Human GDF11 Does Not Decline With Age
Researchers have in the past couple of years shown that GDF11 levels decline with age in mice, and that restoring youthful GDF11 in old mice improves numerous measures of health. The mechanism involved may be increased stem cell activity. There has been some debate over whether the teams involved are in fact measuring what they think they are measuring, however. New human data in the research noted here today muddies the water some more, though these researchers are also claiming an improvement in the approach to measurement of GDF11 levels. This suggests that either mice and humans are different in this aspect of aging, or that the issues in prior methods of measurement were more prevalent than thought, or both. The outcome of improved health in aged mice following introduction of additional GDF11 isn't disputed, so it will be interesting to see how these various results are reconciled:
Researchers have developed an accurate way to measure a circulating factor, called GDF11, to better understand its potential impact on the aging process. They found that GDF11 levels do not decline with chronological age, but are associated with signs of advanced biological age, including chronic disease, frailty and greater operative risk in older adults with cardiovascular disease. "Aging is the primary risk factor for the majority of chronic diseases, so it is critical to identify and understand the biomarkers, or indicators, in the body that are linked to this process. The role of GDF11 as a biomarker of aging and its association with age-related conditions has been largely contradictory, in part, because of how difficult it has been to measure. We have developed a new way to measure GDF11 that is accurate and effective."
A challenge of previous measurements was differentiating between the circulating levels of GDF11 and those of a highly-related protein, myostatin. To overcome this, researchers developed an extremely precise assay that can distinguish between unique amino acid sequence features, or "fingerprints" of GDF11 and myostatin. Using this platform, researchers compared age-associated changes in GDF11 and myostatin in healthy men and women between 20 and 94 years old. They discovered that although myostatin is higher in younger men than younger women and declines in healthy men throughout aging, GDF11 levels do not differ between sexes nor decline throughout aging. In an independent cohort of older individuals with severe aortic stenosis, researchers found that those with higher GDF11 levels were more likely to be frail and have diabetes or prior cardiac conditions. Following valve replacement surgery, increased GDF11 was associated with a higher prevalence of re-hospitalization and multiple adverse events.
This confirms my suspicions that we are indeed very far from reversing aging in humans. Mice are a lot different from people, and whatever advancements in understanding we've made with mice will not necessarily carry over to humans. So far, nothing has been demonstrated to work in human patients. It seems we still have no idea what we're doing.
You have no idea what you're saying. Please put your head back in the dirt.
A great many interventions that show promise in anti-aging research, including those involving hormones, seem to work by affecting stem cell activity. If we can affect stem cell activity directly (through stem cell transplants or other means) then we should be able to replicate many of the positive effects of those interventions. Thankfully many researchers are working on stem cells. The important question is of course how much lifespan extension will be brought about by stem cell therapies? Years or decades? Hopefully enough to get many of us to advanced nanotechnology.
Dear MissKaioshin, I really like your witty remarks on the subject of the blog. It is evident that you are well versed in many ways. Could you apply in addition to criticism some ideas about how and in what way to carry out research in order to achieve progress in the understanding of aging and which road to take to defeat aging. Thank you in advance.
Hi there !
''A challenge of previous measurements was differentiating between the circulating levels of GDF11 and those of a highly-related protein, myostatin. To overcome this, researchers developed an extremely precise assay that can distinguish between unique amino acid sequence features, or "fingerprints" of GDF11 and myostatin. Using this platform, researchers compared age-associated changes in GDF11 and myostatin in healthy men and women between 20 and 94 years old. They discovered that although myostatin is higher in younger men than younger women and declines in healthy men throughout aging, GDF11 levels do not differ between sexes nor decline throughout aging. In an independent cohort of older individuals with severe aortic stenosis, researchers found that those with higher GDF11 levels were more likely to be frail and have diabetes or prior cardiac conditions. Following valve replacement surgery, increased GDF11 was associated with a higher prevalence of re-hospitalization and multiple adverse events. ''
I had a feeling there was more to that growth differentiation factor than being a youth rejuvenator in mice through differentiation and Transformation.
Growth, as with IGF, is a double-edged sword; you need some but in basal lowest quantity possible because it works on
good and bad mechanisms. Growth differentiation (11, GDF11)) is even more tricky and double-edged; cell differentiation is needed for cell maturation, growth and tissue formation; but there bad spin to it, is that to much activates a cascade of remodelling.
