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article imageOp-Ed: Ending Ageing — An update from Aubrey de Grey's co-author Special

By Alexander Baron     Nov 10, 2011 in Health
Aubrey de Grey would like us all to live forever, so would Michael Rae; he took time out from a busy schedule to update us on the current state of play in gerontology.
Ageing - or aging as they say in the US, is something we all have to do, but only if we're lucky. And here to talk about it is...
MR: My name is Michael Rae; I'm one of Dr de Grey's research assistants, and coauthor of his book, Ending Aging.
The new, paperback edition has an Afterword covering some of the advances in SENS science that were made after the publication of the hardback.
AB: Before we go any further can I ask that you keep this simple for an intelligent lay readership, so no talk about Hayflick limits and the like? Can I ask what you've been up to recently? How did your Fifth Conference go, any major breakthroughs, etc?
MR: Dr de Grey has, obviously, been up to a lot. I would say that one exciting recent development is that, with an increase in our research budget this year (based on performance last year and a more optimistic financial outlook from many of our donors), we've recently approved funding for several quite important and exciting research projects. One is a project whose ultimate aim is to tissue engineer a new thymus. The thymus is a gland located near the breast bone, where T-cells (an important immune cell) mature. The thymus shrinks with age, and the tissues on the outer layer of the organ where T-cells mature lose their architectural integrity, leading to a progressive failure to produce new T-cells to fight novel infections. The thymus engineering project, which is underway with SENS Foundation support at the Wake Forest University Institute for Regenerative Medicine by Dr John Jackson and colleagues, is to use a trick that you may have heard of having been used to make a new rat heart using the tissue scaffolding of another's.
Gerontologist and Othello player extraordinaire Aubrey de Grey and two members of his team at SENS  ...
Gerontologist and Othello player extraordinaire Aubrey de Grey and two members of his team at SENS, including co-author Michael Rae.
The same trick has been used to generate a functional (although so far short-lived) set of lungs and a liver. Dr. Jackson's team will be using it to engineer a new thymus. The first studies will be done in mice, and if they succeed, they have very good access to sheep to scale the work up into a large mammal.
AB: I gather your recent 5th conference was a success?
MR: The fifth SENS Conference was, indeed, quite amazing! Unlike the previous conference, this time much more of the work being presented had already been published; it was none the less remarkable to see just how much had been accomplished in the last year, from restoring cognitive function in a mouse model of Alzheimer's disease using a drug that boosted up the ability of their brains' lysosomes ("garbage disposal systems" as it were) to break down the sticky beta-amyloid protein; to a review of Dr. Jackson's early work, and work in the gut by Dr. Graça Almeida-Porada (formerly of UN Reno, now happily saved from the financial collapse of the institution (!) by being sensibly scooped up by the more well-supported WFIRM); to a just-begun study on a very bold and ambitious way by which Dr. Jean Hébert of Albert Einstein College of Medicine proposes to restore the loss of cells and degraded circuitry of the aging neocortex (the area of the brain where, arguably, our highest, most 'human' cognitive activity occurs).
AB: This recent interview with cardiologist Dr Clyde Yancy about extending your lifespan sounds a) simplistic and b) a plea for yet more government intervention. Are you in broad agreement with it?"
MR: That depends on from what angle you look at the question. Certainly, if you don't follow his advice, you will very substantially reduce your odds of getting into your nineties and above; [there is] lots of evidence to that effect. But the magnitude of the influence he asserts is WAY out of whack with every study I've seen on the subject...genes account for only about 25% of your chances of reaching an age of about 75, they are a HUGE factor in your odds of becoming a centenarian once you have already lived that long, rather than dying shortly thereafter: at that point, it's all about basic aging, with little influence of environmental factors. But of course, if you don't reach age 75 to begin with, you can't reach 90 or 100.
That doesn't mean that taking care of yourself is worthless. Eating well and exercising will greatly reduce your odds of suffering prematurely with many age-associated disabilities and diseases (such as heart disease, diabetes, and some cancers), and because of that, lifestyle factors are major predictors of your odds of reaching what was once old age - 75 years or so - which is now actually below average. However, this has relatively little to do with aging, and a lot to do with killing yourself early with self-abuse.
AB: One of your recent postings A Green Light for the Ultimate Cure for Cancer sounds extremely optimistic. There are researchers and governments working on cancer all over the world. How is your programme different from all the others?
