Since the beginning of recorded history, humans have searched for the key to immortality and eternal youth. From the epic of Gilgamesh, recorded on clay tablets around 2000 B.C., to Ponce de Leon's famed search for the fountain of youth in the new world, the extension of life has been a recurring theme for humanity.
Today, scientists are coming closer than ever to making real medical breakthroughs that will “cure” aging and eventually bring an end to natural death. Pharmaceutical discoveries, and advances in the fields of nanotechnology, cloning, stem cell research and cryonics offer tantalizing glimpses at a future free from old age, and the ability to actually reverse the aging process itself - possibilities that life extension experts feel could become a reality by 2019. Of course, along with these discoveries come ethical questions about the meaning of life in the absence of death and the fate of religion, as well as concerns about overpopulation, boredom and why anyone would really want to live forever.
If the claims of life extension proponents sound far fetched, consider the fact that the average human lifespan has doubled since 1900 and continues to increase. Enormous medical advances occurred during the 20th century, resulting in the development of medications and technology that were once unthinkable. Less than 100 years ago, insulin was unknown and type 1 diabetes was a fatal and mysterious disease. Now, insulin is an inexpensive and easily obtainable drug that saves lives every day. Other medical devices that are common today, like internal pacemakers and contact lenses, were unthinkable just 100 years ago, and the rate of medical and scientific advances continues to increase.
In humans, like all mammals, aging begins almost as soon as we reach physical maturity. In fact, with an average lifespan of 70 years and maximum verified lifespan of 122 years, a typical person today spends the majority of their life aging. In biological terms, aging can be defined as an accumulation of damage to macromolecules like DNA, as well as cells, tissues and organs. The differences in life span between species are determined by genetics, differences in the ability to repair damaged DNA, as well as differences in antioxidant enzymes and free radical production. The science of life extension seeks to exploit these differences and alter the biological pathways involved in aging, with the ultimate goal of immortality. In this feature, we'll discuss some of the most promising approaches in life extension science.
Chemical Life Extension
resveratrol-pictureFor years it's been common knowledge that drinking red wine (in moderation) is good for your heart. What we didn't know was why. Then, in 1992, a chemical named resveratrol was suggested as the cause of the cardioprotective properties of wine. Unfortunately, you'd have to drink hundreds of bottles of wine each day to consume enough resveratrol to see a significant effect, so work on a pharmaceutical form of resveratrol was begun. Researchers have since shown that resveratrol extends the lifespan of yeast1, but studies in other species have had conflicting results. A 2008 study on mice found that while resveratrol causes changes in gene expression that are similar to those caused by dietary restriction and mice had fewer signs of old age, unfortunately they didn't live any longer than typical mice2.
In 2008, pharmaceutical giant Glaxo Smith Kline purchased Sirtris, the company which is developing a proprietary form of resveratrol, for $720 million dollars. Their product, SRT501 is now in Phase 2 clinical trials, and could be available in as little as 6 years. It will be years though, before we will know whether resveratrol will extend the human lifespan.
The latest discovery is a naturally occurring substance found in the soil of Easter Island, in the southeastern Pacific Ocean. Rapamycin has shown to extend the life expectancy of laboratory mice by up to 38% . Professor Randy Strong, of the University of Texas Health Science Center, said: "We believe this is the first convincing evidence that the ageing process can be slowed and lifespan can be extended by a drug therapy starting at an advanced age."
Another leading researcher Dr Arlan Richardson was quoted as saiyng "I never thought we would find an anti-ageing pill for people in my lifetime; however, rapamycin shows a great deal of promise to do just that."
Despite the recent hype, there is not yet conclusive evidence and a UK expert has warned that it can suppress immunity.
Therapeutic cloning and stem cells
To some researchers, therapeutic cloning is the most practical approach to life extension because compared to other methods, current technology for cloning is much more advanced. We already know how to make stem cells, and are learning more constantly about how to direct them to form different types of cells. In order to clone the cells of a patient and create a new organ or tissue, the process starts by taking a donor egg, and replacing its nucleus with the nucleus from a patient's cell, creating an embryo. The new cell is then be stimulated to divide, and after a few days, at the blastocyst stage of development, there are stem cells available to collect.
These brand new stem cells have the ability to turn into any type of cell in the human body, like muscle, blood cells or nerve cells. Scientists grow them in a culture dish, and are working to learn what chemicals or other instructions to add to tell them what type of organ or tissue to form. Ultimately, these newly formed, specialized cells will be injected into patients to heal damaged body parts, or used to grow whole new organs. One possible application of this process is to make bone marrow from stem cells and then inject them into the body. The bone marrow cells would find their way into the patient's bone marrow, and the new cells could rejuvenate many parts of the body.
