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Introducing the Longevity Research Institute

by sarahconstantin
8th May 2018
Otium
1 min read
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54

Introducing the Longevity Research Institute
8Gordon Seidoh Worley
13sarahconstantin
3ChristianKl
4Raemon
3sarahconstantin
2ChristianKl
2sarahconstantin
12Vaniver
2TheWakalix
8Vaniver
3ESRogs
4Vaniver
6johnswentworth
9ESRogs
5ESRogs
2ChristianKl
2sarahconstantin
0Elizabeth
4Matt Goldenberg
5Elizabeth
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[-]Gordon Seidoh Worley7y80

How, if at all, do you see LRI comparing to SENS Research Foundation?

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[-]sarahconstantin7y130

Vaniver is right.

The mainstream biogerontology perspective is that there's an evolutionarily conserved "survival program", probably developed for surviving famines, that can slow the aging process somewhat. This is the stuff you'll find in Cynthia Kenyon's research, for instance. The hope is that you can find drugs that stimulate these pathways, and thereby slow down the incidence of age-related diseases. This is the approach LRI is taking.

The SENS position, as I understand, is that this won't work. As you go up from yeast to nematodes to flies to mice, "long-lived" mutants live less long, and perhaps by the time we get to humans these genetic alterations (or drugs that simulate them) won't be long-lived at all. SENS instead wants to work on reversing the damage caused by aging.

I don't know with high confidence whether SENS's skepticism is right; but even if they are, their research program seems to involve a lot of open questions in basic science that would take a long time to resolve.

Give to SENS if you want to invest in basic research that might one day reverse aging altogether; give to LRI to accelerate translational research into treatments that might lead to modest healthspan extension in the next decade or two. (Or give to both!) They're complementary strategies.

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[-]ChristianKl7y30

As far as I understood SENS position, it's: Approaches like getting a few substances that act on a few pathways might add a few years of life but they won't provide long-term immortality.

Do you think it's different and that you actually have different assumptions about the amount of life-years that can be gained by a few of the substances that you might test?

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[-]Raemon7y40

Don't know what Sarah's take is, but I can easily see a position like "if you want to keep as many people alive as are currently alive, you want both long-term immortality getting researched, and short-term immortality getting researched (esp if the latter is easier), to keep more people around until the longterm immortality"

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[-]sarahconstantin7y30

Yep, that is my position.

(I've talked a bunch with Aubrey de Grey and he is very much supportive of the LRI's program. We're complements, not substitutes.)

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[-]ChristianKl7y20

Sarah wrote "The SENS position, as I understand, is that this won't work." and sounds to me like the disagreement isn't just about short-term and long-term solutions where it makes sense to fund both.

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[-]sarahconstantin7y20

I'm a little more optimistic about calorie restriction mimetics than Aubrey, but I think everybody sensible has pretty low confidence about this.

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[-]Vaniver7y120

I asked Sarah this a while ago, and her answer (as I recall it) was that SENS is targeting more basic science stuff that's on the left side of the 'valley of death,' and so is orthogonal (and complementary to) the sort of work LRI is doing, and will also likely take longer to result in treatments in humans.

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[-]TheWakalix7y20

By the way, what is this "valley of death"? Googling only turns up information about Death Valley and the Bible quote, and refinement to "longevity research" just leads to this valley where people supposedly live longer. It seems like an interesting concept.

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[-]Vaniver7y80

The "valley of death" in scientific contexts is research that is not profitable to do that is in between research that is profitable to do (and thus is where good ideas go to die). In this particular context, it's feasible to do preliminary studies of whether or not drugs will help with particular biomarkers of aging in old mice, and it's feasible to do final studies of whether or not drugs are safe and effective in humans, but it's not profitable to give those drugs to mice as they age and see how long they live (because you can't immediately turn that into a drug, and everyone will know if it works, so it doesn't advantage you relative to other companies, and it's the sort of thing that normal grantmakers won't fund academics to do).

Hence, nonprofit work to do the science that everyone wishes someone else would pay for.

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[-]ESRogs7y30

Was "left side" an arbitrary choice in your comment above, or is there a conventional meaning to left vs right for this valley of death?

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[-]Vaniver7y40

Arbitrary, inspired by reading left to right.

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[-]johnswentworth7y60

Donated. I've been wanting to see something like this for a while, excited to see it happen.

I'm sure there's a dozen people reading this and preparing their argument for why it probably won't work, but remember: with this kind of upside it's worth donating even for a small chance that it will work. I wouldn't give it very high chance of success, maybe 10-20% of proving something which increases human lifespan by at least 15 years, but that's a very worthwhile investment.

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[-]ESRogs7y90
I wouldn't give it very high chance of success, maybe 10-20% of proving something which increases human lifespan by at least 15 years

Those numbers sound not just very high, but practically stratospheric! Seems like it could have orders of magnitude worse odds than that and still be a great donation target.

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[-]ESRogs7y50

Just donated as well. Eager to hear more.

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[-]ChristianKl7y20

What's the point in testing them individually? Why not simply do a multivariate test with all 50 compounds?

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[-]sarahconstantin7y20

Practical constraints. The main contributor to the cost of a lifespan study is the cost of upkeep for the mice -- so it's proportional to number of mice and length of the study. Testing 50 compounds at once means raising 50x the money at once (which is out of reach at the moment) and may also run into constraints of the capacity of labs/CROs.

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[-]Elizabeth7y00

Moved to front page

Full disclosure: I'm on the board of LRI.

EDIT: I misinterpreted the policy and promoted this to front page when I shouldn't have.

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[-]Matt Goldenberg7y40

The announcement post for RAISE was specifically removed from the front page, with Oliver stating the reason was that there was an explicit LW policy to not allow organization announcements on the front page. Can we perhaps get some clarity on this policy?

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[-]Elizabeth7y50

This was my bad- I misinterpreted a conversation and thought these were okay for the front page. You're correct on the policy, thanks for pointing it out.

Reply
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I’ve just founded a nonprofit, the Longevity Research Institute — you can check it out here.

The basic premise is: we know there are more than 50 compounds that have been reported to extend healthy lifespan in mammals, but most of these have never been tested independently, and in many cases the experimental methodology is poor.

In other words, there seems to be a lot of low-hanging fruit in aging.  There are many long-lived mutant strains of mice (and invertebrates), there are many candidate anti-aging drugs, but very few of these drugs have actually been tested rigorously.

Why?  It’s an incentives problem.  Lifespan studies for mice take 2-4 years, which don’t play well with the fast pace of publication that academics want; and the FDA doesn’t consider aging a disease, so testing lifespan isn’t on biotech companies’ critical path to getting a drug approved.  Mammalian lifespan studies are an underfunded area — which is where we come in.

We write grants to academic researchers and commission studies from contract research organizations.  Our first planned studies are on epitalon (a peptide derived from the pineal gland, which has been reported to extend life in mice, rats, and humans, but only in Russian studies) and C3 carboxyfullerene (yes, a modified buckyball, which prevents Parkinsonism in primate models and has been reported to extend life in mice).  I’m also working on a paper with Vium about some of their long-lived mice, and a quantitative network analysis of aging regulatory pathways that might turn up some drug targets.

We’re currently fundraising, so if this sounds interesting, please consider donating. The more studies that can be launched in parallel, the sooner we can get results.