The Dark Matter of Senescent Cell Clearance Research: Other Approaches and Quiet Research Groups

There is no such thing as a scientific breakthrough. Advances in science and its application don't emerge from out of the blue, especially in very complex fields such as medical research, where any meaningful progress requires a team, and in very close-knit fields such as aging research, where everyone knows everyone else and at least a little about what they are working on. If the latest news looks like a breakthrough to you, that just means that you didn't know much about the people who spent years working on the foundations, the incremental advances, and the early prototypes. And why should you? You have your life to live, your own work to get on with. There is far too much going on in the world for any one individual to notice.

That is just as true of me as anyone else. I certainly don't have a view of every interesting corner of the research community, and even now there are no doubt numerous scientists working on projects relevant to the SENS model for human rejuvenation through repair of cellular and molecular damage whom I have never heard of. Even the highly networked folk at the SENS Research Foundation are surprised by what turns up some days, and they have far more insight than I. One of the consequences of rapid progress in biotechnology is that people outside the core aging research community have the ability to make useful and important contributions. Most of the technologies proposed as means of damage repair to treat aging did not originate in the aging research community, and I'd expect that state of affairs to continue as new options arise. So if you have a few fellows in a well-equipped lab in India or on the other side of a language barrier in China, tinkering on a possible approach and actually getting somewhere interesting when it comes to a proof of concept, it is quite plausible that we'd never hear anything of it until after the fact.

Frankly, it's hard enough just to keep abreast of what is going on in the US. Take senescent cell clearance for example; the demonstration in 2011 of improved health in accelerated aging mice via removal of senescent cells was clearly a wake up call for a number of researchers. In what is a comparatively short time for the research community, we have seen the recent publication on the use of existing drugs to clear senescent cells in ordinary mice, showing improved healthspan as a result, and a startup company was funded by the Methuselah Foundation earlier this year to have a go at commercializing a different approach to the removal of senescent cells. That is just the stuff that makes it to the point of press release and news in this community, however. It is not all that is going on, and the 2011 technology demonstration wasn't a sudden breakthrough from nowhere: work on cellular senescence with an eye to selectively destroying these unwanted cells was underway for years before that point.

For example, Cenexys has existed since 2009 and claims to "develops therapies to clear senescent cells from the body to treat age-related diseases." Perhaps it is a dead venture, judging by the lack of news, but perhaps not; the principal director certainly has an interesting and successful history. Then there is SIWA Regenerative Medicine, a company that has apparently also been working on senescent cell clearance for a while. Being first alas often means being bypassed at some speed by later ventures, but SIWA seems to be alive and kicking:

SIWA Regenerative Medicine

We have developed inventions that we believe can retard or reverse the aging process, reduce inflammation and enhance stem cell transplant success by promoting tissue and organ regeneration. We believe these inventions also can be applied as therapies in lessening the impact of diseases associated with aging. Specifically, we have developed processes for identifying and removing senescent cells that inhibit cellular regeneration to obtain the recognized benefits in health and function associated with the results of such cellular regeneration. We have filed multiple families of patent applications covering our inventions.

We were the first to publish a practical description of selectively removing senescent cells in order to retard or reverse aging. In a November 2011, paper that appeared in the journal Nature, other researchers reported creation of an artificial system that independently confirmed the soundness of the scientific principles behind the approach and other intellectual property that we published years before.

SIWA's Approach To Clearing Senescent Cells To Increase Healthspan

SIWA Regenerative Medicine Corporation announced today that Lewis Gruber, founder, CEO and inventor of SIWA's injectable drug-based approach to clearing senescent cells for increasing healthspan, will join scientists from Charles River Laboratories at 2:45 p.m. on March 23, 2015 in San Diego at the Society of Toxicology Annual Meeting to discuss and present SIWA's demonstration of successful use in naturally aged mice of a monoclonal version of SIWA's drug candidate. The results of the work performed by Charles River for SIWA include an increase in gastrocnemius muscle mass and reduction of a senescent cell mRNA marker to the level of young mouse controls.

