Sifting the Epigenetic Sea in Search of Sense and Meaning
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The SENS Research Foundation (SRF) has enough of a budget these days to be funding a fair number of distinct research projects relevant to aging and longevity - too many for me to be familiar with all of them at this point. Some are fairly indirect, fundamental research that aims to build the foundations needed to even start in on projects that cut to the heart of the matter, the construction of rejuvenation biotechnologies that can reverse the course of degenerative aging. Bear in mind that as research progresses, it will not be the Foundation that funds or accomplishes the bulk of the work needed to make human rejuvenation a reality: these are still the early days, and it is as important to provide groundwork that opens the doors for other groups, or makes a field more financially attractive for development, as it is to make direct headway.

One of the Foundation's areas of interest is cancer and its causes, and this is where you'll find a lot of the more indirect work. There is a broad outline in WILT - whole body interdiction of lengthening of telomeres - as a path to build the ultimate cure for cancer, but it is also the case that a large amount of fundamental genetic science and tool-building is needed to validate and make progress on that path. For my money, I see cancer research as being in much the same state as stem cell research, by which I mean that a massive research edifice is already heading in roughly the right direction, making fair progress towards therapies that a few decades from now will be good enough to get by for the foreseeable future. Stem cells and cancer treatments are not presently set to be the limiting factors for the future of treating and reversing aging, in my opinion.

I'm not running the SRF, of course, and if you look over the Foundation's annual reports you'll see quite a lot of interest in specific tool-building at the intersection of genetics and cancer to arrive at more radical solutions for cancer than those pursued by the present mainstream. (The next generation of cancer therapies emerging from that mainstream are based on selective targeting of cancer cells, offering the promise of few side-effects and high effectiveness - which sounds pretty good to me). You can read an introduction to this area of work at the SENS website, and note that it may well also overlap with means of generating data relevant to questions on aging that are of greater interest than rejuvenation to the research mainstream, such as whether there is any merit at all in programmed aging theories, or whether there are any significant and widespread genetic contributions to longevity in humans.

One area of interest here is the generation and analysis of epigenetic data, something that I'm generally not so hot on as a point of relevance to human longevity, given its usual association with the development of drugs to slow aging or other ways to manipulate metabolism without addressing the underlying causes of dysfunction. Those are the slow roads, unlikely to produce great gains in healthy life span. But here is a piece by philanthropist Jason Hope on the way in which one SRF-funded research program is using epigenetic tools to arrive at a potentially better grasp on cancer at the opening stage, in its very earliest development:

Epimutations  -  Identifying Changes in Structures Controlling the Genetic Code

With funding from SENS Research Foundation, Albert Einstein College of Medicine (AECOM) Team members Dr. Vijg and Dr. Gravina have developed novel ways of identifying changes in the "scaffolding" that structures and controls the expression of the genetic code. These innovative approaches also help scientists determine if these changes in DNA are a response to environmental exposure or the result of damage to the scaffolding, leading to accumulating errors in the regulation of the DNA code. These methods may someday change the way doctors diagnose illnesses, such as cancer, and slow or reverse some of the debilitating effects of aging.

Dr. Gravina and the team tested the new evaluation method by analyzing DNA methylation in thousands of single liver cells, each from a different mouse. The researchers looked at specific locations in DNA scaffolding that control whether the genes are methylated or demethylated. This approach allowed scientists to compare the distinctive methylation and demethylation of individual cells with the widespread patterns of methylation occurring in a larger scale throughout the entire liver.

In other words, Dr. Gravina and his team found a way to determine whether changes in methylation were responses to environmental conditions common to many cells in the liver or were aberrant patterns unique to individual cells  -  widespread changes are likely the response to environmental stimuli whereas single cell deviations from the wider pattern are likely to be the result of damage to the epigenetic structure. The new approach developed with the support of SENS Research Foundation funding could be the foundation for new technologies for identifying cancers at their earliest stages.

You can probably see how this work will be of interest to researchers studying genetics and longevity, especially those who think that aging is a programmed set of epigenetic changes. As to cancer: the advantage of very early detection of cancer is that we don't need radical new technologies to eliminate early cancers with a high degree of reliability and comparatively little trauma. That goal is achievable with incremental advances in medical technology in the near term. Getting rid of very early stage cancer is very possible for many cancers even today, but the trouble is that by the time cancer is discovered it is almost always well past that stage. So there is a path here towards making the mainstream initiatives in targeted cancer treatment far, far more effective than would otherwise be the case. But again, I see this all happening on a good schedule with or without the help of the SRF: work on early detection of cancer is already an established line of research. This thus looks like tool-building, a process of making technologies that are needed for other Foundation work, and which also happen to have much broader applications in mainstream medicine.


I think the foundation's interest in this is to guarantee that SENS covers all the causes of aging that need to be addressed. Epigenetic noise has been proposed as an (additional) independent root cause of aging. This research promises to resolve the question whether it is or not.

If epi-mutations do cause aging, that makes the job of achieving robust rejuvenation harder, though not impossible. The brain would be the most problematic location for these damaging epi-mutations. If they contribute to aging of other organs than the brain, I would think the impact on SENS could be minor, but if they contribute strongly to brain aging then novel techniques will be required. There is a talk titled "What good is an old brain in a young body -- a strategy for regenerating the neocortex" by Jean Hébert on the SRF youtube page. This talk perhaps gives a hint toward a technique that could rejuvenate the brain regardless of epi-mutations (if they are a problem).

Posted by: José at March 12, 2014 4:25 AM
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