8 replies to this topic

[alc]

http://www.medicalne...ases/311012.php

 

http://www.cell.com/...4131(16)30245-5

[niner]

Oops...

back to the drawing board.

[corb]

All groups trying to reconfirm the Walker experiments were coming up with results which were leading up to this conclusion.
 

The conclusion does rise questions.
Can Follistatin help (notice I'm saying HELP not cure) with diabetes?
It seems in some cases it might:

http://www.nature.co.../mt201529a.html

Even more intriguing - by working on the pancreas not the muscles according to this study.

Follistatin is shaping up to be quite the therapeutic Swiss army knife - if the telomere therapy is found to be meaningless (something I strongly suspect will happen) at least in this Bioviva has a viable product.

[alc]

1. "Walker experiments" ? in other of your posts you keep repeating same thing "Walker experiments" - can you post some links to these? (I have a feeling that you are confused and mix the name with Amy Wagers ...)

 

2. "telomere therapy is found to be meaningless (something I strongly suspect will happen)" = yes, they already found + proven that ... lol

That is why recent study by Maria Blasco reinforces the TPE-OLD process.

So stay calm, these guys like: Maria Blasco/CNIO, Jerry Shay, Michael Fossel, George Church, etc. they  just like to waste their time. None of them are serious, there is only ONE group that is serious.

[alc]

Oops...

back to the drawing board.

 

Yes in some fashion is "back to drawing board", but at least something is known to influence the aging/rejuvenation process.

 

In scientific world it is much better to figure out something is not working or that is not the thing to look for, as opposed to reject studies and write a "question of the month" to calm the followers (you know what I mean).

 

And if you know how to formulate the question, you already have half of the answer. I think is very good they are clarifying things via studies, as opposed to opinions/articles.

 

Just wait for next studies and we shall see.

[corb]

Actually it's very much back to the drawing board because the first paper by the Wagers group (you're right it's Wager not Walker I'm not good with names I can admit when I'm wrong) didn't even use GDF11 for the tests and instead just used parabiosis and then measured "GDF11" in the circulation - in other words that paper is at this point - useless.

 

http://www.ncbi.nlm....les/PMC3677132/

 

Their next paper http://www.ncbi.nlm....PMC4104429/#R13

 

is more intriguing. The conclusion they reached after some in vitro experiments was that GDF11 unlike Myostatin can actually spur proliferation instead of inhibiting it ... but that's the thing, there's papers and not just one or two - I can't get a definitive number because I'll have to start reading all the GDF11 and related proteins papers one by one, but it's a sizable number of papers in complete disagreement with that observation - which is why Conboy wrote that long paragraph about GDF11 abdicating the throne etc.

 

There are other observations in the second paper. But it's questionable if they're related to regeneration and aging.

 

"GDF11 diminishes with age" was their big argument.

[corb]

Let's look at a recent paper on GDF11. It's from 3 days ago. Fresh off the press if you will.

 

 

Treatment with rGDF11 does not improve the dystrophic muscle pathology of mdx mice

Abstract
Background

Duchenne muscular dystrophy (DMD) is an inherited lethal muscle wasting disease characterized by cycles of degeneration and regeneration, with no effective therapy. Growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily and myostatin homologous, has been reported to have the capacity to reverse age-related skeletal muscle loss. These initial findings led us to investigate the ability of GDF11 to promote regeneration in the context of muscular dystrophy and determine whether it could be a candidate to slow down or reverse the disease progression in DMD.
Results

Here, we delivered recombinant GDF11 (rGDF11) to dystrophin-deficient mice using the intra-peritoneal route for 30 days and evaluated histology and function in both steady-state and cardiotoxin-injured muscles. Our data confirmed that treatment with rGDF11 resulted in elevated levels of this factor in the circulation. However, this had no effect on muscle contractility nor on muscle histology. Moreover, no difference was found in the number of regenerating myofibers displaying centrally located nuclei. On the other hand, we did observe increased collagen content, which denotes fibrosis, in the muscles of rGDF11-treated dystrophic mice.
Conclusions

Taken together, our findings indicate no beneficial effect of treating dystrophic mice with rGDF11 and raise caution to a potential harmful effect, as shown by the pro-fibrotic outcome.

The role of GDF11 in skeletal muscle regeneration has been controversial [8, 12, 15, 18].