GDF11, in mice, reduces heart hyperthrophy through parabiosis; but in humans, that could be a different story and GDF11 activates TGF-beta (transforming growth factor); which is responsible for pathologic remodelling in diseases (such as cardiac fibrosis and, ironically, hypertrophy. I would wager that GDF11 in mice increases myostatin; thus reverting cardiac remodelling by GDF11, alone);
Myostatin (called growth differentiation factor 8, GDF-8) drops with age in humans and its role thus becomes absent (that of inhibiting muscle cell growth and differentiation). As such, GDF-11's weight becomes prominent (it is not inhibited anymore by myostatin being lost. Myostatin is also a double-edged sword as studies showed that myostatin inhibition contributes to improved cardiac function - after a heart failure - but before - having a heart failure, myostatin itself is good and, prevents one.)
as GDF-11's weight/impact grows uninhibited by myostatin : this creates excessive transformation, remodelling, differentiation growth-dependent; creating pathological states and illegit pathological organ remodelling/transformation.
That they say diabetes and older states have higher GDF-11, now would not surprise me, because diabetes people have sky-rocket levels of insulin or total lack of, and high blood glucose; which all activate IGF-1 receptors excessively; which they activate remodelling/transforming growth cascade -> IGF skeletal muscle formation/differentiation through GFD-11 -> vascular growth and remodelling VEGF, skin fibroblast hyperproliferation FGF-1 and epithelial growth factor (fibroblast contributing to fibrosis) -> hyperthrophy/fibrosis/pathological remodelled states..this is yet again a 'response' to compensate for skeletal muscle loss
and sarcopenia (IGF is a survival signal, and it signals to GDF, VEGF, GFs to make sure growth does not stop, when cells and tissue growth stops it can be as devastating - there is a middle ground balance that must be kept in check between growth/differentiation (GDF/IGF) and inhibition of such (myostatin)) to make sure organs/tissues relatively stay the same despite 'renewing' themselves through cell cycling/division/replacement/differentiation; growth allows creating of new muscle tissue but excessive growth *transformation* and growth differentiating - remodels things not in the best interest as our organs must maintain their structures; when they are remodelled (aka transformed), they are 'whack' and don't function well anymore as they are a 'transformed (mutant) version' of their former self. It makes make think of scarriffication which is the perfect example of FGF, GDF, IGF, EGF, fibrotic tissue 'remodelling' of wound...that is 'ok' to fill in the wound but is not the 'skin' as it was anymore (like a baby that after a wound injury heals perfectly to the skin as it was, no scarrification, no transforming remodelling).
Tranforming/differentiation is, like hormones IGFs, risky 2-faced terrain and associated with so many pathologies (fibrosis, hypertrophy, cancer, diabetes, alzh's, etc); but it is also a survival signal to remodel (remodelling can be good and slow aging, as seen with continuous brain tissue plasticizing/neuronal remodelling during puberty, seen in the naked mole rat brain protracted late puberty).
Lack of myostatin results in excessive muscle growth but impaired force generation
1. http://www.pnas.org/content/104/6/1835.long
Myostatin inhibition by a follistatin-derived peptide ameliorates the pathophysiology of muscular dystrophy model mice
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859604/
Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure
3. http://www.ncbi.nlm.nih.gov/pubmed/20065166
Myostatin inhibition after experimental heart failure improves cardiac function
4. http://content.onlinejacc.org/data/Journals/JAC/929967/07671.pdf
Myostatin Is Elevated in Congenital Heart Disease and After Mechanical Unloading
5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172210/
Myostatin Regulates Energy Homeostasis in the Heart and Prevents Heart Failure
6. http://circres.ahajournals.org/content/115/2/296.full
Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy
7. http://www.ncbi.nlm.nih.gov/pubmed/23663781
Good joke, Dmitry :D
Dmitry,
She wouldn't be able to do that because she's an internet layman without a scientific background that purely goes by what "actual scientists" say, and disregards anything that even resembles something positive. Also, why would she do that, when she can just go over to reddit with her magic 8 ball, and make proclamations that every medical breakthrough is nothing more than hype. Like this gem:
"Unfortunately there are still many who still expect to live for centuries in good health, not understanding that all of the "big breakthroughs" that they read about are nothing more than hype. They're in for a rude awakening in a few decades when these wondrous "breakthroughs" haven't materialized and are nowhere in sight, while they themselves have grown older, sicker, and have only death to look forward to.
