February 2014

February 2014

Full Series of SRF Education Coursework Videos Now Online

 
SRF asked world-renowned researchers to participate in a series of lecture videos explaining how regenerative medicine can help treat and prevent the diseases of aging. We are happy to announce that the 10-part series of videos is now complete and available on the SRF website.
 
Learn more about stem cells, tissue engineering, cancer mitigation strategies and regenerative medicine from such luminaries as Dr. Daniel Kraft, Dr. Alan Russell, Dr. Judith Campisi, and Dr. Michael West on our Video Lecture Course page.
 
     
 
     
 

Supporter Profile: Jason Hope

 

1) How did you become interested in SENS Research Foundation's work?

 
It really started for me once I read the book “The Singularity Is Near” by Ray Kurzweil. It made me realize that we advanced technology so fast that we really left ourselves behind. I spent some time researching technology in the health industry and came across Dr. Aubrey de Grey. I quickly realized his unique engineering approach to fighting the diseases of aging was exactly what we needed to finally solve some of today's biggest killers and drivers of healthcare costs, including heart disease, stroke, and cancer.
 
2) Why do you think it is important for people to support SENS Research Foundation?
 
Although hundreds of billions of dollars have been poured into biotech and healthcare research over the past several decades, not much has changed about how we approach solving our biggest health problems. The wars on heart disease and cancer are far from over and little progress has been made against these diseases. SENS gives us a new approach that stands to alleviate a significant amount of human suffering in the near future. SRF's cutting edge research is going to really move us forward. It’s going to give us and our loved ones the ability to live longer, healthier lives and the more people that get involved, the faster this becomes a reality. 
 
 

 

 

Question Of The Month #1: How To Manage Mutant Mitochondria?

 

SRF is pleased to present a new monthly column. Expert science writer Michael Rae will answer one question from our inbox each month.  Please send your questions to foundation@sens.org and your question may be featured.

 

Q: Dr. De Grey says in his Mitochondrial  Mutations in Aging video that there are three principal ways to solve the problem of eliminating mitochodria with mutated DNA, but what seems to me the most straightforward method is not discussed. Why not simply selectively target the mutated mitochondria (since we can clearly identify them) and tag them  for mitochondria autophagy (by inducing damage, etc.) and thus selectively destroy the mutated organelles?

 

A: In principle, your proposal would be a great solution, but the key would be to find a way to selectively target mutant mitochondria, and there are no known ways of doing so at present. 

 
First, while it's true that we can identify such damaged mitochondria, we can only do so in cells isolated from the body and stained with various dyes, or heated up to break down the DNA into smaller chunks that are then analyzed — not while those cells and tissues are still present and carrying out their function inside a person's living body.
 
As yet, there is no known signal put out by mitochondria harboring large deletions (the main class of mutations that accumulate in aging cells) that we could use for the purpose you describe. That's all the more true since such mitochondria are minimally metabolically active and can no longer produce their own proteins.
 
Second, there's good reason to think that the endogenous way of tagging defective mitochondria for destruction in the lysosome actually drives the problem! You can read the details in Ending Aging, but under a model Dr. de Grey nicknamed "Survival of the Slowest," cells identify old, damaged, but non-mutant mitochondria by the damage they accumulate in their membranes from the free radicals that they are constantly producing. By contrast, mitochondria bearing these deletion mutations avoid destruction because they no longer have the ability to produce key proteins in their energy-producing machinery. Without these proteins, the main mechanism of energy production in mitochondria shuts down — and along with it, free radical generation ceases. In the absence of the constant bombardment of free radicals, these mutant mitochondria no longer suffer damage to their membranes, and as a result, they they evade the normal mechanism that would target them for destruction. Mutated mitochondrial DNA then accumulates, as only non-mutant mitochondria are consumed (Figure 1).
 

 

 

Figure 1. When cells are deprived of nutrients, they activate autophagy to non-selectively degrade and recycle proteins, many types of organelles, and other cellular components. By contrast, mitophagy is a selective process that specifically degrades mitochondria, either to eliminate damaged organelles or to cull excess numbers. Image ©2011 Nature Publication Group; reproduced from (1), with permission.

