MOTS-c is one of several recently identified hormones known to mimic the effects of exercise. However, MOTS-c is unique because it is encoded in the small genome of mitochondria rather than the larger genome in a cell’s nucleus. This opens up a whole new genome to target for new interventions, says Lee and researchers at USC. His subsequent studies showed how mitochondrial-encoded MOTS-c instructs proteins to interact with the nuclear genome and plays important roles in regulating cell metabolism and stress responses.
Injections of MOTS-c affected mice of different ages by measuring physical capacity and performance in young (2 months), middle-aged (12 months), and old (22 months) mice. Mice of all ages who had received MOTS-c treatment fared significantly better than untreated mice of the same age.
The human equivalent of 65 and above doubled their running capacity on the treadmill and outperformed human equivalent middle-age mice.
In muscle cells, levels of MOTS-c significantly increased nearly 12-fold after exercise and remained partially elevated after a four-hour rest, while MOTS-c levels in blood plasma also increased by approximately 50% during and after exercise and then returned to baseline after the rest period. The findings suggest that the exercise itself induced the expression of the mitochondrial-encoded regulatory peptides.
Mitochondria are strongly implicated in aging at multiple levels and MOTS-c may contribute to longevity by promoting cellular homeostasis. Here, we present evidence that the mitochondrial genome encodes for instructions to maintain physical capacity (i.e. performance and metabolism) during aging and thereby increase healthspan. MOTS-c treatment initiated in late-life, proximal to the age at which the lifespan curve rapidly descends for C57BL/6N mice, significantly delayed the onset of age-related physical disabilities, suggesting “compression of morbidity” in later life66. Interestingly, an exceptionally long-lived Japanese population harbors a mitochondrial DNA (mtDNA) SNP that yields a functional variant of MOTS-c.
The study shows that exogenously treated MOTS-c enters the nucleus and regulates nuclear gene expression, including those involved in heat shock response and metabolism. Thus, age-related gene networks are comprised of integrated factors encoded by both genomes, which entails a bi-genomic basis for the evolution of aging. Although the detailed molecular mechanism(s) underlying the functions of MOTS-c is an active field of research we provide a proof-of-principlevstudy that realizes the mitochondrial genome as a source for instructions that can regulate physical capacity and healthy aging.
Nature Communications – MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
Healthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate aging are unknown. Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice. MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis, (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress. We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Our data indicate that aging is regulated by genes encoded in both of our co-evolved mitochondrial and nuclear genomes.
SOURCES- Nature Communications, USC
Written By Brian Wang, Nextbigfuture.com
Brian Wang is a Futurist Thought Leader and a popular Science blogger with 1 million readers per month. His blog Nextbigfuture.com is ranked #1 Science News Blog. It covers many disruptive technology and trends including Space, Robotics, Artificial Intelligence, Medicine, Anti-aging Biotechnology, and Nanotechnology.
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25 thoughts on “Exercise Protein Lets 65 Year Old Human Equivalent Mice Outperform Middle Age Mice”
Too much CD38 inhibition leads to autistic like behavior.
But I don't want to have solid red eyes.
The last time I tried Nicotinamide Riboside (NR), my blood sugar went up, causing me to go from pre-diabetes to full-blown diabetes. So I stopped taking the NR, and my blood sugar went back down, but I've stayed away from that stuff since then.
I won't try it again until there's a better treatment for diabetes. Fortunately, that may be in the offing:
"Personally, I expect that most cells have at least some healthy mitochondria anyway"
Kind of tautologically true: If most of your cells were lacking healthy mitochondria, you'd be dead. The problem is that it doesn't take a lot of unhealthy but living cells to really degrade your health.
When exercising, absolutely. Just normal day-to-day living, I really didn't notice any effect, but when exercising strenuously with weights, I seem to recover much faster and have much more energy to push for that extra pound, you know?
That said, it's really hard to tell how much of this was psychosomatic or a real effect.
Did you notice any results?
I've tried it.
Not really related but I saw this encouraging story: https://www.nbcnews.com/science/science-news/german-scientists-make-paralyzed-mice-walk-rcna235
Then there is plasmapheresis. That really is like changing the oil. It takes the crud out of your blood that has been accumulating because your organs haven't been removing it. They replace it with albumin and a saline solution.
Fisetin + Quersitin I think work well together for senescent cell clearance. I also include Piper Longum. When I do my near fasts (<10% calories from protein, and below 700 calories total for 3+ days), I take these senolytics. And I have started taking a modest amount of Fisetin daily.
