make human live longer by genetic operations

[steelcat]

Are there any breakthrough to make human live longer by genetic operations?

[biohazard]

No, not really.

[jonmoulton]

Exon skipping therapy is in clinical trials now (http://clinicaltrials.gov/ct2/show/NCT00844597). This isn't a change in DNA, but an alteration of the splicing of pre-mRNA caused by dosing with a steric-blocking antisense oligo. It is a nucleic acid "operation", but perhaps not a "genetic operation" as it changes a gene transcript and not the gene itself. Here are a few recent references.

Wu B, Li Y, Morcos PA, Doran TJ, Lu P, Lu QL. Octa-guanidine Morpholino Restores Dystrophin Expression in Cardiac and Skeletal Muscles and Ameliorates Pathology in Dystrophic mdx Mice. Mol Ther. 2009 Mar 10. [Epub ahead of print]

Bauman J, Jearawiriyapaisarn N, Kole R. Therapeutic Potential of Splice-Switching Oligonucleotides. Oligonucleotides. 2009 Jan 6. [Epub ahead of print]

Wu B, Moulton HM, Iversen PL, Jiang J, Li J, Li J, Spurney CF, Sali A, Guerron AD, Nagaraju K, Doran T, Lu P, Xiao X, Lu QL. Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer. Proc Natl Acad Sci U S A. 2008 Sep 19;105(39):14814-9. [Epub ahead of print]

Svasti S, Suwanmanee T, Fucharoen S, Moulton HM, Nelson MH, Maeda N, Smithies O, Kole R. RNA repair restores hemoglobin expression in IVS2-654 thalassemic mice. Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1205-10. Epub 2009 Jan 21.

Moulton HM, Moulton JD. Antisense Morpholino Oligomers and Their Peptide Conjugates. In: Therapeutic Oligonucleotides, edited by Jens Kurreck, Royal Society of Chemistry 2008.

[biohazard]

Ok, maybe we need to define "breakthrough" then. What I meant, there isn't any treatment available currently that could be used to exted human life solely by manipulating our genetics. And as far as I know, there isn't one around the corner either.

However, there are many research lines that target such things, and they may have promising results like Jonmoulton mentioned. But I dont think these will be in practical use within the next few years. Our knowledge about these things keeps growing steadily, and I'd say it is a breakthrough when we first time manage to apply one of these theories on humans in practice. I bet that'll take a while, but of course with breakthroughs, you never know :)

[NatureTalk]

Hmm. Here's the tricky bit. On what evidence do we conclude that we're better off alive than dead?

[MrMistery]

on the fact that we are in control of our lives, but in control of what happens afterwards. there might be an afterlife and all that jazz, and if you believe in the more fundamentalist paradigm of life after death than life on Earth is simply a test. However, if all of that is not true then this might be very well all you get, and you better make the best of it. this is the view on which the very existence of medicine is based on.

[jonmoulton]

"Clinical trial", biohazard. In humans. Now. I conjecture you don't have DMD, but for those who do this has immediate life-extending potential. Here's what happens in dogs:

Video 1, Non-treated Dystrophic Dog, 7 months old

Video 2, Non-treated Dystrophic Dog, 7 months old

Video 3, Treated Dystrophic Dog, 7 months old
After 5 x Weekly 120 mg/Kg Morpholino Oligo Cocktail Injections.

Video 4, Treated Dystrophic Dog, 4 months old
After 7 × 200 mg/Kg Morpholino Oligo Cocktail Injections.

Video 5, Treated Dystrophic Dog, 7 months old
After 11 × 120 mg/Kg Morpholino Oligo Cocktail Injections.

Yokota T, Lu QL, Partridge T, Kobayashi M, Nakamura A, Takeda S, Hoffman E. Efficacy of systemic morpholino exon-skipping in duchenne dystrophy dogs. Annals of Neurology 2009 [epub ahead of print] doi 10.1002/ana.21627

NIH press release on Morpholinos for Duchenne muscular dystrophy in a dog model of DMD.

[biohazard]

Ah, my bad. Apparently I managed to miss that "clinical trial" part in your post. Now that is quite something, I must admit - I wasn't aware that so much progress has taken place on this area of research. I did my Bachelor's thesis on DMD research (including the dog model) several years back, and that time it seemed it would take longer to reach the clinical trial phase.

Also, I mistakenly thought that the topic of this thread was more about the life span of healthy individuals. Indeed, chances to extend someone's life who has some kind of genetic disorder are probably something we see much sooner.

Thanks for correcting me.

[steelcat]

Ah, my bad. Apparently I managed to miss that "clinical trial" part in your post. Now that is quite something, I must admit - I wasn't aware that so much progress has taken place on this area of research. I did my Bachelor's thesis on DMD research (including the dog model) several years back, and that time it seemed it would take longer to reach the clinical trial phase.

Also, I mistakenly thought that the topic of this thread was more about the life span of healthy individuals. Indeed, chances to extend someone's life who has some kind of genetic disorder are probably something we see much sooner.

Thanks for correcting me.

No, you were right, I asked how to extend the life span of healthy individuals.

[jonmoulton]

"Are there any breakthrough to make human live longer by genetic operations?"

I missed the healthy individuals implication. Caloric restriction may be an effective technique. At this time I don't know of any genetic operations for extending lifespans of healthy individuals that are near clinical trial stage. However, targeting a common mutant splice site of laminA which converts it into the protein progerin and causes nuclear membrane defects and other age-related pathologies might eventually be a useful approach.

Scaffidi P, Misteli T. Lamin A-dependent nuclear defects in human aging. Science. 2006 May 19;312(5776):1059-63. Epub 2006 Apr 27.

Scaffidi P, Misteli T. Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med. 2005 Apr;11(4):440-5. Epub 2005 Mar 6.