 

 
Once the first mitochondrion in a cell suffers a deletion mutation, this process appears to lead very rapidly to the elimination of all of the non-mutant mitochondria in the cell, leaving behind a cell completely taken over by mutants. We never find cells in a state of transition between all-healthy and all-mutant mitochondria.
 
Any system that therefore aims to prevent the expansion of mutation-bearing mitochondria would have to cull deletion-bearing mitochondria faster than the normal processes of mitophagy already apparently culls healthy ones. This system would have to be thorough enough — and durable enough — to prevent the selective "clonal expansion" from happening indefinitely, under the full range of metabolic states of the cell. Next, we'd have to ensure that this dual culling would not somehow harm the cell: this doesn't seem likely, since the mutant mitochondria are by their nature harmful, but it would have to be tested.
 
I can see at least two ways that a system used to identify mutation-bearing mitochondria and send them to the lysosome for disposal might be subverted over time. First, the system might require us to insert new genes into the mitochondria (to express a marker under conditions where the activity of certain components of the citric acid cycle were very high, for instance). But since the whole problem is that such genes can be mutated, it's likely that many mutation-bearing mitochondria (again, particularly the most important class, which bear large deletions) would have mutations that inactivate these very genes. Secondly, the signal tag itself could be degraded or damaged while the mutation-bearing mito is awaiting disposal.
 
The advantage of the approaches that we favor is that they bypass the need for the mitochondria to behave in any particular way (such as to express any particular protein or produce any particular metabolite), and make the presence or absence of deletions in the mitochondrial DNA irrelevant to the body. Because we will engineer an alternative means of getting the mitochondria's energy-producing machinery the proteins it needs to function normally (whether by putting backup copies in the nucleus, or by delivering the needed RNAs directly into the mitochondria), the mitochondria will function normally whether they have deletions or not. This means that deletion-bearing mitochondria (a) can keep producing energy in the cell, (b) don't cause the cell to produce the toxins that they normally do, and thus avoid poisoning the rest of the body, and (c) will once again be subject the standard mechanism of clearing damaged mitochondria out of the cell   thereby effecting what you propose by a circuitous route.
 
Reference
1: Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2011 Jan;12(1):9-14. doi: 10.1038/nrm3028. Review. PubMed PMID: 21179058.

 

REMINDER: SRF Summer Scholars Program Applications Due March 3

 

The search for undergraduates to participate in the 2014 SRF Summer Scholars Program continues. If you are a qualifying student (click here for eligibility guidelines), make sure to submit your application before the deadline of 12 AM PST on March 3, 2014.
 
If you know an undergrad who might be interested in participating, make sure and alert them to this paid opportunity to join researchers at several distinguished institutions, including SENS Research Foundation's own Research Center, to tackle the diseases of aging.
 

 

Again, the application period ends at 12 AM PST on March 3, 2014. No applications will be accepted after the deadline.To learn more, visit http://sens.org/2014-summer-scholars.

 

SRF In The News

 

 

Ce Chercheur Veut Nous Faire Vivre 1000 Ans, Paris Match (French language article).

 

 

Upcoming Events

 

The Royal Society of Medicine, RSM ICG-6 Interventional Cosmetics: New and controversial treatments, March 1, 2014

 

The Plato Society, Los Angeles, Live To 120 Plus - Utopia or Dystopia?, March 8, 2014, 8:30 AM - 3:00 PM

 

 
New SENS6 Video Content: Translational Research Challenges and More
 
New video presentations from the SENS6: Reimagine Aging Conference are now available. In addition to Dr. George Church’s keynote address outlining the latest advances in genomics and -ome technology, you can now also view Richard Barker's presentation on the challenges facing translational research, Dr. Brian O'Nuallain's talk on the therapeutic and diagnostic potential of innate and vaccine-generated antibodies, and others here on our SENS6: Reimagine Aging Conference Videos page.

 

 

        

 

We're adding new content as fast as we can process it, so be sure to check back frequently for new updates. 

 

 

 

 

 

 

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