Don't be those folks. Look at what the actual scientists are saying about biotechnology, regenerative medicine, longevity science, and all that stuff. They all say it's a very long way off. Stem cell science is still in its infancy. Gene therapies are still in their infancy. Medical nanobots are nowhere in sight, and may very well be impossible due to Brownian motion. Mind uploading is sheer fantasy. These are the facts.
So yeah, no extended lifespans, no turning the aging clock backward, no turning ourselves into immortal cyborgs, no uploading ourselves into cyber-heaven for eternity. Not in our lifetimes, not for those of us alive today. We will physically age and will die in our 70s, 80s, or 90s, assuming something doesn't kill us earlier than that. A few of us may live beyond 100, but will still surely die before we're 120. No one has ever lived much longer than 120. "
She sure seems to definitively know more than everyone else on this topic... all without working in science. Because "facts", and "actual scientists" say so.
And yet us researchers are busy making progress. I think they depressed I just wish they would take their cereal box science somewhere else. Can we please ban the ip reason?
If she gets banned this becomes a totalitarian, repressive, intolerant site, which no one wants. Why don't we just ignore her completely or use Dmitry's strategy? If no one even acknowledges her existence, the idiocy of her comments will automatically jump into the foreground. If we ask her to enlighten us with her superior scientific knowledge... well, what is she gonna say? These really are the only ways to deal with internet trolls. Anything else and we are unwittingly feeding them.
Just stop taking the bait already.
While MissKaioshin's claim that most scientists don't believe that immortality is around the corner is technically correct, it's misleading to assume that they have better crystal balls than anyone else. Scientists are mostly specialists which don't necessarily have better knowledge about the future of different biomedical fields than motivated and widely-read laypeople. It gets worse: with a few exceptions, scientists love to mess with metabolism to try to prevent or cure age-related disease, an approach which is unlikely to ever work well, and ignore or are ignorant of potentially much better approaches like SENS. This state of affairs leads to news that's mostly about "breakthroughs" which use MWM rather than SENS approaches and on closer examination aren't all that impressive or can't be applied to humans. The real breakthroughs are either ignored or lumped in with the MWM hype. So, it shouldn't be surprising that there's so much cynicism out there about eliminating aging any time soon.
Florin Clapa:
I dont understand; why wouldn't scientists have better knowledge about the future of their fields than laypeople? Just because they're specialists? I don't think I agree with that. Scientists understand their field far better than laypeople. They have firsthand knowledge of what's going on at the cutting-edge, and what's feasible in the near term. Laypeople don't. So I think the predictions and opinions of scientists should be believed over those of laypeople.
How could a heart disease researcher know anything about whether curing aging is possible, for instance? A layperson that's familiar with SENS and the latest SENS research could be able to make far more informed predictions about what's feasible regarding ending aging. And, as I mentioned before, even specialists will often only be familiar with approaches that are not cutting edge at all—just variations on messing with metabolism.
Florin, maybe you should point out to the lady that - you are in fact - a scientist.
Or maybe not, she is ignoring the fact scientists are doing all of the anti aging research to begin with. A laugh and a half.
Although I'm very familiar with SENS research and with most of the age-related disease research projects which some governments and private organizations fund (I've looked at thousands of such projects and read hundreds of the most interesting abstracts except for projects related to stem cell, cancer, and dementia research), I'm a well-informed layperson, not a scientist. But even if I were a scientist, that wouldn't necessarily make my opinions about aging any more valid than a well-informed layperson's. When it comes to aging research, you can't take the lazy way out and appeal to authority; you'll have to do your own homework and verify the logic and evidence behind whatever relevant expert opinion you're listening to.
Florin is right. The appeal to authority is inherently worthless. If an idiot says 2 + 2 = 4, they're right. If Einstein says 2 + 2 = 5, he's wrong (unless he means something different by it than what we're understanding).
This does nt mean that gdf11 causes frailty or adverse conditions. It may be just the other way around: *because* the body sensed a damage it reacts with an increase of gdf11