Gene Therapy Doubled Strength and Reduces Fat

Gene therapy helped build significant muscle mass quickly and reduced the severity of osteoarthritis in the mice, even though they didn’t exercise more. The therapy also staved off obesity, even when the mice ate an extremely high-fat diet.

Science – Gene therapy for follistatin mitigates systemic metabolic inflammation and post-traumatic arthritis in high-fat diet–induced obesity

Even without additional exercise, and while continuing to eat a high-fat diet, the muscle mass of these “super mice” more than doubled, and their strength nearly doubled, too. The mice also had less cartilage damage related to osteoarthritis, lower numbers of inflammatory cells and proteins in their joints, fewer metabolic problems, and healthier hearts and blood vessels than littermates that did not receive the gene therapy. The mice also were significantly less sensitive to pain.

One worry was that some of the muscle growth prompted by the gene therapy might turn out to be harmful. The heart, for example, is a muscle, and a condition called cardiac hypertrophy, in which the heart’s walls thicken, is not a good thing. But in these mice, heart function actually improved, as did cardiovascular health in general.

Longer-term studies will be needed to determine the safety of this type of gene therapy. But, if safe, the strategy could be particularly beneficial for patients with conditions such as muscular dystrophy that make it difficult to build new muscle.

Abstract

Obesity-associated inflammation and loss of muscle function play critical roles in the development of osteoarthritis (OA); thus, therapies that target muscle tissue may provide novel approaches to restoring metabolic and biomechanical dysfunction associated with obesity. Follistatin (FST), a protein that binds myostatin and activin, may have the potential to enhance muscle formation while inhibiting inflammation. Here, we hypothesized that adeno-associated virus 9 (AAV9) delivery of FST enhances muscle formation and mitigates metabolic inflammation and knee OA caused by a high-fat diet in mice. AAV-mediated FST delivery exhibited decreased obesity-induced inflammatory adipokines and cytokines systemically and in the joint synovial fluid. Regardless of diet, mice receiving FST gene therapy were protected from post-traumatic OA and bone remodeling induced by joint injury. Together, these findings suggest that FST gene therapy may provide a multifactorial therapeutic approach for injury-induced OA and metabolic inflammation in obesity.

SOURCES- University of Washington, Science
Written By Brian Wang, Nextbigfuture.com

43 thoughts on “Gene Therapy Doubled Strength and Reduces Fat”

  1. Why would they run when they could easily overpower the thinner people. BTW, skinny people make for lousy eating, not enough fat.

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  2. The same gene tweaks that will maximize space colonists ability to hold onto muscle and bone strength may counter obesity as the same time. that sounds productive.

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  3. If you’d like a bit of speculation you could ask why every single drug that grows muscle or reduces obesity since the 1930s has been banned.

    I’m not being deliberately vague here. I have no idea. But it’s intriguing.

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  4. Gene therapy might help with the debilitating effects of long duration space missions like muscle and bone atrophy.

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  5. Big gymnasts can make the same moves, they are just slower in the air and higher…which actually looks better. The reason the gymnasts are very small, especially the women, is that there is only so much room for tumbling runs. It also looks much better when on the uneven bars a girl can go around the higher bar without bending/minimally bending to keep from whacking the shorter bar. If they had a much larger mat for the floor exercise with say 3 different lines for different sizes of athlete, the taller athletes would have room to do the same elements. The men are much less limited because they have only one bar. Though that dang narrow bar hurts…should be wider 🙁 Landing on your upper arms on the parallel bars is also extremely brutal…probably should be banned. There is still blue on one of my arms, and I haven’t done it for a long time. No, I was never any good…just one semester in College. Strong but too heavy. And my lower body was stronger than my upper body…gymnastics, especially male gymnastics favors the other way. My best fit was rowing which deceptively is more leg and back.

