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. eat survive reproduce cartoonSpecifically, 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.
telomeresAccording 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 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.
De Grey also addressed the problem of eliminating the damaging crosslinked proteins and sugars that clog cells and damage the extracellular matrix. The SENS Foundation is funding research to find enzymes in bacteria that degrade these organic complexes with the goal of turning them into drugs.
Beyond Biology
One major barrier to cracking the problem of aging is a shortage of researchers. Computer scientist Peter Voss, the founder of Adaptive Artificial Intelligence, aims to solve that researcher shortage by creating the equivalent of thousands of researchers and research assistants by means of artificial general intelligence. “Imagine hundreds of thousands of Ph.D.-level machines chipping away at the aging problem,” mused Voss. Two years ago at the Singularity Summit, Voss declared, "In my opinion AIs will be developed almost certainly in less than 10 years and quite likely in less than five years." At the Longevity Summit, Voss predicted that his artificially intelligent researchers would be ready in six years.
Biology is nanotechnology that works. Robert Freitas and Ralph Merkle, from the Institute for Molecular Manufacturing, outlined their vision of how a robust medical non-biological nanotechnology would work in 20 years or so. Freitas won the 2009 Feynman Prize for Theory, in recognition of his pioneering work in molecular mechanosynthesis. Nanotechnology aims to control matter at the atomic and molecular scale. “The difference between good and bad health is how your atoms are arranged,” pronounced Merkle. respirocyteThe goal of medical nanotechnology is to unleash exceedingly tiny machines to patrol throughout the body and its cells repairing damage as it occurs. They envision respirocytes to carry oxygen more efficiently than red blood cells; microbivores to attack and digest pathogens; and even chromallocytes to repair and replace damaged chromosomes.
In his presentation Kurzweil envisioned constant nanotech monitoring of individual brain cells. Such nanotech devices would “ultimately capture our mind files and back them up,” suggested Kurzweil. “A thousand years from now, people will think it pretty daunting the people today went through life without backing up their mind files every day.”
But what if you don’t live long enough to take advantage of the new longevity treatments coming along in a couple of decades? For example, this life expectancy calculator suggests that there is a 50 percent chance that I will live only another 33 years. Kekich, who convened the summit, urged participants to take good care of their health—diet, exercise, supplements, stress management—because they are not gambling on just 15 years more of life, but perhaps 1,500 years of life.
Alcor DewarBut what if the grim reaper comes despite your best efforts to stave him off? Ralph Merkle, in his role as a board member of the Alcor Life Extension Foundation, explained the goal of cryonics. Cryonics involves storing human bodies or brains at the temperature of liquid nitrogen (320 degrees below zero Fahrenheit). Alcor defines cryonics as “a speculative life support technology that seeks to preserve human life in a state that will be viable and treatable by future medicine.” Or as Merkle put it, “We want a second opinion from a future physician.” The idea is that if brain structure is preserved, nanomedical devices would be able to restore a person to life sometime in the future. Merkle acknowledges that cryonics is highly experimental (to say the least), but we do also know what happens to the control group. Merkle ended with his standard quip, “So you have to decide if you want to be in the experimental group or the control group.”
Immortality, Inc.
Some the brainstormers in the business strategy session of the Manhattan Beach Project were new media entrepreneur and Disney executive Oliver Luckett, 2008 Libertarian Party VP candidate Wayne Allyn Root, computer and biotech entrepreneur Richard Offerdahl, marketing expert John Lustyan, social media marketer Michael Terpin, Lifestar Institute COO Kevin Perrott, CEO of TA Sciences Noel Patton, filmmaker Michael Potter, marketer Joe Sugarman, computer entrepreneur Ken Weiss, and Bill Faloon, co-founder of the Life Extension Foundation.
Hanging over the entire event was a single question: Why are so many people unaware of the tantalizing possibility of soon achieving extreme human life extension? And why do so many reject it when they hear about it? Luckett put his finger exactly on the chief problem. Aspiring to live for hundreds of years sounds creepy to most people. And the longevity “space” is filled nearly to the brim with scammers and charlatans, peddling all manner of 21st century snake oils.
To illustrate the creep-out factor, Luckett told the story of offering the trailer to the documentary about Ray Kurzweil, Transcendent Man, to run on his father’s campaign website (his father is running for governor of Mississippi). The campaign handlers took one look at it and said, “Keep that trailer as far away as possible. We can’t have a trailer talking about transcending religion being shown at the local Baptist church.”
As someone who has leveraged social media into several businesses, Luckett urged summiteers to focus their efforts on spreading their message using those new communications technologies. People trust new ideas that come from their friends. Of course, social media “friends” now include stars and athletes. Being in Tinsel Town, the assembled marketers spent some time brainstorming about which film or TV stars might take up the cause of promoting longevity research. Apparently, Suzanne Summers is an enthusiast, but I sure hope that the summiteers can find some other celebrities.
The summiteers also puzzled over the frustrating fact that no billionaire evidently wants to live forever. Why else have none come forward to finance serious life extension research? Entrepreneur Offerdahl explained that rich people fear the ridicule of their friends. Longevity quackery is rife and rich folks don’t want to suffer embarrassment in front their friends who would accuse them of being dupes. Like all non-profit efforts, the summiteers longed to find one billionaire who would risk ridicule to support serious life extension research.
How much cash is needed to get a good start on the goal of stopping aging by 2024 and demonstrating that it can be reversed by 2029? Kekich crunched numbers to come with a figure of a mere $63 million to jump start a future of perpetual youth. Of course some avenues are already being explored by well-funded biotech and pharmaceutical companies, e.g. calorie restriction mimetics like sirtuins. After batting around a few ideas, the group finally focused on a proposal by Bill Faloon to create a public life extension research company. The goal of the corporation would be raise money to invest specifically in companies that research technologies aiming to stop and reverse aging, not just treat diseases. The Manhattan Beach Project participants would seek to raise an initial $5 million before bringing the company to the public. Faloon and another participant committed a million dollars to the project. One idea was to call it MaxLife Capital, but my favorite proposed corporate moniker was Immortality, Inc.
At the end of the summit, David Kekich’s poignant question still resonates: “Will you be part of the last generation to die from aging, or will you be part the first generation to enjoy open-ended youth and vitality?”
Ronald Bailey is Reason's science correspondent. His book Liberation Biology: The Scientific and Moral Case for the Biotech Revolution is available from Prometheus Books.
Micro Sez:
Awesome. Anybody here know more about this Genescient?
