily replaced with a surgical procedure that could become routine.
- Fantastic nano-voyage—Novelists and screenwriters have mused about taking a robotic 'fantastic voyage" through the human bloodstream. Nano devices, which operate at a scale of 1/1 billion meters, likely will be inserted into our bodies as sensors and biochips. One day, nano-robots may have the capability to detect, clean, or repair damaged blood vessels or organs from the inside, like a mini medical roto-rooter.
- Altering genes—Researchers are using molecular medicine to unlock the secrets of the aging process itself, by trying to uncover the genes involved. In the field of plant genetics, developers of the first genetically engineered plant (the Calgene tomato) were able to keep the tomato fresh longer by shutting down the gene that causes the tomato to rot and release its seeds. If scientists can do this with tomatoes, perhaps they can manipulate aging genes in humans, whether rotten or not.
In an era in which body parts can be replaced as they wear out, we need a new way to think about aging itself. Will there come a day when someone asks your age and you respond by saying, "I was born 91 years ago, but my knees are 16, my heart is 20, and my kidneys are 14 years old"? Like an airplane in which most parts have been replaced, with only the basic main frame still being original (but repaired and reinforced in places), how do we assess its real age?