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  6. You are going to have inefficiencies with the enzymes. They will move away from optimal. Maybe giving up 10% or 20% doesn’t mater. Maybe the body can adjust and make more enzymes to make up for the difference.
    The thing is…low iodine causes this, and there are many negative effects. https://www.healthline.com/nutrition/iodine-deficiency-symptoms#section6
    I think that is enough to question trying to lower temperature without actually changing the genetic coding of our enzymes.
    I suspect the only good way to achieve a lower temperature, short of genetic modification, is doing things to reduce inflammation. Inflammation can heat and cause all sorts of aging damage.
    But if your choice is a diet to reduce inflammation, I would also advocate minimizing AGEs (advanced glycation end products), and avoid plant toxin build up. That means not just eating the 20 foods they recommend or eating some 3 foods every day. You have to have variety in fruits, vegetables, and nuts. This is especially true in the modern era where there are toxic chemicals and elements in/on crops. And organic is not a ticket to low toxins. Any toxin naturally in the ground or in the plant is given a pass. Even if the toxin is not naturally at that level but they add it or amplified it by normal breeding methods, it would be given a pass.
    I think a better approach is supplements for inflammation: alpha-lipoic acid, salmon oil, curcumin, spirulina…
    And some adjustments to the diet…but less extreme.

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  7. Neanderthals had much smaller semicircular canals in their ears. That means their balance was likely much worse, which makes running at speed dangerous. They also lived in forests, where speed was dangerous. There is too much to run into, step on, or fail to see… There were animals you want to stay away from: https://www.smithsonianmag.com/smart-news/ancient-carnivores-had-taste-neanderthal-180955390/ They had shorter legs also reducing speed and likely endurance: “While modern humans have evolved gracile anatomies more adapted to long-distance running, Neanderthals were built for more intense bursts of action.” https://www.telegraph.co.uk/science/2018/04/05/neanderthals-capable-turbo-breathing-according-new-study-facial/
    Not an iron clad case, I admit. But you can see these patterns in modern athletes. Short fat legs are a clear disadvantage for long distance runners…sprinters too. Short limbs are good for wrestling and have advantages in leverage in lifting or moving heavy things. They also are less likely to break. Less likely to get frostbite. Easier to pull out of a bog or a mud hole.

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  8. That is a lot of topics to cover. Speed of body and mind are not limited by cold until reaching the freezing point of water. It is true that reptiles and insets are slower when cold, but that is just a result of the particular ATP generating enzymes they have and optimal temperatures of those enzymes…and other trade-offs. Cephalopods have very advanced brains and quick muscles that operate rapidly at near 0 deg C. They have more than double the neural synaptic genes for brain complexity. They have 168 Protocadherin genes. We have 70 which is more than anything outside of the cephalopods. That permits much higher neural efficiency. Fish/shark muscles can be rapid and powerful despite the temperature. They can do things you would think was beyond them like this: https://www.youtube.com/watch?v=8nEwte-x-iw
    Some fish can even swim upwards of 60 mph, possibly even 80 mph in short bursts according to line let out speeds when being caught.

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  9. There were a couple myostatin blocking agents being developed by big pharma as recently as 2019 that were dropped for unknown reasons. These drugs reversibly did the same thing that this irreversible gene therapy seems to be proposing to do. These drugs were being targeted to treat cachexia and wasting syndrome in older folks. The main side-effect you needed to look out for was cardiomegaly since blocking myostatin caused hypertrophy in ALL muscles. Seems like it was going to be the next big thing for juicers and tons of people would have bought and possible abused it. would have been good $$ if not unethical…wonder why they dropped it? Does big pharma have a conscience???

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  10. Legal practicalities only matter if you can detect it.
    So yes, if the winning sprinter turns out to have cheetah proteins in her leg muscles…

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  11. There are some suggestions below to reduce the size of humans. I think we should go the other way. Has anyone seen the alien movie with huge, pale, humans? Remember how the one they woke up teared Fassbender in half?

    OK, if it could be avoided being so pale and having a really bad temper, why not make humans 5 meters in height? And while you are at it, give them a life span of a few hundred years and an average IQ of 250. Any takers?

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  12. Reptiles are cold blooded so that is another strategy. They heat up using external sources so they use less energy. The price is less activity and a limitation to which environments they can populate. Successful it is, especially for reptiles like crocodiles and turtles using water environments. They have survived for 200+ million years and counting.

    Earth is a rather small place and evolution will do its thing also when life migrates out in the galaxy in the future. Astro-biologists are trying to predict what life can look like in vastly different environments. I remember one exercise/simulation where they reached the conclusion that the optimal design for a creature living in space and harsh environments would be something like Alien the xenomorph.

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  13. Interesting. I know that Neanderthals had more muscle, but could you provide a source to them being slower and/or less enduring?