Scientists have already had success growing simple organs and tissue from stem cells in laboratory experiments. This work is being accelerated by the Armed Forces Institute of Regenerative Medicine or AFIRM, which is a $250 million initiative in cooperation with researchers at Wake Forest and Rutgers that is using soldiers' own stem cells to grow skin, muscles, tendons and bone. It will take more research, but scientists hope to be able to clone more complex organs like hearts in the future.
Nanotechnology
Some of the biggest advances in life extension may come from the microscopically small products of nanotechnology. Nanotechnology is the building of precise structures on an atomic or molecular scale. Ultimately, scientists hope to build molecular machines or robots that will revolutionize both medicine and manufacturing.
In the field of life extension, theoretical nanotech treatments include chromosome replacement therapy. In chromosome replacement therapy, a nanofactory would produce perfect new chromosomes based on the patient's own genome. Special nanorobots carrying these new chromosome sets would be injected into the patient. They would the travel to cells, extract the exisiting chromosomes and replace them with new copies, effectively eliminating age related DNA damage.
While complex nanorobots are merely theoretical at this point, other nano tecchniques that could impact the quality of human life are already proven to be useful in animal models. For instance, a technique called nano neuro knitting has been shown to be effective in helping to repair severed nerves in the brains of mice3. Proponents of medical nanotechnology believe that medical nanobots capable of extending life will be available by the 2020s.
Caloric Restriction
In order for humans alive today to see the full benefits of life extension science, we need to live long enough to see further advances in the field. Today, caloric restriction is the most well documented method for increasing lifespan, and it is the only dietary method that has been shown to improve the mean and maximum lifespan of a variety of species, from yeast to dogs. In fact, in rats, calorie restriction was shown to double life span 70 years ago4.
Caloric restriction involves consuming a severely reduced calorie diet while still consuming adequate quantities of vitamins and minerals. Scientists are currently working to extend their knowledge about caloric restriction to primates. While we don't yet have proof that caloric restriction will increase the human lifespan, we do know that it lowers cholesterol, fasting glucose, and blood pressure5.
While the methods by which caloric restriction increases lifespan are unclear, theories include both increased and decreased oxidative stress, decreased insulin and decreased free radicals. Regardless of the answer, caloric restriction won't make us immortal, but it just might help us live long enough to see the benefit of other life extension techniques. Some people are already using calorie restricted diets like the Okinawa diet and the CRON-diet.
Cryonics/Cryogenics
While most people tend to avoid contemplating their own death, a few people are choosing to use cryonics or cryogenics to preserve their bodies after death. Although there are no guarantees that cryonics, the process of warming and then reviving and treating a patient who's body has been preserved at extremely cold temperatures, will ever become a reality, some feel that the cost of cryonics is a small price to pay for the chance to live again in the future.
The purpose behind cryonics is to slow metabolism and the process of decay using extremely low temperatures, in hopes that one day we will discover a way to treat the patient's cause of death. While people have been cryogenically frozen since the 1960s, no person or mammal has ever been revived from cryogenic temperatures. One of the many obstacles to successfully using cryogenics is learning how to repair the damage caused by ice crystals formed within cells. While improving freezing techniques to reduce cell damage is certainly a goal, researchers hope that in the future we will also have the ability to repair damage done by past and present freezing techniques.
Conclusion
Life extension proponents view aging as the ultimate disease and they aim to find a cure. They feel strongly that this cure will be discovered within our lifetime. However, life extension is not without controversy.
Many opponents of life extension approach the concept from a religious or philosophical perspective, worrying about the value of life without death, and how a lack of natural death would impact the true meaning of life. In many ways, this argument falls along religious lines, with people who believe they will be rewarded in the afterlife standing opposed to life extension. On the other hand, people who are less certain about what happens after death tend to see little harm in enjoying life for as long as possible, in case this life is all we get. Many on both sides question the religious implications of making humans immortal, and thus god-like.
More practical concerns about life extension include over population. Life extension proponents point out that as life expectancy has increased, birth rate has naturally decreased. They also argue as population increases, humans become more efficient, allowing the world to sustain more inhabitants.
Ultimately, life extension won’t provide us with the answers to these questions, but it will certainly give us more time to ponder them.
References:
1) Howitz KT, et al. (2003). "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan" (PDF). Nature 425 (6954): 191–196. doi:10.1038/nature01960
2) Pearson KJ, et al. (2008). "Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span". Cell Metab 8 (2): 157–68. doi:10.1016/j.cmet.2008.06.011
3) Ellis-Behnke GH, et al. (2006). Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. PNAS 103 (13): 5054-5059. doi: 10.1073/pnas.0600559103
4) McCay CM, et al. The effect of retarded growth upon length of lifespan and upon ultimate body size. Journal of Nutrition. 1935;10:63–79.
Fontana L, et al. (2004). Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. PNAS 101 (17): 6659-6663. doi: 10.1073/pnas.0308291101