10 replies to this topic

[circuitblue]

Hi everyone,

Are there many active scientists on this forum? I am very interested in brainstorming biogerontological experiments to perform, but am in direct contact with few scientifically active biogerontologists and especially those with medical knowledge (ie. an MD, if many exist). I currenty work part time in a genetics lab probing mitochondrial dysfuction in the germline via RNAi and mutant screens, and if my results in the next few months are good and obtained in not too long a time (since it is science, this is definitely a long shot) will later hopefully do mtDNA PCR (been trying to get it to work with large fragment amplification, might try picoGreen quantitative analysis), mitoTracker assays and maybe some other methods of assessing metabolic integrity of unique mutants to probe novel mitochondrial genes. While I've found these experiments rewarding, I hope in the next year or two (before I go through the getting-into-medschool process) to peform work more directly related to biogerontological medicine (somewhere...). Anyhow, if you are a scientist interested in discussing such things, please throw me a line or post here!

-chris
www.circuitblue.com
www.biologicalgerontology.com

[John Schloendorn]

Heh, I would not say many, but I think one can see a lively discussion going here lately. Do you have any specific proposals in mind? Out with it!

Btw, we have a forum under construction that will be more science oriented than imminst (like SAGE KE, but with a clear focus on extreme life-extension). We aim to scaffold the discussion among those biogerontologists (like you?) that would work to extend life span, but do not find themselves in a conductive community network.
Access to the construction site is restricted to full members at this time. We still have a big need for volunteers for that project, which includes leading positions. So if you think that's worth a shot why not drop by?

[circuitblue]

At present, I simply want to discuss the mitochondrial protofection paper which I'm sure you've all read (Khan, Bennett, 2004) with someone with a medical background as I have some ideas of how to further the experiment (just thought experiments it seems though, as I am ill-equipped to do more than genetics work at present). Problem is, Aubrey and I think the paper is severely lacking in details (I especially with regard to experimental details), and that hampers discussion somewhat. I am waiting for responses from some of the authors' collaborators, and if nothing comes of that I'll be sending emails left and right. Perhaps they have their eyes on an interesting patent...if so I and lot of other people would love to be in on bringing it to fruition for everybody.

Othere than protofection I, and my colleuge in the lab who is a physics postdoc (working now in genetics) have a couple ideas from mitochondrial related ones to some regarding experiments devised to combat accumulated waste products that may critically interfere with cell function, ie. perhaps lipofuscin. While these theories don't necessarily "sound as pretty" in putatively being a primary cause of age, it has nothing less going for it than the other ones and there seems a serious lack of knowledge on this front since Strehler passed away a while ago.

Anyhow, I'd love to participate in more serious discussions related to scientific biogerontology. When is this forum going to be "constructed," and how might I drop by? Thanks for the responses!

[John Schloendorn]

The science forum project is at a very early stage and progress is slow mainly due to lack of volunteer time. People are still doing the web programming and I have drafted a few editorial texts basically. But you can get a fair idea of what it's going to be like from the project forum, from where we orchestrate the work.
The easiest way to get there is by becoming a full member. But if, for some reason, you don't want to, but are serious about contributing to the science forum, you might ask BJKlein or Caliban to grant you access rights.

[manofsan]

Hi gentlemen,

I decided to email Dr Smigodski directly, and he replied back to me that he could not reveal the details of this research, as it has not been fully published yet. He does however feel that the technique holds much promise, and did in the meantime give me a link to a paper that he has already published:

http://www.ncbi.nlm....t_uids=15377877

To be frank, I'd read this summary capsule before, along with that May2004 posting by Dr Smigodski, but if anyone has full access to the full article and would care to share it, please go ahead.

I just want to focus on one sentence: "With protofection, the mitochondrial genotype can be altered"

I'd wonder if that might allow for doing more than just repairing the genome with pristine genes -- could we perhaps substitute in mtDNA from avian mitochondria, or whales, etc, to improve on what mother nature gave us?

Comments?

[John Schloendorn]

here ya go

Attached Files

•  2004_mt_gene_therapy.pdf   735.4KB   78 downloads

[circuitblue]

I'm confused, does anyone know Dr Smigodski's relation to the above paper? The paper says the authors are Khan and Bennett. Did he perchance take long to response manofsan? I have been awaiting a reply to some questions I have emailed him...

With regard to "more than just repairing," this is a completely moot point at present for the following reasons. First of all, we can't even repair the genome now, and this is why a number of individuals suffer from a plethora of mitochondrial diseases with symtoms ranging from muscle aches to infant mortality. Second, "just repairing the genome" would be an absolutely stellar feat in that it would both provide a cure for these afflicted individuals and also provide a means to test the efficacy of the mitochondrial theory of aging. Third, aside from*possibly* reducing the number of genes in the mitochondrial genome by moving them into the nucleus (which is more difficult and more ridden with complications, theoretically if the above paper is actually true). To try and improve the genome at present would sort of be like giving a broken-down car in the dump a new paint job without fixing the engine.

Anyhow, unless this group is holding out for a patent or some crazy results they don't want competition for I am becoming increasingly skeptical of their resistance to publish a cohesive paper. I direly hope their results are not falliciious, as if they aren't it will mark a great stride towards efficacious mtDNA repair in vivo with humans.

[manofsan]

Hi circuitblue,

Based on that article I posted under Mitochondrial Remediation, it would appear that Dr Smigodski and Dr Shahryar Khan are both working on the same field of interest, though I'm not sure if they're jointly collaborating.

Okay, fair enough, talking about remodelling the mt-genome after other more long-lived creatures may be getting ahead of the game right now.

As you say, the mere restoration of aged mt-genomes to a more youthful pristine state would be a fabulous accomplishment in itself. I don't know why a further paper is not forthcoming. Perhaps it's because there aren't enough competitors pushing forward in this field. Well, even if Smigodski et al are fakes, the assault on the mt-genome is increasing, and the more who become aware of what a juicy target the mitochondria is, the more quickly the challenge will be met.

[Cyto]

Mmmm, the .pdf doesn't work for me. John, would you be willing to try a repost or to send it via email?

Thanks

[jaydfox]

manofsan

...the assault on the mt-genome is increasing, and the more who become aware of what a juicy target the mitochondria is, the more quickly the challenge will be met.

Indeed, the field is ripe, especially with the recent rebirth of the MiFRA. Allotopic expression, increased repair, highly targeted and concentrated antioxidants, mutant DNA replacement, ablation of COX-negative cells... There are many angles being pushed, and I just don't know enough about the field to know who's going to be first to the marketplace, or which method will have the best results.

But I'm pretty sure that even if the most promising approach fails, there are plenty of backup approaches, such that we should not be worried whether mtDNA damage can be effectively controlled by a marketable procedure in the next 20-30 years.