Fight Aging!

The SENS Research Foundation is one of the few organizations presently focused on developing medical technologies that will produce rejuvenation in the old. The Foundation researchers and staff undertake targeted research programs in areas that are not getting enough attention from the mainstream life science community, and engage in advocacy to convince more of the research community to work on the goal of reversing degenerative aging, thus preventing age-related disease, frailty, and disability, and extending healthy life.

A newsletter from the Foundation arrived today, with a link to the Foundation's 2012 annual report (PDF). Good news on the budgetary side of things is the order of the day, and the Foundation is continuing to grow its research efforts. The total budget in 2012 was $3 million, in comparison to the $1 million only a couple of years earlier:

We are pleased to report that, in 2012, SENS Research Foundation was able to support expenses that were double those from the previous year. This was made possible through not only the continued support of our generous donors, but the first in a series of annual disbursements from the de Grey family trust, which together caused SRF's income to increase by about $2 million.

As a research-based outreach organization, the scientific work that we fund plays a critical role in our mission. For this reason, we have focused our growth on our extramural research program, tripling its size by adding more than $750,000 of funding. This aggressive expansion has led to the addition of nine new projects, including two at the Wake Forest Institute for Regenerative Medicine, bringing our total funded to seventeen. Meanwhile, we were able to add $300,000 to our intramural research budget, bringing a third major project, more staff, and new equipment to our Research Center in Mountain View, California.

Simultaneously, we built SRF Education into a larger and more robust educational program, creating our first online course and a successful summer internship program that involved both our Research Center and the Buck Institute for Research on Aging. This has set the stage for further growth in 2013, which will include the development of more coursework and the addition of new internship campuses.

Overall, our expenses in 2013 should increase by an amount equal to 2012's increase. Given our secure base of funding sources, we expect to sustain this higher level of operation indefinitely. We are deeply appreciative of the individuals and foundations that enable us to pursue our mission through their support. We would like to thank Peter Thiel, Jason Hope, the de Grey family trust, the Methuselah Foundation, and the many other donors who make all of our efforts possible.

If you read through the report, you'll find good overviews of the present research programs supported by the Foundation, as well as news of recent progress.

Lysosomal Aggregates

Researchers funded by the Foundation are searching for bacterial enzymes that can be safely introduced into the body to break down harmful metabolic byproducts that build up in the lysosomes within cells, degrading their ability to keep up with cellular housekeeping, and contributing to a range of age-related conditions. There are many different types of chemical gunk that building up in the lysosome, so researchers have so far focused on those best known to the research community.

At the SENS Research Foundation Research Center (SRFRC), our Lysosomal Aggregates team is working to efficiently deliver promising A2E-degrading enzymes identified in our earlier research into the lysosome of cells. One in particular (SENS20) has demonstrated tremendous efficacy in degrading A2E not only in vitro but in A2E-loaded retinal pigment epithelium cells.

In 2013, the team will put a recombinant form of SENS20 to the test, assessing its ability to degrade A2E in vitro and in retinal pigment epithelium cells, and verifying that it is not toxic to the cell

It has to be said that it is very pleasing to see the Foundation at the stage of giving the characteristic drug/therapy candidate names (SENS20 in this case) to the results of their work.

Mitochondrial Mutations

Our mitochondria become damaged with age, causing a range of catastrophic consequences to our cells and tissues. The SENS approach to fixing this is to put backup copies of vulnerable mitochondrial genetic material into the cell nucleus. The challenge here was never getting the genes into the nucleus, as that's just straightforward gene therapy, but rather getting the proteins from those genetic blueprints back into the mitochondria where they are needed. This was slow going until fairly recently, when a potential game-changing advance emerged from the broader research community.

It sounds like the SENS Research Foundation folk are working to integrate this new approach into their efforts, as it could in theory allow all the necessary genes to be moved into the nucleus via the same basic method - so get it working once and you're done.

SRF-RC scientists are now working to master and refine a superior method for accomplishing this goal. Our team has taken four cell lines from patients suffering from severe diseases caused by inherited mitochondrial mutations, and made stable lines that express their improved mitochondrial gene constructs. They have begun collecting data confirming the targeting of gene transcripts and proteins to their mitochondrial locations, and the functional activity of the mitochondrial energy system, in such re-engineered cells.

I am very impatient to see a demonstration of mitochondrial repair or DNA replacement running in a mouse life span trial - it is my belief, based on the range of research I've seen over the years, that mitochondrial damage is the dominant cause of degenerative aging, and I'm looking forward to seeing just how right or wrong that hypothesis might be. It's not unrealistic at this point to think that ten years from now we'll have that data in hand.

Extracellular Matrix Stiffening

Crosslinks such as advanced glycation end-products form relentlessly in our tissues, gumming up protein machinery and causing a fair portion of the visible symptoms of skin aging - and worse, the loss of flexibility in blood vessels and other important tissue structures. Old skin I could live with, but you can't live with old blood vessels; they'll kill you in the course of time. The short history of attempts to develop therapies to break down AGEs has been a short history of frustration, with only very limited success to date. Fortunately, we are now past a critical point of discovery regarding AGEs, which is that in human tissue they overwhelmingly consist of a single compound called glucosepane. Unfortunately, beyond the SENS Research Foundation next to nobody cares to do anything about this aspect of aging.

Late in 2012, we announced the establishment of our new SENS Research Foundation Laboratory in partnership with the University of Cambridge Institute of Biotechnology. In collaboration with Dr. Spiegel's lab, the SRF Cambridge center will initiate work on new agents to cleave apart crosslinked proteins, restoring youthful elasticity and buffering capacity to arteries. The specific molecular target will be glucosepane, the main crosslink that accumulates in aging human arteries and other tissues.

Dr. Spiegel has already developed a way to synthesize glucosepane in the lab; this artificially-produced glucosepane can now be used to develop reagents that can rapidly and specifically detect proteins that have been crosslinked by it.

The Cambridge group has been working on methods of extracting crosslinked proteins intact from the tissues of dogs and marmoset monkeys, and to measure glucosepane cleavage in the test tube and in animal and human tissues. It is clear from this research that none of the commercially available monoclonal antibodies against related crosslink molecules are able to cleave glucosepane to any significant degree, and many are useless. All of these findings further emphasize the importance of this project in developing novel crosslink-breaking therapies.

Other Research Programs

A range of other current research programs are given just as much attention in the annual report. I hope that the notes above encourage you to look them over. This is what the future of longevity science looks like: deliberately and carefully working to reverse specific forms of damage that occur in old tissue but not in young tissue. It is a world away from the old school drug discovery process in the Big Pharma mainstream that aims only at modestly slowing down aging - the sirtuins, and resveratrol, and rapamycin, and all the other potential and so far largely disappointing age-retarding drugs. SENS is the only path forward that is likely to produce significant rejuvenation in the old when its therapies are ready for clinical use.

For you and I to have a good shot at living far longer than our ancestors, the SENS approach must come to dominate the mainstream of aging research, displacing less effective and more expensive approaches. Fast progress requires large budgets and hundreds of researchers. The sooner that this happens, the more likely it is that we will still be alive and in good health when rejuvenation therapies arrive.