Los Angeles, California—If you’re under age 30, it is likely that you will be able to live as long as you want. That is, barring accidents and wars, you have centuries of healthy life ahead of you. So the participants in the Longevity Summit convened in Manhattan Beach, California, contend. Over the weekend Maximum Life Foundation president David Kekich gathered a group of scientists, entrepreneurs, and visionaries to meet for three days with the goal of developing a scientific and business strategy to make extreme human life extension a real possibility within a couple of decades. Kekich dubbed the effort the Manhattan Beach Project.
Tech entrepreneur and futurist Ray Kurzweil opened the conference with a virtual presentation on exponential technology trends that are bringing the prospect of achieving longevity escape velocity ever closer. “We are very close to the tipping point in human longevity,” asserted Kurzweil to the conferees. “We are about 15 years away from adding more than one year of longevity per year to remaining life expectancy.” This has been labeled by summiteer and life-extension guru Aubrey de Grey as longevity escape velocity. Achieving escape velocity, according to Kekich, would mean that “your projected day of reckoning moves further away from you rather than closing in on you.”
“Health and medicine will be a million times more powerful in 20 years,” Kurzweil declared. He predicted that the complexity of biology will yield to the exponential powers of applied information technology and take off. He cited Moore’s Law which predicts doubling of microchip functionality and halving their costs every two years. The decrease in cost and increase in speed of sequencing whole human genomes is outpacing even Moore’s Law. In 2000, the first genome was sequenced after 14 years and at a cost of $3 billion. Now various startups offer the potential to sequence an individual’s DNA for less than $100 in under an hour.
The goal of the summit was to devise scientific and business strategies with the goal of demonstrating the capability to reverse aging in an older human being by 2029. By then, Kurzweil argued, people will be beginning their intimate merger with information technologies, biotechnologies, and nanotechnologies. Kurzweil, age 61, emphasized, “Something I am personally interested in is not just designer babies, but designer baby boomers.”
Going Back to Move Forward
Anti-aging research is a rich and varied territory right now. Researchers are finally beginning to get a handle on the actual causes of aging. With this increased scientific understanding, some researchers now believe they are on the way to figuring out how to stop it, and—eventually—how to reverse it.
University of California, Riverside biochemist Stephen Spindler reported on his research seeking caloric restriction mimetics. It is well established that restricting many mammal species to about two-thirds of what they would ordinarily eat extends their healthy lifespans. For example, calorie restricted mice live up to 50 percent longer, and experience less heart disease and cancer than those who eat as much as they want. Spindler is now screening a variety of compounds including pharmaceuticals to see if they mimic the effects of calorie restriction in mice. He presented early results that show that some compounds, like cholesterol lowering statin drugs and the immune suppressant rapamycin, do seem to increase mouse lifespans. However, Spindler added that more is not necessarily better. Mice receiving combinations of compounds are not living any longer. “I personally would caution people taking large amounts of supplements in combination to be careful,” said Spindler. The good news is that several major pharmaceutical companies are working on calorie restriction mimetics known as sirtuins.
Michael Rose, a biologist at the University of California, Irvine, has been breeding long-lived fruit flies to one another for decades. Rose’s work is built on the premise that natural selection is the cause of aging. Specifically, natural selection works to keep organisms healthy and alive until after they have reproduced. Once they’ve reproduced, natural selection no longer works to prevent the accumulation of damage that leads to aging and death. Your body is no longer needed by your germ cells once their genes have moved on to the bodies of your children.
Using artificial selection for longevity, Rose has produced fruit flies that live four times longer than normal, the human equivalent of being healthy at age 300. The Methuselah flies are more fecund and better at handling environmental stresses than are normal flies. Since fruit flies and humans share many similar genes, insights garnered from the genomics of long-lived flies are being used by Genescient LLC to develop anti-aging supplements for people. The company plans to release its first product in 2010. “In my world biological immortality is possible,” said Rose.
William Andrews, head of Sierra Sciences (motto “Cure Aging or Die Trying”) talked about his company’s project to identify compounds that lengthen telomeres. Why do that? Telomeres are repeated sequences of DNA that cap the ends of chromosomes to keep them from unraveling and to keep them from binding to other chromosomes. At conception, telomeres are about 15,000 repeats long. Each time a cell divides it loses about 100 repeats, growing ever shorter. When the repeats get short enough, cells generally receive a signal that tells them to die. Andrews argues that telomeres control aging in cells and thus control aging in us. A new study this month reports that centenarians have longer telomeres than controls do.
