New research makes a case for exercise that promotes youth

Summary: Exercise has an epigenetic effect that promotes youth on aging organisms, a new study reports.

Source: University of Arkansas

A recent paper published in the Journal of Physiology deepened the case for the youth-promoting effects of exercise on aging organisms, based on previous work done with laboratory mice near the end of their natural lives that had access to a weighted exercise wheel.

The densely detailed paper, “A molecular signature defining exercise adaptation to aging and partial reprogramming in vivo in skeletal muscle,” lists a whopping 16 co-authors, six of whom are affiliated with the The of A.

The corresponding author is Kevin Murach, an assistant professor in the Department of Health, Human Performance and Recreation at the U of A, and the first author is Ronald G. Jones III, Ph.D. student in Murach’s Laboratory of Molecular Muscle Mass Regulation.

For this paper, the researchers compared aged mice that had access to a weighted exercise wheel with mice that underwent epigenetic reprogramming via the expression of Yamanaka factors.

The Yamanaka factors are four protein transcription factors (identified as Oct3/4, Sox2, Klf4 and c-Myc, often abbreviated OKSM) that can turn highly specified cells (such as a skin cell) into a stem cell, which is a younger and more adaptable state.

The Nobel Prize in Physiology or Medicine was awarded to Dr. Shinya Yamanaka for this discovery in 2012. In the correct dosages, inducing Yamanaka factors throughout the body in rodents can improve the distinctive signs of aging by mimicking adaptability which is common to younger people. cells.

Of the four factors, Myc is induced by skeletal muscle exercise. Myc may serve as a stimulus for naturally induced reprogramming in muscle, making it a useful point of comparison between cells that have been reprogrammed through overexpression of Yamanaka factors and cells that have been reprogrammed for exercise – “reprogramming” in the last case that reflects how. an environmental stimulus can change the accessibility and expression of genes.

The researchers compared the skeletal muscle of mice that had been allowed to exercise late in life to the skeletal muscle of mice that overexpressed OKSM in their muscles, as well as to genetically modified mice limited to the expression of only Myc in his muscles.

Ultimately, the team determined that exercise promotes a molecular profile consistent with partial epigenetic programming. That is, exercise can mimic aspects of the molecular profile of muscles that have been exposed to Yamanaka factors (which show the molecular characteristics of younger cells). This beneficial effect of exercise can be partly attributed to the specific actions of Myc in muscle.

While it would be easy to hypothesize that one day we could be able to manipulate Myc in muscle to achieve the effects of exercise, thus sparing us the current hard work, Murach avis that would be the wrong conclusion to draw.

For this paper, the researchers compared aged mice that had access to a weighted exercise wheel with mice that underwent epigenetic reprogramming via the expression of Yamanaka factors. The image is in the public domain

First, Myc would never be able to replicate all the downstream effects that exercise has throughout the body. It is also the cause of tumors and cancers, so there are inherent dangers in manipulating its expression.

Instead, Murach thinks that the manipulation of Myc could be better used as an experimental strategy to understand how to restore exercise adaptation to old muscles that show a decrease in response.

It could also be a means to supercharge the exercise response of astronauts in zero gravity or bedridden people who have only a limited capacity for exercise. Myc has many effects, both good and bad, so defining the benefits may lead to a safe therapy that could be effective for humans down the road.

Murach sees his research as further validation of the exercise as a polypill. “Exercise is the most powerful drug we have,” he says, and should be considered a health-enhancing — and potentially life-extending — treatment along with medication and a healthy diet.

A molecular signature defining exercise adaptation with aging and partial reprogramming in vivo in skeletal muscle

Exercise promotes functional improvement in aged tissues, but the extent to which it simulates partial molecular reprogramming is unknown.

Using transcriptome profiling from 1) a specific skeletal muscle live October 3/4, Klf4, Sox2and Myc (OKSM) reprogramming-factor expression murine model, 2) an alive specific inducible muscles Myc murine induction model, 3) a high-volume hypertrophic exercise training approach translatable to aged mice, and 4) human exercise muscle biopsies, we collectively defined exercise-induced genes that are common to the partial reprogramming.

Late-life exercise training lowered murine DNA methylation age according to several contemporary muscle-specific clocks.

A comparison of the murine soleus transcriptome after late exercise training to the soleus transcriptome after OKSM induction revealed an overlapping signature that included higher. June B and Sole 1. Furthermore, in this signature, the downregulation of mitochondrial-specific and muscle-enriched genes was preserved in human skeletal muscle trained in long-term exercise; among these was muscle specific Abra/Stars.

Myc is the most exercise-induced OKSM factor in muscle and was elevated after exercise training in aged mice. A MYC boost rewired the global soleus muscle methylome, and the transcriptome after a MYC boost partially recapitulated OKSM induction.

A common signature also emerged in MYC-controlled murine transcriptomes and exercise adaptation, including lower specific muscles. Melusina and associated reactive oxygen species Romans 1.

With MycOKSM, and exercise training in mice and habitual exercise in humans, the complex I accessory subunit I am fb11 was lower; low I am fb11 it is related to the longevity of rodents. Collectively, exercise shares similarities with genetics alive partial reprogramming.

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