    Also, aren’t mamals just smarter then reptiles? Could that be an explanation to the mammals dominating the fauna?

    How about intelligence. How does it scale with temperature? If the brain works slower at lower temperatures, would be worth the hassle of reducing the temperature? I mean, if your neurons fire the same number of times in you lifetime, regardless if you live “hot” or “cold” then presumably you have lived the same amount of subjective time, no?

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  14. Good reasoning overall, agree with 95%. Only with gymnast I think you are wrong. It’s the same story with any hip hop or pop music dancers. Why are they so short?

    For dancing the answer is obvious. The kinetic energy per unit of mass to do a movement scales as the square of the size. This means that increasing the body size of a dancer by 10% results in needing 21% more kinetic energy *per unit of weight* to complete the movement in the same time.

    This is why the shorter dancer is always going to be able to complete a turn faster, lift a leg faster etc than a tall dancer. And this is suitable for modern choreography that is based a lot on abrupt acceleration and fast movements.

    The gymnast, similarly, has to be able to complete flips in mid air. The same flip for a 20% taller person would require loading his/her body by 44% more kinetic energy per unit mass, or, taking longer to perform the flip. And, if the taller person would require 20% more time in air, this person would have to expend 44% more kinetic energy when jumping (per unit mass), so there would again be a penalty that scales with the square of the body dimensions.

    Short gymnasts are a product of physics, not discrimination…

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  15. I saw somewhere recently a review of methods designed to lower the human body temperature set point.

    Apparently you can do so by 3-5 degrees without tripping over any biochemistry changes that cause long term problems. After that you get enzymes not working as well and things like that which complicates matters hugely.

    3 degrees is apparently enough to see significant expected longevity changes (once again, one review I read, and I’m working on memory as I didn’t keep track of it).

    I’ll note that reduced body temp was one of the effects of calorie restriction, and the increased lifespan of calorie restriction was just about the amount you’d expect from the temperature change alone. So they speculated that maybe that was the mechanism. So you can eat to your heart’s content (errr… stomache’s content) providing you get the temp down some other way.

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  16. The psychological requirements for astronauts are pretty formidable. 130 IQ minimum (roughly 2.3% of people), calm in the face of danger, good memory, don’t require much sleep, never get upset, get along with people in tight spaces, not prone to cabin fever, not prone to space-sickness, not a klutz, mechanically inclined, inoffensive, clear in communication, excellent hearing and sight, psychologically rock stable, not irrationally optimistic or pessimistic, and pilots must be coordinated, able to remain conscious under high G-forces and have good reflexes.
    I think that is getting in the 1 in 100,000 territory or more scarce. For pilots maybe 1 in 500,000. They did have a height limitation early on. That has probably been relaxed. Seems like they are taller than they used to be. I don’t think your pygmy plan is going to find many candidates. There are approximately 600,000 African pygmies. Starting in infancy maybe? I think the advantages are just too trivial. You can make the rocket a little bigger. I think it is also psychologically devastating for any hardworking very bright person who wants to be an Astronaut, when the seats are chimp sized, and there is nothing they can do to become an astronaut. Even short people have gotten into the NBA. Talent, work ethic…doable. Tall gymnasts? Sadly no. I think that is artificial too. The floor exercise is too small. Equipment should be adjustable for size. But that is a different grumble.

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  17. Actually, the reptiles are very efficient using roughly 1/10 the calories of warm blooded mammals…yet everywhere you look…mammals.
    I think we will recapture some of that efficiency via genetic engineering someday. Reducing body temperature just has too many advantages: extreme long life, ability to hold breath longer, less food required, better likelihood of effective cryogenic suspension technology. Some fish, reptiles, insects, and other creatures already manage this: https://www.youtube.com/watch?v=YoIcPezoDyo
    Neanderthals had more muscle. We gave it up for speed/endurance, because we could as we had more effective kill at a distance technology bows, poison arrows, and dogs. It became more important to keep up with or track the animal you mortally wounded, rather than confronting it while it can still put up a fight and trying to end it before it could get away.

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  18. We already live in a world where we can bypass natural selection, with new technics rising exponentially that allows to deny death. Could this have major effects on the develop of our and other species? Like increasing the need for healthcare, more diseases with higher fatality rates (hmmmm), eventually choosing partners will be determined by how much money they invested on themselves to look perfect and healthy..
    Our genetics will be “weaker”

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  19. When the famine comes, only obese people will survive. And for those who don’t believe the famine will come I give you COVID.

