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July 17, 2009

Aubrey de Grey Interview by Sander Olson

Aubrey de Grey: Founder of Strategies for Engineered Negligible Senescence

Strategies for Engineered Negligible Senescence (SENS) is a 25-year long research strategy, currently underway, to develop a regenerative medical procedure to periodically repair all the age-related damage in the human body, thereby maintaining a youth-like state indefinitely

Question: Tell us about the SENS foundation. What is its budget? How many research projects does it currently have underway?

Answer: SENS Foundation was created in April 2009 and took over the SENS research activities of the Methuselah Foundation (MF). We have a very limited budget at this point, initially consisting of the funds that had been donated to the MF for SENS research and had not already been spent. In essence we currently have a freeze on funding anything new right now. However, we are of course working extremely hard to change that!


Question: Many of your strategies toward Strategies for Engineered Negligible Senescence (SENS) entail finding potent enzymes that degrade various molecules. How many new and useful enzymes have been discovered by the SENS foundation so far?

Answer: We've identified several enzymes that degrade each of two major "waste products" whose accumulation underlies major age-related diseases: 7-ketocholesterol, which many researchers have concluded is the most potent cause of atherosclerosis, and A2E, which has the corresponding status in respect of age-related macular degeneration.


Question: Many of the problems from ageing result from degradations in the mitochondria. Can your strategy of placing mitochondrial genes in the cell nucleus truly render the mitochondria redundant?

Answer: It certainly wouldn't render the mitochondria redundant, no - but it would render the mitochondrial DNA (mtDNA) redundant. The purpose of this therapy is to ensure that the 13 proteins encoded by the mtDNA are present in mitochondria even if the mtDNA has suffered mutations.




Question: How does SENS deal with the buildup of toxins in the body, such as heavy metals, that cannot be broken down by any enzyme?

Answer: Inorganic toxins indeed accumulate in the body, but actually there are already systems for excreting them: it's just that those systems become increasingly ineffective as a result of other changes (changes that SENS addresses directly). A good example is fat tissue. when fat is lost, heavy metals are released into the circulation - and this is actually one reason not to lose weight too rapidly. Once in the circulation, some metals are reabsorbed, but a lot is excreted.


Question: To what extent does SENS research overlap with more conventional medical research, such as gene therapy?

Answer: Well, a lot of people would hesitate to call gene therapy conventional! But SENS will certainly utilize gene therapy extensively.


Question: How much research is the SENS foundation performing on stem cells?

Answer: Basically none - and this is for a very simple reason, namely that we need to conserve our modest resources for those areas of SENS that are not being adequately pursued independently of us. Stem cell treatments will undoubtedly form a large part of the eventual SENS panel of therapies, but for the foreseeable future they'll be quite adequately advanced by others.


Question: Of the "seven deadly things" that cause ageing - cell loss, mutant mitochondria, mutations, death-resistant cells, tissue stiffening, and extracellular and intracellular aggregates - which will be the most difficult to address?

Answer: I'm in no doubt that the hardest one to address is mutations in our chromosomes. The problem with those is that they lead to cancer, which has natural selection at its disposal - so the cleverer we get, the cleverer it gets. That's why the SENS approach to combating such mutations is so aggressive, and indeed so ambitious.


Question: Is the mainstream scientific establishment becoming more receptive to your research and arguments?

Answer: Definitely. The derision that they previously met within most of the biogerontology community has become very much a minority view, as it's become more obvious that there is no scientific basis for dismissing SENS. The process has also been aided by the enthusiastic acceptance of the various SENS concepts by those whose work is most relevant to their development - researchers who are mostly not biogerontologists.



Question: What institutions currently fund your research? To what extent is your research constrained by insufficient funding?

Answer: Our research is not funded by any institutions (such as NIH), only by philanthropy. Its rate is massively constrained by insufficient funding: we could certainly spend 50 times what we currently have before we came close to running out of important projects to support.


Question: The Wyeth corporation recently unveiled a chemical called rapamune that increased mice lifespans by up to 14%. What is your assessment of rapamune's potential?

Answer: I think rapamune's potential resembles that of other interventions that have done well on mice: I don't expect them to work nearly so well in humans. That's basically because they "tune" the recipient's existing metabolism, and the selective pressure to maintain "tunability" of one's metabolic pathways is lower with longer-lived species. For humans we're going to need bona fide repair and maintenance.


Question: How has your view of ageing and SENS changed during the past decade? Are you more or are you less optimistic about SENS prospects than a decade ago?

Answer: My views have changed very little since I came up with SENS in 2000. It remains clear to me that SENS is on the right track, and my estimate of the required timeframe for its implementation (subject to funding, as always) is also little changed.



Question: How many researchers at your institute are actively involved in anti-ageing research? How many individuals are engaged in this type of research worldwide?

Answer: The answer to that question depends on your definition of "anti-aging research". Most biogerontology research is of highly questionable relevance to the postponement of aging - though of course any basic research can always stumble upon useful tricks. Conversely, lots of biomedical research that is not being done for the purpose of combating aging is in fact highly likely to contribute to eventual anti-aging therapies. With those considerations in mind, I would say that there are at least a few thousand people working in relevant areas, most of them in stem cell research.


Question: Could you tell us more about your Atherosclerosis, immunosenescence, and macular degeneration programs? How rapidly are these programs progressing?

Answer: I mentioned the atherosclerosis and macular degeneration work earlier. We're very happy about progress, as shown by the identification of these enzymes (and the publication of our results in prestigious journals), but of course there's a very long way to go. The immunosenescence program is at a much earlier stage, having begun only this past October, and it won't deliver even preliminary results for several months yet, but we're very optimistic about the project.


Question: You are currently 46. What do you consider the likelihood of your surviving to 150?

Answer: Around 50%. However, if I do, I reckon I'll have at least a 50% chance of then making it to 1000. But let's remember; that's not the object of this research. The object is to stop people getting sick, and the only thing that distinguishes SENS from other medicine for the elderly is that there's a good chance that SENS can keep people healthy so well that there will be the side-benefit of radically longer lives.
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