Suspicious "restorative" proteins

In the past, the explanation of "the blood of young mice can recover muscles" has been challenged Some laboratories have come to the opposite conclusion That's an incredible observation: after connecting the circulatory system of a young mouse and an old mouse, the old mouse seems to have recovered This effect was first discovered in the 1950s From then on to 2015, several research labs are eager to find the molecular substances that lead to this effect, in order to use them to slow down or even reverse human aging One of the labs was particularly successful: they found a protein called Gdf11 in the blood of young mice A research team at Harvard University has published several highly opinionated papers on this issue (two of which were published in last year's Science), saying that the protein has decreased in older animals, which makes it impossible to reconstruct their muscles, brain and heart However, just this week (May 22, 2015), according to a team from the Novartis institutes for biomedical research in Cambridge, Massachusetts, their results challenged the authority of Gdf11's resilience In fact, the Novartis team does not question the idea that the blood of young mice can make older mice recover, but believes that the Harvard research team is wrong in explaining this phenomenon Their paper, published in cell metabolism, questions the Harvard team's use of earlier findings for analysis and suggests that Gdf11 actually inhibits muscle regeneration Michael Rudnicki from Ottawa Hospital Research Institute, who participated in the affiliated review of the paper, said frankly that the whole research premise of Harvard research group was not correct Others are much more cautious, but agree that the new study has weakened some of the original claims about Gdf11 For example, biologist Thomas rando of Stanford University in Palo Alto, California, believes that Gdf11 does not decline with the age of animals The Harvard team is not weak either Its stem cell biologist Amy Wagers, who has undertaken most of the original research, believes that Novartis' data on the level of Gdf11 alone is not convincing, and says that they still firmly believe that with the growth of animals' age, at least one form of Gdf11 decreases in the blood, while for muscle health, maintaining the level of Gdf11 within the appropriate physiological range is crucial Therefore, wagers, as a postdoctoral fellow, cooperated with rando et al To explore various ways to influence the aging process by connecting the circulatory system of mice of different ages (this process is called heterosymbiosis or symbiosis) (Science, 12 September 2014, p.1234) In 2013, her team collaborated with Richard Lee, a cardiologist at brightam and women's hospital Hospital's laboratory, published in cell, proposed that: with the growth of mice's age, the level of Gdf11 in their blood decreased correspondingly, and they restored the level of Gdf11 in mice by injection (similar to the heterosymbiosis of young mouse and old mouse), so as to partially reverse the age-related cardiac hypertrophy Last year, wagers and his collaborators, including Lee and Lee Rubin, a Harvard neuroscientist, published an article in science, suggesting that Gdf11 can also provide nutrition for the cerebral vessels of older mice, promote the growth of nerve cells, and improve their sense of smell In their second science paper, wagers and Lee reported that Gdf11 stimulated the recovery of damaged muscles in older mice, because they achieved better results in strength and running tests after receiving Gdf11 However, some experts are puzzled by this paper on muscle recovery, because Gdf11 is a "close relative" of myostatin, a protein that can control muscle growth, which has been studied in depth before: animals and humans without myostatin can grow large bulging muscles, and the substance is excessive It can also inhibit muscle regeneration, so why does a protein that is very similar to it show different effects? David glass from Novartis center is one of the doubters who helped develop a muscle somatostatin blocker for the treatment of muscle atrophy His team tested Gdf11 levels in rats using two methods wagers used - proteomics and commercial antibody analysis - but found that they could not distinguish Gdf11 from myostatin As a result, they used a more specific test method, and found that the level of Gdf11 in the blood of rats and humans did have an upward trend with the increase of age, and the level of Gdf11 mRNA in the muscle of rats also increased with the increase of age The Novartis team also tested the effect of Gdf11 on muscle regeneration They did a common experiment: they gave Gdf11 to a young mouse and then injured its leg muscles with snake venom As a result, the regeneration of mouse muscle was weakened As a result, glass says, their conclusion is that Gdf11 appears to cause muscle damage However, wagers still insists that his data is correct Her team used another antibody that can distinguish Gdf11 from myostatin in their science paper and found that the level of Gdf11 decreased with the age of mice, she said And, she said, there was no comparison between glass's group's injury test and her study, because the other side used mice, and the dose of Gdf11 was three times higher (so glass only completed part of the experiment, because he did not see any effect of wagers in mass production in older mice) Wagers pointed out that, in fact, the signaling pathway of Gdf11 has "well-known dose sensitivity", and different effects will appear in different situations of low dose and high dose In addition, the Novartis group's muscle regeneration test is not comparable to her test - the Harvard group used frostbitten tissue to cause muscle injury, which is unlikely to kill the muscle stem cells necessary for muscle regeneration like toxins In addition, wagers said that the new data her team obtained would prove that "there is a very convincing biological explanation for this obvious contradiction." Lee, one of her collaborators, agreed But Rubin, the other, is more cautious: it's obvious that we should pay attention to this report So while Novartis's results failed to challenge the wagers team's renewed assertion that Gdf11 is good for the brain, Rubin, who led the study, said they were designing a series of experiments to convince themselves that everything they saw in the brains of experimental mice was true Others seem to be more calm about this One of them, Se Jin Lee, a molecular biologist from Johns Hopkins University in Baltimore, Maryland, who specializes in muscle somatostatin, said that even if Novartis' new findings were correct, there might be at least no way to refute some of the benefits reported by wagers and others He pointed out that the internal effect of Gdf11 is likely to be complex, so "there are still many problems to be solved" All in all, it remains to be seen.