MR: It's actually entirely different, and that's why the study I (and it was me) reviewed in this post was so important. Other approaches to cancer are based on trying to either kill cancer cells with toxins, or to dampen down their growth or survival by targeting specific pathways they use with drugs that inhibit those pathways. And the best of these therapies (herceptin or Gleevec, for instance) do work very well in the right kind of cancer - for a while.
The problem is that cancer cells are engines of evolution due to their very rapid proliferation rates and unstable genomes, so that while a given cancer intervention may well wipe out nearly or all cancer cells, if even one survives due to a lucky mutation that allows it to adapt to this intervention, it gets to pass on its protective mutation to its descendants, multiplying as ever at a furious pace, requiring a new intervention - and so on, ad infinitum.
AB: You are taking a holistic approach then?
MR: If we're going for maintaining health indefinitely , we can't afford half measures: we need to reduce cancer risk essentially to zero. The radical solution that Dr de Grey has proposed (WILT, for Whole-body Interdiction of the Lengthening of Telomeres) appears the only way to do that, because it doesn't simply manipulate the ability of the cell to lengthen telomeres by interacting with the various elements of the telomere-lengthening machinery, but completely and irrreversibly TAKES AWAY the one thing (the ability to lengthen telomeres) that no cancer can do with out, by a mutation of the genes in that machinery. As far as I can see, nothing else (nor any cocktail or sequential protocol) will, and any such reliance on post facto intervention leaves open the risk of just not applying it properly, adequately, or on time.
You can read up on all of this (and more!) in our book, and in more formal and technical publications.
AB: [Rather than blind the lay reader with science, check out the SENS website, and one or two of their videos on YouTube].
MR: The study reviewed in Green Light... was very important, because it showed that a lot of the safety concerns that have been raised as potential deal-breakers for knocking out telomerase just don't appear to happen in the real world.
AB: A recent article in the Daily Telegraph comes down heavily on the side of Caloric restriction and supplementation for extending lifespan, but I gather your Foundation believes this is a dead end?
MR: Indeed, and unlike in the case of Caloric Restriction, where Dr de Grey is in the minority, really almost no one in the biomedical research or biogerontology fields thinks that dietary supplements are going to have any significant effect on longevity, with the exception of a very few cases of people who may have very high risk of specific diseases and for whom there is a supplement that actually does reduce risk of that disease (and there are very, very few of those).
Certainly, I don't think there's any credible case to be made that any supplement on the market actually retards the aging process, or that even very extreme CR, working as well in humans as it does in rodents, would lead to the dramatic extensions of youthful health, vigour, and longevity that can be anticipated from achieving a comprehensive platform of rejuvenation biotechnologies.
AB: Two years ago, Aubrey said your organisation had a budget of around a million dollars a year, and also that the funding of SENS research is almost entirely philanthropic. Do you have any ideas as to how this funding could be increased, and do you see any problems that could arise out of government funding, namely he who pays the piper...?
MR: On both fronts, in principle, the government is both best-endowed to dramatically expand funding and drive the overall research agenda (from dollars, but also from needed regulatory reforms, etc). And in fact, rejuvenation biotechnologies are a tune that governments should be very eager to get played. The costs of paying for keeping people with Alzheimer's, Parkinson's, and other age-related diseases are so high that it'll be cheaper for them to pay for rejuvenation therapies, not only because it will save them on health care but will also make Social Security unnecessary, reduce the frequency of road accidents, keep productive workers in their national economies, avoid the quite substantial productivity losses associated with today's "working-age" adults exiting the workforce or taking time off to care for aging parents, etc, etc.
Remember that most governments in industrialized countries actually fund the entire health care system, and even in the USA, they run Medicare which is the main health plan for nearly everyone over 65 years old.
The only sure way to get this funding source going is to ensure that their electorates will absolutely demand it. Part of that is to demonstrate the potential of actually achieving it in the face of skepticism today, which is one of the many ways that the Foundation's critical-path research can catalyze the expansion of the overall financial and intellectual capital pool being directed toward rejuvenation biotechnology. Another is to spark the same realization in the biotech industry.
AB: Finally, what have you got lined up for the longer term?
MR: More of the same, just on a bigger scale, in more directions, etc, until the momentum of government and industry research on rejuvenation biotech is self-driving and expanded into all of the necessary planks within the overall rejuvenation biotechnology platform.
This opinion article was written by an independent writer. The opinions and views expressed herein are those of the author and are not necessarily intended to reflect those of
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