 

While the previous report by Sinha et al. demonstrated that systemic injection of rGDF11 reverses age-related

dysfunction in the skeletal muscle [5], more recent studies, published while our study was in progress, contradict

this rejuvenating effect [15, 16]. In fact, the latter agree with previous publications describing GDF11 as a negative

regulator of myogenesis [17, 18], similar to its homologue, myostatin. Two recent publications by Egerman et al.

[15] and Rodgers and Eldridge [16] reported that some of the assays previously used to detect GDF11 [5] were not
specific, and that GDF11 has an inhibitory effect on muscle regeneration inhibition and that levels of GDF11
actually increase with age. In response to this, Poggioli et al. have recently reported that the apparent age dependent
increase in GDF11 levels, reported by Egerman et al. [15], is due to cross reactivity of the anti-GDF11 antibody
with immunoglobulin, which is known to increase with age [19]

 

Despite this controversy in the activity of GDF11 in the context of aging, we addressed here whether GDF11
would have the ability to ameliorate the muscle wasting phenotype in the context of muscular dystrophy, by pro-
moting muscle regeneration. Although daily doses of GDF11 treatment for 1 month resulted in elevated levels
of this factor in the plasma, we were not able to detect any beneficial effect on the histology or strength in the
muscles of treated dystrophic mice. We did not observe differences in terms of numbers of regenerating centrally
nucleated myofibers. In contrast, we did observe an increase of collagen content, which denotes fibrosis, in the
TA muscle of rGDF11-treated dystrophic mice compared to vehicle-injected controls

 

http://skeletalmuscl...3395-016-0092-8

 

 

Another good paper http://www.ncbi.nlm....les/PMC4858180/

 

Overexpression of LTBP4 protein was associated with increased muscle mass and proportionally increased strength compared to age-matched controls. In order to assess the effects of LTBP4 in muscular dystrophy, LTBP4 overexpressing mice were bred to mdx mice, a model of Duchenne muscular dystrophy. In this model, increased LTBP4 led to greater muscle mass with proportionally increased strength, and decreased fibrosis. The increase in muscle mass and reduction in fibrosis were similar to what occurs when myostatin, a related TGFβ family member and negative regulator of muscle mass, was deleted in mdx mice.

 

...

 

We found that LTBP4 also binds GDF11. GDF11 has received attention for its role in the aging heart and muscle [9, 38]. The current study investigates the role of LTBP4 overexpression in a model of muscular dystrophy. Because LTBP4 binds GDF11 in vitro, it is possible that muscle specific LTBP4 overexpression could alter sarcopenia or other aging related phenotypes. The current studies were not carried out of sufficient duration to draw any conclusions on aging-related phenotypes in mice. Additionally it may be necessary to express LTBP4 outside of skeletal muscle to alter aging. It has been suggested that GDF11 levels decline with age and that supplementation may be beneficial. However, other groups have not found a decline of GDF11 with age [10, 39]. The similarity between myostatin and GDF11 is striking, especially in their active domains where there is near complete identity. The capacity to distinguish these moieties based on binding partners, including antibodies or other protein-protein interactions is challenging given the similarity between GDF11 and myostatin. Therefore the significance of LTBP4 binding to GDF11 is not entirely clear. We used RNA sequencing to estimate the relative abundance of GDF11 and myostatin, and this method may not reflect protein levels. Nonetheless, a near 10:1 ratio of myostatin to GDF11 mRNA levels suggests that myostatin may predominant in muscle and that LTBP4 exerts its effect more through myostatin rather than GDF11.

 

 

 

 

[alc]

 Wager not Walker

 

... and that explains why you are confused with many things, and just rush to post all over the places, without understanding the fundamentals.

 

[mikey]

1. "Walker experiments" ? in other of your posts you keep repeating same thing "Walker experiments" - can you post some links to these? (I have a feeling that you are confused and mix the name with Amy Wagers ...)

 

2. "telomere therapy is found to be meaningless (something I strongly suspect will happen)" = yes, they already found + proven that ... lol

That is why recent study by Maria Blasco reinforces the TPE-OLD process.

So stay calm, these guys like: Maria Blasco/CNIO, Jerry Shay, Michael Fossel, George Church, etc. they  just like to waste their time. None of them are serious, there is only ONE group that is serious.

 

Please provide the citation for Maria Blasco's study.

 

Thank you!