The Edmonton Symposium on Aging was an interesting mix: scientists from all over the interdisciplinary field of aging research ,and educated laymen who have a keen interest in our work. As the research was all over the map it is a bit hard to categorize, but I’ll try to do so roughly here:
- Stem cell therapy
- Tissue Regeneration
- Re-engineering the Body
- Diseases of Aging
- Mitochondrial Aging
- A Party for Young Old People
Irina Conboy (my boss) presented our lab’s currently in-press data on how an aged tissue environment negatively affects the ability of muscle stem cells to differentiate. The proximity of ESCs, however, can locally rescue the affects of a “polluted” niche. We are currently investigating the soluble factors that regulate the ability of cells and tissues to renew and regenerate.
Amit Patel presented some good data from his work on injecting bone marrow-derived MSCs (mesenchymal stem cells) into the heart (of both rodents and patients) to treat heart failure. The mechanism is hazy at best, but it seems to work! The cells (self-derived) do not graft, but probably help through paracrine effects.
Ellen Heber-Katz gave an update on the MRL (Murphy Roths Large) mouse story. She has discovered that this regenerating mouse breaks down the basement membrane in the vicinity of an injury (apparently similarly to other, more “traditionally” regenerating creatures such as salamanders). Matrix metalloproteinases secreted by inflammatory cells recruited to the wound site are apparently essential to this aspect of the healing process.
Geoff Goldspink gave a really interesting talk about MGF, a unique alternative splice form of IGF-1 that is activated extremely soon after muscle injury. The isoform stimulates muscle stem cell self-renewal, and then shuts off, so that stem cells can differentiate and repair muscle. He showed some very convincing data on enhancing rodent muscle-building with MGF supplementation. Novus Biologicals holds the patent and is developing both protein- and drug-based therapies for muscular dystrophy.
Aubrey de Grey rallied the troops with his rousing speech encouraging us to take an engineering approach to tackling the problem of the maladies of aging. His point boils down to the idea that if someone finds something valuable enough, they will find a way to take care of it and keep it working. Examples of this are old cars. Most of them weren’t meant to live forever, but we find a way to make them immortal. Some of them (e.g. the VW) weren’t even very well built to begin with, but they are popular, so people find ways to keep them working.
Bruce Rittmann is a bioremediation guy who has been running with an idea that Aubrey de Grey has been pushing for the past few years: using a bioremediation strategy to target bodily waste products that cannot be broken down, e.g., lipofuscin. 7-ketocholesterol is apparently the most abundant such indigestible component of foam cell lysosomes. Rittman and co-workers screened for bacteria that could survive on a diet of 7-ketocholesterol and found one strain. Now they are doing a genetic screen to identify the gene of interest.
Supercentenarians – people aged 110 and higher, are a rare breed (1 in 5 million make it that far). The Supercentenarian Research Foundation (SRF) is dedicated to honoring and studying these “super-humans.” Doros Platika spoke on behalf of the SRF. Two interesting facts about supercentenarians:
- They don’t get brain plaques or any autopsy-visible brain degradation.
- Most seem to die from transthyretin (TTR) amyloidosis.
While the group has very little data and very few subjects to study, a clue about what we might be up against if most major diseases were cured and people started living past 100 could be extremely valuable.
There was a really exciting talk by Ashley Bush about a novel class of compounds being developed to treat Alzheimer’s. The idea is dealing with the problem of metals in Aß plaques. He rejects the idea of chelators to deplete metals (he thinks zinc is the most important) from the brain, since total brain Zn2+ is actually reduced in Alzheimer’s brains, and depleting it further would presumably be bad. Therefore, he has focused on compounds that bind zinc with fairly low affinity and instead specifically disrupt the Aß – zinc interaction. Dramatic results were achieved in mouse models of Alzheimer’s; clinical trials are encouraging and well underway. The most current incarnation of the drug is called PBT2 and is being developed by Prana Biotechnology.
Patrick Lee reported work on treating cancer with live viruses – not for gene therapy, but to sic the virus on the cancer and let them battle it out — seriously! Dr. Lee is using reovirus, the advantage being that the virus is ordinarily quite harmless, and is quickly completely cleared by the immune system. The reason that it works is that the virus is supported by Ras, one of the most common oncogenes, which Lee believes greatly enhances viral replication. The virus is extremely lytic, so it quickly kills Ras-positive cells. Drawbacks to this approach are that the virus is easily cleared by the immune system and therefore may need to be used in combination with immunosuppression. (And, of course, your tumor needs to be Ras-positive.)
I recently reported that at the AACR aging meeting, the mitochondrial theory of aging took a blow from some negative data. At Edmonton the ship started taking on water, as Konstantin Khrapko showed a lot of negative data from some very careful mitochondrial aging experiments. He holds out hope that even though mitochondrial aging and its effects cannot be detected at the system-wide level, damage to mitochondria in specialized tissues may be important. He showed some data suggesting that this may be the case in the substantia nigra of the brain.
The Classics are one of the oldest rock bands in Canada, and they played at the after party. They’re actually really good. This conference didn’t just talk about how to make you young again, it actually did! You’ve never seen distinguished scientists like Irina Conboy, Aubrey de Grey, and Ellen Heber-Katz throwing it down on the dance floor like I did at the party.
Talk and poster abstracts are available online, and rumor has it that video of the presentations will be available soon.