The Prospect of Filtering Harmful Factors from Old Blood

The Life Extension Advocacy Foundation volunteers here interview Irina and Michael Conboy, two of the more influential scientists involved in parabiosis research. When the circulatory systems of an old mouse and a young mouse are connected, the older partner shows some reversal of measures of degenerative aging, while the younger partner shows some acceleration of similar measures of degenerative aging. The Conboys have of late produced evidence to show that this is based on the presence of harmful factors in old blood, where parabiosis dilutes harmful factors in the old mouse but also passes them over to the young mouse. There is similar evidence for beneficial factors in young blood passing in the opposite direction, however.

All of this data raises the possibility of somehow filtering out the harmful factors if they can be reliably identified. While numerous forms of blood filtration equipment exist today, it seems unlikely to me that being hooked up to a suitably adapted variant for a short time would provide lasting benefits - though it could certainly be used in studies to settle debates over the degree to which specific factors are involved or important. Harmful factors are, after all, generated on an ongoing basis by cells that are damaged or are reacting to the damage of aging. To produce useful results, filtering would have to be permanently in place, such as via an implant of some sort, or enhancement to the kidneys, or pharmaceuticals that inhibit harmful factors, and none of these options seem likely to appear immediately - all would require significant development. Even with that development, such an approach is not actually addressing the causes of the issue, but rather tries to patch over just a thin portion of it.

For the sake of those new to the topic, what is it in young blood and aged blood that affects aging?

Numerous changes in the levels of proteins that together regulate cell and tissue metabolism throughout the body. We wondered why almost every tissue and organ in the body age together and at a similar rate, and from the parabiosis and blood exchange work now think that young blood has several positive factors, and old blood accumulates several negative, "pro-aging" factors. We have published on improved liver regeneration, reduced fibrosis and adiposity by transfusion of old mice with young blood, but these are genetically matched animals, and in people, we do not have our own identical but much younger twins.

How do you propose to balance the cocktail of factors in aged blood to promote a youthful tissue environment?

We are working on the NextGen blood apheresis devices to accomplish this. We are collaborating with Dr. Dobri Kiprov, who is a practicing blood apheresis physician with 35 years of experience, and he is interested in repositioning this treatment for alleviating age-related illnesses.

Do you think a small molecule approach is a viable and, more importantly, a logistically practical approach to calibrate all these factors compared to filtering aged blood?

Yes, it is a very feasible alternative to the NextGen apheresis that we are working and publishing on.

Even if we can "scrub" aged blood clean, is it likely to have a long-lasting effect, or would the factors reach pro-aging levels fairly quickly?

That needs to be established experimentally, but due to the many feedback loops at the levels of proteins, genes and epigenetics, the acquired youthful state might persist.

Ultimately, could a wearable or an implanted device that constantly filters the blood be the solution to these quickly accumulating factors?

Maybe, but the first step of a day at a NextGen apheresis clinic once every few months might be more realistic.

What do you think it will take for the government to fully support the push to develop rejuvenation biotechnology?

Clear understanding of the current progress and separating the real science from snake oil is very important for guiding funding toward realistic clinical translation and away from the myth and hype.

Link: https://www.leafscience.org/conboy-interview/

Comments

Undoubtedly, old blood is a major source of added aging in adults and elderly when compared to youth. If only we could filter out the aging peptides and encourage/increase the good youth producing peptides in our blood. Most likely the old peptides turn off hundreds of youth producing genes as we age so anything we can do to turn on these genes again would be beneficial to our longevity as well. Perhaps one thing we can do already is take health producing diuretics like green tea and/or coffee to stimulate our kidneys to flush out the bad actor peptides on an increased basis.

Posted by: Biotechy at January 19th, 2018 8:33 AM

PS: In addition to kidney filtering and cleansing of the blood, you also need an active, healthy liver to transform bad peptides in the blood stream to harmless non-aging molecules that can be removed via the bile system, or other actions of the liver.

Posted by: Biotechy at January 19th, 2018 9:46 AM

This addresses the hallmark altered intercellular signalling and has the potential to mediate systemic inflammation and encourage regeneration. While it isnt a prinary hallmark it could still be beneficial and relatvely easy to implement. So lets test it before drawing any conclusions here.

Posted by: Steve Hill at January 19th, 2018 12:27 PM

For a variety of reasons I have done a lot of research on aphersis. The current filtering technology is not at all specific, and there is no reason to believe that will change in the foreseeable future. One might as well just donate blood, which is what I do once a month, maybe not practical at that frequency for most people, but my Red Blood Cell counts and hematocrit levels run at the high end of normal.

