overview: Exercise has an epigenetic effect that promotes youthfulness in aging organisms, new research reports.
sauce: University of Arkansas
Recent papers published in Journal of Physiology It deepens the claim of the youthful-promoting effects of exercise on aging organisms and builds on previous research conducted in laboratory mice nearing the end of their natural lifespan with access to a weighted exercise wheel.
The highly detailed paper “Molecular Signatures Defining Exercise Adaptation by Aging and In Vivo Partial Reprogramming in Skeletal Muscle” lists a whopping 16 co-authors, 6 of whom belong to the U of A. doing.
The corresponding author is Kevin Murach, assistant professor in the Department of Health, Human Performance and Recreation, A University, and the first author is a student at Ronald G. Murach’s Molecular Muscle Mass Regulation Laboratory.
For this paper, the researchers compared aged mice with access to a weighted exercise wheel to mice that underwent epigenetic reprogramming via expression of the Yamanaka factor.
Yamanaka factors are four protein transcription factors (Oct3/4, Sox2, Klf4, and c-Myc, often abbreviated as OKSM) that can convert highly specified cells (such as skin cells) back into stem cells. ) am. A younger, more adaptable state.
For this discovery, Dr. Shinya Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012. At appropriate doses, systemic induction of Yamanaka factor in rodents can ameliorate the characteristics of aging by mimicking the adaptations common to more youthful animals. cell.
Of the four factors, Myc is induced by skeletal muscle exercise. Myc may serve as a naturally-induced reprogramming stimulus in muscle, which is useful for comparing cells reprogrammed by Yamanaka factor overexpression with those reprogrammed by exercise. . Environmental stimuli can alter gene accessibility and expression.
The researchers compared the skeletal muscles of mice allowed to exercise later in life to those of mice that overexpressed OKSM in the muscles, and genetically modified mice that were restricted to overexpressing Myc only in the muscles. bottom.
Ultimately, the team determined that exercise promotes a molecular profile consistent with epigenetic partial programming. That is, exercise can mimic aspects of the molecular profile of muscles exposed to Yamanaka factors (thus exhibiting more youthful cell molecular properties). This beneficial effect of exercise may be due in part to the specific actions of Myc in muscle.
It’s easy to hypothesize that one day we might be able to manipulate Myc in muscles to achieve the benefits of exercise and save real hard work, but Murach said that’s a false conclusion. I warn you when it becomes
First, Myc cannot replicate all the downstream effects of exercise on the whole body. It is also responsible for tumors and cancer, so there are inherent risks in manipulating its expression.
Instead, Murach believes that manipulating Myc is the best way forward as an experimental strategy to understand how to restore exercise adaptations to older muscles that exhibit reduced responsiveness.
Perhaps it could also be a means of supercharging the exercise response of weightless astronauts or bedridden people with limited exercise capacity. Myc has many effects, both good and bad, so defining what is beneficial could lead to effective and safe treatments in humans in the future.
Murach sees their study as further validation of exercise as a polypill. “Exercise is the most powerful medicine we have,” he says, and along with medicine and a healthy diet, it should be seen as a treatment that enhances health and potentially extends life.
About the Movement, Genetics, and News in Aging Research
author: press office
sauce: University of Arkansas
contact: Press Office – University of Arkansas
image: image is public domain
Original research: closed access.
“Molecular features defining age-related exercise adaptation and in vivo partial reprogramming of skeletal muscleBy Ronald G. Jones et al. Journal of Physiology
See also
overview
Molecular features defining age-related exercise adaptation and in vivo partial reprogramming of skeletal muscle
Exercise promotes functional improvement in aged tissues, but the extent to which it simulates partial molecular reprogramming is unknown.
1) Use of skeletal muscle-specific transcriptome profiling in vivo Oct3/4, Klf4, socks 2When my C (OKSM) mouse model expressing reprogramming factors, 2) in vivo Inducible muscle specific my C Exercise-induced genes common to partial reprogramming were collectively defined by an induced mouse model, 3) a translatable mass hypertrophic exercise training approach in aged mice, and 4) a human locomotor muscle biopsy.
Late-life exercise training reduced DNA methylation age in mice according to several modern muscle-specific clocks.
A comparison of the soleus muscle transcriptome of mice after exercise training in old age and that of the soleus muscle transcriptome after OKSM induction revealed that a higher jumbi When sun 1Also within this signature, downregulation of specific mitochondrial and muscle-enriched genes was conserved in long-term exercise-trained human skeletal muscle.Among these were muscle-specific oil/star.
my C was the OKSM factor most induced by muscle exercise and was elevated after exercise training in aged mice. A pulse of MYC rewired the global soleus methylome, and the transcriptome after the MYC pulse partially recapitulated OKSM induction.
Common features also appeared in the MYC-regulated and exercise-adapted transcriptomes of mice. Mersin and reactive oxygen species-related Lomo 1.
When my COKSM, and exercise training in mice and habitual exercise in humans, the complex I auxiliary subunit Ndufb11 was lower; lower Ndufb11 related to the lifespan of rodents.Collectively, exercise shares similarities with genetics in vivo Partial reprogramming.