I am also trying to minimize the intake and creation of AGEs (Advanced Glycation End products) https://en.wikipedia.org/wiki/Advanced_glycation_end-product
The kidneys can remove most of this as long as they are not overwhelmed (which I think is somewhat common as there are so many sources of processed food), but one kind it can't, and that builds up in aging: https://en.wikipedia.org/wiki/Glucosepane
The accumulation of glucosepane contributes tissue stiffening, and compromised function as a result. It is responsible for much of the arteriosclerosis, joint stiffening and skin wrinkling that accompanies aging.
Some supplements can reduce the creation of AGEs, but there is nothing on the market known that can remove glucosepane…yet.
And I don't think antioxidants are totally useless. They may not dramatically reduce aging, but I think they help, and some of those reduce the formation of AGEs.
I wish there was a dietary guide that specifically measures glucosepane, but all I have seen is a more general AGE measurement of a fraction of common foods:
And it is starting to look dated; its missing a lot of new foods that have become popular.
I am an investor, so ignore this if you think that biases me…but I am telling it how I see it. This stuff works wonders on my muscle strains. They heal in half the time or less. It also helps with my bullet chess (1-minute for whole game). I seem to be a bit faster, especially when things are really flying at the end…and those moves seem to be better quality.
There are only about 30 or so people higher rated than me last I checked at ICC (Internet Chess Club).
I can't say I actually feel more energetic, more upbeat or anything. I don't think I am even physically any stronger.
I am not happy with the price of the Tru Niagen, either as an investor or a customer. I think they should lower the price. I think they would get a lot more customers if it was about 1/3 the current cost. And there is too much fancy packaging. It can't really cost that much to make this stuff. When this stuff is being used a lot, there is a greater likelihood that third parties will do more studies, and see what it is good for. Self-paid studies always invite doubt.
Like, an ion resistant nanoparticle coating that also helps transfer the mitochondrion through the plasma membrane? Could be possible.
In this article, they do something like that, but focusing specifically on the liver: https://www.sciencedaily.com/releases/2020/06/200625122732.htm
Personally, I expect that most cells have at least some healthy mitochondria anyway, and the real trick is getting rid of the bad ones (the healthy ones would then just reproduce to fill the gap).
This article talks about a method for that: https://www.sciencedaily.com/releases/2019/05/190515131741.htm
For this particular gene, I think that concept is now proven. Hell, apparently the gene doesn't even need to be expressed in the same cell for a positive effect. So a gene therapy migrating the gene into the nucleus would be useful even if only a small portion of cells got the edit.
I am a little concerned that allotopic expression might not be regulated in the same way, but if mere injections of the protein are so great, then I'm not sure it's important that it be tightly regulated by mitochondrial conditions.
Allotopic expression of mitochondrial genes may be a good solution.
The news for mice just gets better and better 🙂
Yes, I hope you're prepared to be ruled by our future trans-murine masters.
I'm fine with getting it in a needle. You get used to injections pretty fast once you need them. But you could do long term treatment by transplanting in encapsulated engineered cells to act as factories for this hormone.
Yet more confirmation that aging is mostly a mitochondrial disease. Fortunately, your mitochondria can be replaced, because they represent a self-reproducing population within the cells, so you only have to get one or two in to have an effect. So in theory you could genetically engineer them, and introduce the engineered mitochondria as a treatment.
Unfortunately, efficient mitochondrial transplantation in vivo is hard, because mitochondria are damaged by extra-cellular calcium ion levels. Could they also be engineered, or just treated, to be resistant to that?
We desperately need a good delivery mechanism for mitochondrial transplants, and for multiple diseases besides aging.
Humans are going backwards but we have super mice!
Well, now they have to do a new mice model test using x100 fold the normal dosis during a time test equivalent to 70 human years of continuous overdose to see that tumors or other lethal pathology arises and stops the develop. Déjà Vu. They don´t want long span life of "normal" citizens.
Both are cool. Less inflammation and better brain function, joined with stronger muscles can make old age much more bearable, and probably make you live longer (and making it worthy of living).
Meanwhile, in China:
"While NAD+ shows promising results in enhancing the seniors' life conditions, CD38 inhibition could be the next gold in anti-aging research."
When will some of these much-talked-about anti-aging developments actually translate into treatments available to the general public?
Exercise in a needle. Long dreamed of by people who want to make big dollars.
Exercise in a pill is where the real money is though.
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