Posted by: JohnD at January 19th, 2018 1:33 PM

John this isnt quite the same. Its next generation tech they are developing and should allow calibration of cytokines. Dont be so fast to give in, they have been working on this for over a decade and are now at the point of creating next gen tech to do the job. Just wait and see what the data shows.

Posted by: Steve Hill at January 19th, 2018 3:34 PM

I have filmed Irina and Michael at length and I don't think Reason has it correct. When you change storm cell activity and create younger tissues, it may well have an epigenetic effect,
actually unraveling age via feed back loops. Reason is a bit stuck on a purist view of Aubrey's
theory. Furthermore Reason, with regard to Rapalogues, there are experiments combining rapamycin rifampicin and allantoin where in the medium lifespan of c elegant was increased 100% and the maximum 80%/. These other compounds affected pathways besides mtor and CR. The effects were additive, This means the jury is out with regard to the degree of lifespan increase in other animals, including us. Reason, I find your blog informative but you are a bit too stuck on one theory and continually keep saying "IT won't do much" - Major scientists I know including David Sinclair and Brian Kennedy disagree with you as do I.

Posted by: Robert Kane Pappas at January 20th, 2018 10:59 AM

@Robert Kane Pappas: I harp on because I think that size of effect in humans is of paramount importance, and that the size of effect is not likely to be large for non-SENS approaches. All stress response enhancement approaches that increase life span to a sizable degree in short-lived species are not expected to do much of anything to human life span, add a few years at most, and will likely be of the same order of benefit as exercise and calorie restriction at best when it comes to health benefits.

Adjusting signaling is based on young/old factors overlaps with stress response enhancement, and may touch on other things, but I think that the people working on that have yet to prove that a treatment will do much of anything lasting in humans - that removed bad factors won't just be replaced again immediately, or that delivered good factors will produce lasting, sizable change. Since these therapies do not address causes, they only try to override intermediate consequences, it seems most likely that they will be (a) not so great, as the damage will still continue to cause all of the other, non-overridden problems, and (b) therapies that will have to be taken continually. Things that have to be taken continually and still don't deal with more than a tiny fraction of the issues are great for drug companies, not so great for patients.

Posted by: Reason at January 20th, 2018 11:19 AM

" ... is a bit stuck on a purist view of Aubrey's" ... just a bit? This individual cannot accept anything else than the dogma that was established by degrey. And the crowd here is the same. Sound like a cult? Even a study is coming from prestigious teams they rejected. The individual here goes around, talks in fancy words but still cannot accept what a study concludes. That was how the church rejected science evidence hundreds years ago. But comes at no surprise as sens is the same, people are calling deGrey "thick head" as he cannot accept any studies that contradict his ideas with which he started. (just look at his obsession with "no genes that hasten aging" (https://www.ncbi.nlm.nih.gov/pubmed/25902458) versus (just) recent studies (https://www.nature.com/articles/s41467-017-00899-5#Sec2, http://www.cell.com/cell-systems/fulltext/S2405-4712(17)30053-4, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595686/ etc.). Simply put it, this individual has tons of time at his hands and just "copy-and-paste" whatever deGrey/sens repeat. They all hope that by keep repeating same thing it will become true. Fortunately for us, there are real scientists that work in this field and they are not into whishful thinking like deGrey. Funny enough, look at the recent study published by AgeX (where deGrey got a position last summer): https://www.businesswire.com/news/home/20180102005228/en/AgeX-Therapeutics-Identifies-Genes-Implicated-Tissue-Regeneration

Posted by: abc at January 20th, 2018 7:52 PM

abc, if you know of any framework besides SENS that should theoretically be able to cure aging, please let us know. Otherwise, why should we care?

Posted by: Florin Clapa at January 21st, 2018 1:34 AM

@abc
There's a difference between science and engineering. Aubrey can be completely wrong with some of his ideas and still end up with a result that works. Scientific accuracy is not very high in the priority list of engineering projects, because you can identify and fix the problems later or buy a replacement from someone else that got it right. What matters is that you get stuff done under time and money constraints.

Posted by: Matthias F at January 21st, 2018 6:59 AM

@abc, while I agree there are some people who are dogmatic here and closed to other approaches, you are out of line. If you have a critique of SENS that is worthy of debate then go ahead rather than indulging in name-calling and ad homs.