The company has made some interesting patent filings over the past decade, such as Selective Removal of Cells Having Accumulated Agents:

The present invention makes use of the discovery that the differential resonant frequency of a cell caused by the accumulation of at least one agent that causes, or is associated with, a pathological or undesired condition, such as proteins, lipids, bacteria, viruses, parasites or particles, may be used to distinguish and eliminate cells in which the accumulated agent leads to a difference in the resonant frequency of the cell, by applying ultrasound treatment. The cells associated with the accumulated agent have a resonant frequency which is distinct from cells of the same type. By selecting the frequency of the ultrasound applied to the tissue to feed energy into the resonant frequency, the cells with the accumulated agent will be destroyed or induced to undergo apoptosis.

"We have developed inventions that we believe can retard or reverse the aging process, reduce inflammation and enhance stem cell transplant success by promoting tissue and organ regeneration."

Excuse me if I take these claims with a gigantic grain of salt. There's almost nothing on the site, except a self-indulgent "Egypt Trip" page.

"In human patients, this would at a minimum require that the patient undergo gene therapy to be genetically modified in order to have their senescent cells removed."

You can't just throw this out there without backing it up. Where's the research? What's the approach? What do the modifications involve?

"SIWA employs ultrasound and antibody technologies which may be applied to any patient without genetic manipulation. Thus, for any partner interested in retarding or reversing aging or its consequences, we have both a strong legal position and more practical products to offer."

Really? Like what? And why would your "legal position" matter if you've managed to reverse any aspect of aging?? (Talk about burying the lede!)

No list of staff, no explanation for anything it says, website is unimaginably sparse, no link to research papers- nothing of value except wild claims and a lot of "copyright 2012". I call total BS on this whole thing, and I'm pretty sure that their entire strategy is, in fact, patent trolling; they've patented a bunch of things that they think might work, and are waiting until someone else actually makes them work.

Posted by: Slicer at April 8th, 2015 6:08 PM

Yup. 100% patent troll. Just look at this BS:

"Preferably, the vaccine used to vaccinate a human contains from 1 microgram to 100 milligrams of at least one AGE antigen, including 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 400, 800 or 1000 micrograms, or 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80 or 90 milligrams. The amount used for a single injection corresponds to a unit dosage." And the even longer list of AGE-proteins.

This whole thing was intentionally written to be as broad as possible, as are all of their other patents. These people don't actually have an anti-AGE vaccination or anything else. They're just going to make legal threats against the people who do. Absolutely despicable.

Posted by: Slicer at April 8th, 2015 6:26 PM

@Slicer: The thing that makes it look legitimate, albeit a very small venture, is the presentation at the conference. That's a real event.

Whether or not their research is good is another topic entirely. But to me this looks like any number of small life science ventures that aren't making it to the point of success, but aren't ready to call it quits yet.

One of the things about small borderline viable life science companies in general is that you can't read much as to their viability from a bad or non-existent website. They don't care about a web presence. That's always been the way while I've been watching the industry; until they have significant size and funding there is simply no reason for them to have a website or a professional designed look. It's just extra work for no gain.

Posted by: Reason at April 8th, 2015 6:36 PM

Reason: I'd love to have seen that presentation; it's in the toxicology program but not mentioned anywhere else. I've been looking up Lewis S. Gruber's patents, not just under SIWA Corporation, but under his own name. With and without middle initial, there's a lot more stuff there.

Even their site says straight out: it's not about what they've done, not about what they've developed, but what they've patented. I simply do not believe that the company owned by "Misty and Lewis" has done actual research into any of the things they've laid claim to; in fact I severely doubt, without any direct evidence, that they have even contracted with anyone who has, other than (possibly) Charles River Laboratories, which (if you read the program of the toxicology conference) is the group that actually gave the presentation.

A company filing patents on things that it has not actually made to work is the hallmark of a patent troll.

Posted by: Slicer at April 8th, 2015 6:55 PM

@ Reason - maybe you can contact them and ask couple things and post their answers here in an updated version of this post? I agree with Slicer: their web site is not very convincing. But I do hope, they are for real, as we all want progress on all fronts.

Posted by: Adrian Crisan at April 13th, 2015 8:21 PM

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