According to Andrews, when an adult’s telomeres get down to about 5,000 repeats they die of old age. By looking at telomere length in a blood sample, Andrews claimed, “I can tell how old you are and how long you have before you die of old age.” (For the curious, Spectracell offers a commercial telomere length test.) The only cells in our bodies that do not suffer telomere shortening are reproductive cells because the enzyme telomerase keeps adding new repeats as they divide. The goal of Sierra Sciences is to develop compounds that will reactivate telomerase in somatic cells to stop telomere shortening. After screening more than 160,000 compounds, Sierra has come up with 33 that activate telomerase and lengthen telomeres. “This would be the biggest thing to hit the planet, if we can turn these into drugs,’ said Andrews. Also represented at the summit was TA Sciences which manufactures a telomerase activator as a supplement called TA 65, which is derived from the astragalus plant. Cost? A mere $8,000 for a six month supply.
Why do some people live to be over 100 years old? That’s the question that Stephen Coles, head of the Supercentenarian Research Foundation (SRF) is trying to answer. Supercentenarians are people who are over 110 years old. In the world there are 76 currently validated supercentenarians, 72 are female and 4 are male. The genetic underpinnings of their longer lives are still murky. However, Coles has performed a number of autopsies and he has found that most died of senile cardiac amyloidosis, the accumulation of amyloid fibers in their heart muscles.
John Furber, founder of Legendary Pharmaceuticals, discussed the problem of accumulating crosslinked proteins and sugars inside and outside of cells, e.g., fibers like those that killed Coles' supercentenarians. The digestive organelles inside cells called lysosomes slowly become clogged with advanced glycation end-products (AGEs). The promise of one product that aimed to break up damaging crosslinks, alagebrium, has faded with the financial prospects of the company that developed it. If old fibroblasts, the cells that produce connective fibers, could be rejuvenated, say by restoring their telomere lengths, then, perhaps drug interventions like alagebrium might not be needed. Interestingly, there is some evidence that periodic fasting upregulates autophagy, the process by which cells digest accumulating cellular and extracellular junk.
Anti-aging research is not for the faint-hearted. Biologist Michael West was one of the founders of the biotech stem cell company Geron. He later founded Advanced Cell Technology which worked on therapeutic cloning. Therapeutic cloning, a.k.a somatic cell nuclear transfer, involves inserting nuclei from specific patients into human eggs to produce stem cells that are immunologically matched to those patients. The goal would be to transform these stem cells into other cells—nerve, muscle, immune system cells—which could be used to repair damaged or old tissues and organs.
That’s the theory, but no one has been able to perfect the practice; no stem cell lines have been derived from cloned human embryos so far. West now heads up BioTime, which is increasingly focused on using induced pluripotent stem cells (IPS cells). IPS cells are created by dosing normal adult cells, say skin cells, taken from a patient with various embryonic factors that cause it to revert to an earlier stage of development. IPS cells can be transformed into other types of cells which can be used to repair damage or rejuvenate tissues and organs. For example, new hemangioblasts, the precursor cells of blood, could be used to reconstitute and rejuvenate the human immune system.
Former biotech company founder Robert Bradbury proposed that the accumulation of misrepaired double strand breaks in the DNA that makes up our genes as a significant cause of aging. If a single strand is broken, the second strand functions as a template for guiding the proper repair of the broken one. Misrepaired genes make distorted proteins which do not work as well or not at all. By age 70, each cell averages several thousand double strand breaks. However, some cells are unscathed by these breaks. Bradbury is developing techniques to identify these “pristine stem cells” which he believes may be used to grow new organs and tissues to replace damaged or old ones. He points out that there are some 2,600 stem cell therapy trials currently underway in the U.S.
Gregory Fahy, the chief scientific officer of 21st Century Medicine is working on the cryopreservation of tissues and organs. Fahy pointed out that about one-third of people die of organ failure, e.g., heart attacks, kidney failure, and the like. The problem is that the ice crystals that form during freezing damage organs a lot. His company has developed a number of low toxicity cryoprotectants which enable the vitrification of organs as they cool. Vitrification prevents the formation of ice crystals and thus limits freeze damage. Vitrified corneal cells transplanted into the eyes of vervet monkeys work. Fahy has successfully transplanted a dog kidney kept at 0 degrees Celsius for four days.
Theoretical biogerontologist, Aubrey de Grey, the founder of the SENS Foundation and the Methuselah Foundation, is the energizer bunny of anti-aging scientific research and advocacy. SENS stands for Strategies for Engineered Negligible Senescence, which De Grey defines as “an integrated set of medical techniques designed to restore youthful molecular and cellular structure to aged tissues and organs.” De Grey focused on one proposed anti-aging solution which is to install mitochondrial genes in the nuclei of cells. One theory of aging is that the cellular powerhouses, the mitochondria, produce highly reactive molecules called free radicals as a side effect of generating energy to run cells. These free radicals over time cause mutations in mitochondrial genes which become ever more damaged, producing even more free radicals in a downward death spiral. If these mitochondrial genes could be moved to the more protected nucleus this free radical death spiral could be greatly attenuated. Engineering this migration from mitochondria to nucleus has been successful for one gene so far.