Investigating Mechanisms of Increased Muscle Strength Following Exercise
Mapping the regulation of improved muscle strength resulting from exercise may lead to interventions that increase or mimic these beneficial effects of exercise. Here, researchers report on a part of their investigation of proteins involved in regulating the response to exercise. They do not show that the new regulatory protein discovered in their work can be manipulated to enhance the effects of exercise on muscle strength, but they do show that it is important by removing it in mice to produce the outcome of greatly reduced muscle function.
Exercise induces signaling networks to improve muscle function and confer health benefits. To identify divergent and common signaling networks during and after different exercise modalities, we performed a phosphoproteomic analysis of human skeletal muscle from a cross-over intervention of endurance, sprint, and resistance exercise. This identified 5,486 phosphosites regulated during or after at least one type of exercise modality and only 420 core phosphosites common to all exercise.
One of these core phosphosites was S67 on the uncharacterized protein C18ORF25, which we validated as an AMPK substrate. Mice lacking C18ORF25 have reduced skeletal muscle fiber size, exercise capacity, and muscle contractile function, and this was associated with reduced phosphorylation of contractile and Ca2+ handling proteins. Expression of C18ORF25 S66/67D phospho-mimetic reversed the decreased muscle force production. This work defines the divergent and canonical exercise phosphoproteome across different modalities and identifies C18ORF25 as a regulator of exercise signaling and muscle function.
I like that this site appears to be embracing exercise or at least its unique and remarkable contribution to health, if not exactly longevity, in its articles (and especially those methods for monitoring and measuring such) . Of course, we should likely not idolize gym rats or others who spend 20+ hours a week in a gym as the 'path' to go forward. That being said, recognizing the 'ideal healthy' individual at each age range, naturally, in the sense using nutrition and fitness and perhaps, genetics, would go along way in establishing a baseline to understanding, maintaining, and improving the possible interventions to allowing people to meet their chosen level of functionality over their chosen length of existence -- likely at some future cost in time, money, and other sacrifices to life extension therapies. Perhaps, even more important than clocks, establishing a configuration or range of metrics of the ideal health may allow monitoring of deviations well before they become pathologies. As may have been noticed in previous comments, understanding the approaches of elite athlete training coaches to monitor and optimize their subject may provide assistance in 'coaching' us to better health and eventually, longevity.
[offtop]
https://bigthink.com/health/crispr-cholesterol-gene-therapy/
CRISPR cure for high cholesterol enters first human trial.
At least one person has already taken the plunge, receiving a dose in Verve's trial, which will involve approximately 40 adults with "heterozygous familial hypercholesterolemia" (HeFH)
@Reason
how would you compare such a treatment against your Cholesterol Degradation Platform ?
@Cuberat: Very different. This is just another way to lower blood cholesterol, which can always only have limited impact on mortality. The advance is it is a one time thing rather than a lifetime of treatments.
Hey everyone, I know Reason and others have mentioned this off hand in numerous posts, and this is going to be grumpy and probably offensive... but:
why does it take so long to run medical experiments?
I would think, for example, D+Q tests to measure effectiveness and safety in humans, should take about $100k and 6mo to complete (with maybe some 2 year followups or something). Why is the real answer like 5+ years?!
Also, I remember about a year ago seeing an online presentation where Reason talked about his company and their plans to use engineered macrophages to clear cholesterol. It sounded awesome... what happened? How hard can it be to jab some people with the medicine and see what happens?
Underdog Pharmacuticals (though I think they changed their name?)... drill some holes in a plate around the nose and help the brain drain its waste products and see if it helps stop Alzheimers... how hard can it be? The surgery sounded somewhat simple... where are the results?
Is it that hard to find suitable candidates who are willing to undergo the treatment? Are the treatments that expensive? Is it that expensive to have some medical professionals administer the medicine/treatments in a professional facility? Really... what's the big deal?
Is the US just the wrong place to try these things? I would happily help crowdfund these projects... for literally nothing other than to see them actually make progress.
Any thoughts?
Again, I'm sorry I'm ranting here... but it really comes from ignorance. Please, enlighten me.
Very interesting Cuberat. But I would not want to be one of the first 10,000 humans to get that injection
Gregory, this article may give us some hope for the future. I think the answer to your question has been " red tape"
https://www.scientificamerican.com/article/covid-showed-how-trials-for-new-drugs-could-be-faster-and-better1/
Cuberat: LDL Cholesterol is probably necessary for some biochemistry. I suggest fighting the negative effects with natural, live apple cider vinegar. Bragg's works for me.
Just want to say the injected SARS2 gene Therapies have done more to ruin my faith in regulatory competence than anything else.
Although the public have already been fleeced to purchase the injections, so no choices there.