What is Robust Mouse Rejuvenation, and Why Should We Care?
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SENS, the Strategies for Engineered Negligible Senescence is a detailed research plan for developing the means to prevent and reverse degenerative aging by repairing its causes. SENS assembles the list of causes from the present scientific consensus on fundamental differences between old and young tissues, differences that are not known to be caused by any lower-level process. The potential repair therapies are also assembled from the best and latest of research strategies in a range of fields: stem cell therapies, targeted cell destruction, engineered enzymes to break down unwanted biomolecules, immune therapies, and so forth. SENS as a program is shepherded by the SENS Research Foundation but has growing support in the broader scientific community, and far from every last relevant research program is actually initiated by, funded by, or even known to the Foundation.

Robust mouse rejuvenation (RMR) has been the first long term milestone for SENS since its proposal and initial development by Aubrey de Grey. No new technology arrives fully formed, and it is understood that the first versions will be flaky, expensive, and generally much less effective than the later refinements. But in the case of rejuvenation treatments, this may not matter all that much, as even a somewhat effective form of rejuvenation provides the patient more time in which to wait on those refinements - or perhaps even assist in their development. So robust mouse rejuvenation as originally outlined means a full enough implementation of SENS to be capable of doubling the remaining life expectancy of an elderly mouse, demonstrated and then replicated in rigorous laboratory studies. It doesn't mean an absolutely complete implementation, and it doesn't mean full and absolute rejuvenation: it is a first pass to demonstrate greater benefits than any other approach to date.

It is important to note that when I talk about implementation of SENS in the laboratory, I am almost always talking about robust mouse rejuvenation. I do not mean clinical translation of this result, and neither do I mean a complete and fully effective suite of rejuvenation treatments. The path from robust mouse rejuvenation to the clinic might be decades long in the highly regulated US and Europe, but first generation SENS treatments will hopefully jump into clinics in other parts of the world just as rapidly as did first generation stem cell therapies. Medical tourism is a wonderful thing, and will probably one day save your life.

SENS is presently divided into seven general categories of damage that cause aging, each of which seems largely independent from one another and requires a very different approach to repair: a whole different line of research, no doubt running in different labs and organized by different research groups. We may see the seven categories split further in the years ahead if any of the subcategories prove to be either much harder or more important to aging than is presently assumed. For example, if I were writing SENS from scratch I might put immune system aging in its own bucket rather than lumping it under the general category of death-resistant cells. But that's just my view.

It is presently thought that each category of age-related damage in SENS is enough to kill you in roughly a human life span or a little longer even if all of the others are defeated. This may or many not turn out to be the case, but the evidence for this viewpoint is compelling, as each of the SENS categories of damage has at least one fatal age-related condition associated with it, and for which it is the primary known driver. This is in fact how these forms of damage were first categorized and investigated by the research community, as researchers work backwards from the visible and deadly consequences of aging in search of the mechanisms by which they unfold. The assumption that all aspects of SENS must be at least partially addressed in order to prevent aging and extend healthy life is why robust mouse rejuvenation is marked as a goal: get every category of repair treatment in the SENS portfolio working to at least the level of a proof of concept.

How long remains between now and the implementation of robust mouse rejuvenation? Ah well, there's the rub. How long is a piece of string? It is very hard to predict timelines for research when funding is at a low ebb, even research like SENS wherein it is fairly clear as to what the researchers should be working on, which lines of work are most promising, and where the end goals lie. If there was a good level of funding for SENS, say at the level of $100 million a year, then we could fall back to planning estimates of a decade or so to get to robust mouse regeneration. We could do that because with that much money there can be many irons in the fire, and the law of averages begins to smooth out random chance: some projects fail, some do very well and come in early, surprise advances sometimes happen, and some projects take far longer than they were expected to. When there is comparatively little funding then progress in research is uncertain, and I would be surprised to learn that there was more than about $10 million devoted to directly SENS-related work outside the stem cell and cancer research communities this year given that the SENS Research Foundation's yearly budget is around $5 million at the moment.

The glass half full way of looking at this is to see that people like you and I can make a large difference to the level of funding just through ordinary fundraisers, like those that raised $20,000 and $60,000 for SENS research projects last year.

But I think it is worth bearing in mind that robust mouse rejuvenation is not a coordinated single point in time at which all parts of SENS will suddenly become available at once. Different areas of SENS research stand at very different stages of readiness and progress, and some will clearly be done first, and perhaps considerably in advance of the others. The best candidates at this point for early success are, I think, breaking of glucosepane cross-links and mitochondrial repair of some form. If a method of breaking down the predominant form of cross-links in human tissues is demonstrated to produce benefits, will the world sit around waiting for robust mouse rejuvenation in order to develop it? Of course not. In fact, I'd wager that robust mouse rejuvenation will probably be contemporary with medical tourism for first generation treatments based on the more easily developed parts of the SENS rejuvenation toolkit.

You may still get nailed by one of the other forms of age-related damage on roughly the same time scale as a normal human life span, but it is hard to argue that you will not find improvements to health and function through repair of only one or two forms of age-related damage. If you can undergo a treatment to remove glucosepane cross-links to improve function of skin and blood vessels, then I'd argue that your life is better as a result even though all of the other forms of damage are gnawing away at your health in their own ways. Robust mouse rejuvenation is an aspirational goal, but it isn't a dividing line. Results will be more piecemeal and staggered, and any result with significant merit will probably be rapidly developed as a treatment in less regulated parts of the world. Until research funding for SENS and SENS-like research grows greatly, the pace of progress towards rejuvenation will remain variable and uncertain.

Comments

Yes hopefully some breakthroughs in the breaking of glucosepane cross-links or mitochondrial repair will unlock more funding and support.

I don't know if it is just wishful thinking, but I think with these fields there might be a tipping point... or there might not.

I wonder whether a treatment to remove glucosepane cross links would make people's skin look younger? If that is the case then any working therapy would probably be rapidly translated to the clinic.

Posted by: Jim at April 16, 2014 6:04 AM

http://www.quora.com/Longevity-and-Life-Extension/How-close-are-we-to-decoding-the-aging-process-and-living-for-either-a-very-long-period-of-time-or-indefinitely

I think Dr. De Grey intentionally stopped making predictions in his talks. However, last July he said:

"I think the critical-path work required during the next 6-8 years needs about $50M per year before hitting diminishing returns, i.e. being limited by the scientific challenges more than by budget. With that budget, I think it'd take about that long to reach the milestone I've termed "robust mouse rejuvenation", i.e. extending the healthy lifespan of normal mice by two years with interventions begun when they were already in middle age. It's about 10x more than the current budget of SENS Research Foundation, which is the only organisation doing most of that critical-path work. If we had to continue at the current level of funding, I think we'd take at least five years longer to reach RMR."

BTW good stuff in his Quora. Too bad he doesn't extend the same openness and partcipation to twitter and fb.

Posted by: johnathan at April 16, 2014 4:54 PM
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