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Strategies for Engineered Negligible Senescence with Aubrey de Grey

Projects at SENS Foundation

aubrey-de-grey-stragegies-for-engineered-negligable-senescenceSens Foundation has a lot of projects that were working on all at the same time.  There are 3 projects that we are working on at our research center in California and then there are a whole bunch of others that we support at university laboratories around the world – mostly in the USA.
In the research center in Mountain View California there are 3 projects that we are working on:

  1. 1st of all, mitochondrial mutation – we’re interested in combating the accumulation of mitochondrial mutations, not actually via repairing them, but by making them harmless; by putting modified copies of the mitochondrial genes into the nuclear dna, modified in such a way that the proteins go back to the right place – even though the dna is in the wrong place. This is an idea that was actually pioneered in Australia by a group in Monash University – about 25 or 27 years ago even.  But has actually been very challenging to make work in general.  Over the last few years a number of breakthroughs have been made to make the whole thing much more realistic, and we’re perusing that with a lot of energy now.
  2. The 2nd thing we’re working on at the research center is to identify enzymes from the environment (especially from bacteria) that can break down substances whose accumulation in the body over life causes diseases like cardiovascular disease and macular degeneration. We’ve become quite good at finding enzymes that break down these substances, and now were developing ways to put them into mammalian cells in manners that actually allow the cells to survive longer.  We’ve just published in the April of 2012 the first demonstration of rescue of cells from toxic substances that accumulate in the body using a system of this nature.
  3. The 3rd thing we are doing at the research center is part of our cancer project – we’re interested in combating cancer by controlling the elongation of ends of chromosomes – these things called ‘telomeres‘ and were working specifically on a rather neglected area in that field called ALT (Alternative Lengthening of Telomeres) which is a method that about 10% of cancers use that is still very characterized genetically and we’re working on that.

Video interview here:

Medical Bioremediation

The elimination of this junk which accumulates inside cells using enzymes from bacteria is what we call medical bioremediation. We call it that because bioremediation is the use of very much the same method to eliminate pollutants from the environment as a method of environmental decontamination.
Bioremediation works extremely well; it’s not just an academic idea; it’s a thriving commercial discipline. And it certainly shows us that it’s pretty straight forward to find enzymes to break down more-or-less whateever you want so long as the thing you want to break down is organic, and rich in energy – so that the microbe can break it down and it can live off it.

The Divide & Conquer Approach to Solving Aging

Most of the work going on that is related to SENS is not directly related to longevity. And that’s because the SENS approach to combating aging is a ‘divide and conquer’ approach; an approach in which we split the problem of aging into a number of sub-problems and we address each of those individually.
In any divide an conquer approach to a complex technological problem you don’t expect to see any actual results in terms of the overall goal of the technology until all of the components are at least working reasonably well. And we’re certainly not at that stage yet. So yes, there’s masses of progress at SENS in various of the strands that we’ve been perusing – but that has not yet translated into a longevity benefit yet in any species. However there is plenty of work going on in simpler strategies to combat aging; strategies that we don’t pursue because they won’t scale – they will only give you a modest benefit postponing the diseases and disabilities of old age.
But which we’re very much happy for other people to pursue in because they may be easier to implement in human beings than the SENS approach. So, for example a few years ago it was discovered that the drug named Rapamycin was able to significantly extend the life-span of rodents – which is quite a surprise because the drug had been around a long time. But you know there have been a lot of studies of how that happens ever since that time – and we may be able to turn that into a useful therapy for human beings.
There is still a lot of excitement around drugs that emulate calorie restriction that extends lifespan of rodents especially, by tricking them (essentially) into thinking they are in a famine when they’re not. And of course there’s a lot of work going on still in trying to evaluate other approaches to combating aging by simple methods – there is always constantly new news in this area.

Will Any of the SENS Approaches Work in Isolation?

More videos about SENS can be browsed through in this playlist:

Strategies for Engineered Negligible Senescence (SENS) is the term coined by British biogerontologist Aubrey de Grey for the diverse range of regenerative medical therapies, either planned or currently in development,[1] for the periodical repair of all age-related damage to human tissue with the ultimate purpose of maintaining a state of negligible senescence in the patient, thereby postponing age-associated disease for as long as the therapies are reapplied.[2]

The term “negligible senescence” was first used in the early 1990s by professor Caleb Finch to describe organisms such as lobsters and hydras, which do not show symptoms of aging. The term “engineered negligible senescence” first appeared in print in Aubrey de Grey’s 1999 book The Mitochondrial Free Radical Theory of Aging,[3] and was later prefaced with the term “strategies” in the article Time to Talk SENS: Critiquing the Immutability of Human Aging[4] De Grey called SENS a “goal-directed rather than curiosity-driven”[5] approach to the science of aging, and “an effort to expand regenerative medicine into the territory of aging”.[6] To this end, SENS identifies seven categories of aging “damage” and a specific regenerative medical proposal for treating each.

[1]Research Themes (February 4, 2013) http://www.sens.org/research/introduction-to-sens-research

[2] de Grey, Aubrey; Rae, Michael (September 2007). Ending Aging: The Rejuvenation Breakthroughs that Could Reverse Human Aging in Our Lifetime. New York, NY: St. Martin’s Press, 416 pp. https://www.amazon.com/Ending-Aging-Rejuvenation-Breakthroughs-Lifetime/dp/0312367074

[3] de Grey, Aubrey (November 2003). The Mitochondrial Free Radical Theory of Aging. Austin, Texas: Landes Bioscience. ISBN 1-58706-155-4. http://www.sens.org/files/pdf/MiFRA-06.pdf

[4] de Grey AD, Ames BN, Andersen JK, Bartke A, Campisi J, Heward CB, McCarter RJ, Stock G (April 2002). “Time to Talk SENS: Critiquing the Immutability of Human Aging”. Annals of the New York Academy of Sciences 959: 452–62. http://www.sens.org/files/pdf/manu12.pdf

[5] Bulkes, Nyssa (March 6, 2006). “Anti-aging research breakthroughs may add up to 25 years to life”. The Northern Star. Northern Illinois University (DeKalb, USA). http://northernstar.info/city/anti-aging-research-breakthroughs-may-add-up-to-years-to/article_a4d2acd9-475d-5e12-a81c-77011f9c65ad.html http://www.worldhealth.net/news/anti-aging_research_breakthroughs_may_ad/

[6] “Age-Related Diseases: Medicine’s Final Adversary?”. Huffington Post Healthy Living. http://www.huffingtonpost.com/aubrey-de-grey-phd/age-related-diseases_b_985019.html

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