All that matters is the data anyway and if SENS is wrong about something then its wrong and it will be shown to be wrong in due course. Best thing to do is test it and find out because engaging in pointless slap fights defending pet theories is a waste of time.

Posted by: Steve Hill at January 21st, 2018 7:00 AM

Reason, I suspect you might have forgotten about the original point of the Conboy research. It was never to just remove pro-aging factors because they're bad for you. It was to create a more favorable environment for stem cell growth, both natural and therapeutic.

Posted by: Slicer at January 21st, 2018 7:56 AM

@Matthias F - Makes an important point to remember in all of this discourse

Being scientifically wrong, but translationally right, was the basis for much of the modern pharmaceutical industry's success and wealth generation in the 20th century

Being scientifcally right, but translationally wrong, is a very dangerous path, as it can take down and place major research areas on ice for long periods of time

We saw this in the 1990s with sepsis drug development, and here we sit 30 years later with shuttered programs, no answers and still very high death rates

More recently, witness Pfizer's recent surrender to all Alzheimer's disease R&D - if such moves snow ball through the system it could hinder all Alzheimer's work for years to come, as the Wall Street, life science priavte equity, small biotech, etc. chain will stop operating

We must all be scientifically and translationally right to make life / health extension happen

Posted by: Ira S. Pastor at January 21st, 2018 8:30 AM

I have to say, I think the Conboy approach is a bit of a stab in the dark - because we just don't know enough about various transciption factors and their effect on gene expression. However I don't think the intention of this work is just tinkering around the edges - the idea, I believe, is nothing less than an epigenetic resetting of the aging process.

Aubrey isn't actually that dogmatic; I found him to be quite open about alternative approaches when I asked him a question. I think those of us who support SENS should be careful though not to lump all alternative approaches in with the tinkering with metabolic rate crowd.

Posted by: Mark at January 21st, 2018 8:34 AM

@Mark "I think the Conboy approach is a bit of a stab in the dark" I think you are a bit off track here with this statement. Irina and Michael have been steadily exploring these very interactions for the past 15 years what they are doing is based on good understanding of how to restore stem cell activity. Their data has been a solid progression of what they have learned.

You are correct about this being more than tinkering, the altered signaling environment is an aging hallmark and what they are doing isn't tinkering. Yes, altered intercellular signaling is lower down the hallmarks hierarchy but given the feedback loops involved it has great potential. Far beyond simple tinkering with metabolism, a phrase that gets thrown around far too often.

"Aubrey isn't actually that dogmatic; I found him to be quite open about alternative approaches when I asked him a question. I think those of us who support SENS should be careful though not to lump all alternative approaches in with the tinkering with metabolic rate crowd."

Yes, this! Absolutely spot on Mark!

Posted by: Steve Hill at January 21st, 2018 9:52 AM

@abc: Whether someone's position is dogmatic or not is not decided by how often it changes, but by how solid its arguments are. Reason has given plenty, solid reasons why SENS is a much better approach than the others. That's not dogmatism at all, that's solid conviction.

Posted by: Antonio at January 21st, 2018 12:58 PM

Regarding Aubrey's opinion on 'tinkering with metabolism', well, I can't speak for him, but nevertheless, deducing from what he often says in his talks, I think that he is all in favour of research into those other approaches because:

(i) He can be wrong about SENS. This doesn't mean that he thinks that the other approaches are as likely as SENS to succeed.

(ii) SENS can arrive later than expected/desired, so it's sensible to have a plan B or C in the meantime, even if it only provides you with a couple of years of life extension. This doesn't mean that he thinks that those approaches are faster, cheaper or will provide more than a couple of years. In the same vein, he is all in favour of exercise and CR, even if he doesn't practice them himself and don't expect more than 4-5 years of LE from them.

Posted by: Antonio at January 21st, 2018 1:13 PM

@abc: Regarding your links, "genes that exist to hasten aging" is not the same thing than "genes that modulate repair". De Grey makes a precise definition of the former in his paper, and it doesn't apply to your examples. After all, genes that mimic CR effects (like the genes discovered by C. Kenyon) are also genes that modulate repair, and have been known for a long time. He is not so stupid to ignore that, nor are his referees.

Posted by: Antonio at January 21st, 2018 1:37 PM

And the pointless slap fight continues :)

Posted by: Steve Hill at January 21st, 2018 2:48 PM

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