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  20. easier said then done. Huge resources spent on trying to ‘clear’ cancerous cells to limited success over the decades just to live a normal life. Identify and target only those ‘senescent cell’ inflammation sources as the body becomes increasingly unable to self-clear is like trying to plug a dyke against a rising ocean. The body is fundamentally limited and fragile. Better to upload and/or switch out organs and/or provide substitute parts if you want to live past 110 and be walking past 100.

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  21. I think Heinlein was on the right track when he wrote about “rejuvenation clinics” where specialists applied a wide variety of therapies, including psychological, to bring their patients back to a youthful vigor. It won’t be any one thing, but many and each individual will require different remedies.

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  22. I see people whose skin color suggests recent ancestors living near the equator skiing on the trails near Calgary. Good clothing does wonders

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  23. I dunno I remember certain members of the Oakland Atheletics who through skill and doping (but mostly doping) could turn fly balls in to home runs.

    Then again I think that the pinnacle of athleticism is Joona Sotala.

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  24. I think it would be better to have more human-centric space environments than to change humans for space.

    More cargo capacity at lower cost helps launch more mass, and more mass allows more shielding, result in shorter trips (more fuel) and we can build bigger habitats with more mass.

    With more mass you can build rotating habitats that don’t degrade your bones, muscles and organs.

    In this way, we don’t change the definition of human, and we avoid creating splicers or sub-species that can’t live anywhere any other human can. Humans don’t really need other reason for division and contempt.
    .

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  25. Yep. The search for moral purity again causes unnecessary suffering, by infecting other areas and going beyond the original intent of the rules.

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  26. This would be very true at a hunter gatherer society level. It may also have implications in retaining heat in an ice age. We’ll just have to avoid those.

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  27. I am pretty sure that clearing senescent cells from their bodies will do far more. If you don’t clear the root cause then enhancements will likely not work.

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  28. When this gene therapy is perfected it will do wonders for old frail people by giving them more Independence and an improved quality of life.

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  29. Always looking for sources that show that exercising-type results (usually by exercising) not only mitigate ‘sedentary diseases’, but when expanded further, will increase health-span (if not directly, overall life span) and have a disproportionate benefit to all body systems (resistance and aerobic (and flexibility)):
    “…Ten Weeks of Resistance Training in 60-Year-Olds Doubles NAD+ Levels in Muscle Tissue… looking at the work presently taking place on improving metabolism in older individuals, whether by stress response upregulation, or by improving mitochondrial function… a useful resource when comparing exercise to the class of approaches that fairly directly increase levels of NAD+/NADH – molecules involved in mitochondrial function. A number of supplements and treatments are on the market or under development to increase NAD+ levels in older people, and an initial human trial has been published for nicotinamide riboside. In that trial, nicotinamide riboside supplementation boosted NAD+ by 60% or so in immune cells. NAD+ was more than doubled in muscle cells following ten weeks of resistance training, restoring levels in older people to that of collage-aged individuals….”

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  30. After the legal practicalities are worked out. We already have separate athletics for people with handicaps. No reason we can’t have separate “classic” games and modified games. It’s not like participants aren’t already ok trampling that taboo.

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  31. Pretty much.

    That “doping” concerns have set back efforts to treat sarcopenia is just one more reason I loath professional sports.

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  32. That reminds me of an idea my “interesting” uncle had a while back – that NASA should bring over a tribe of pygmies from Africa, and then train them to be astronauts.

    Anyways, I doubt the food thing would really be an issue; even plenty of developing countries are having obesity issues. And right now about 40% of the US corn crop gets turned into ethanol. That ethanol won’t be needed as we switch over to electric vehicles, so that leaves tons of reserve farmland.

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  33. Evolution has favored energy efficient life forms for a reason. Having a population of super strong, lean individuals will only work where there is a very good long term supply of food. If we want to be that way, it would be logical to also shrink down to half the size/length/weight. That will balance out things and decrease the resource usage everywhere.
    That would also be a very good thing for space exploration. Downsized astronauts (probably taikonauts) are much easier to accommodate and accelerate.

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  34. A new era of gene-doping will arrive which makes mere anabolic steroids look weak in comparison.

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