Professor Adam P. Sharples
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profadamsharples.bsky.social
Professor Adam P. Sharples
@profadamsharples.bsky.social
Professor of Molecular Physiology | Our Group 1st Demonstrated that Human Skeletal Muscle Possesses an Epigenetic Memory of Exercise -Our DNA Remembers Exercise! | ExProRugby
Special thanks to collaborators Jonathan Jarvis, Sue Bodine, @hughesdc-muscle.bsky.social, Daniel Owens, Truls Raastad, Jonas Treebek, Emilie Dalbram, Max Ullrich,
Stian Christiansen, Hazel Sutherland, James Boot, Eva Wozniak and Charles Mein. As well as Olivier Seynnes, Jostein Hallen, Siri & Hege!
October 31, 2025 at 4:34 PM
So thankful to have been able to work closely with the incredible Daniel C. Turner who spearheaded all the experiments!
October 31, 2025 at 4:34 PM
This work was supported by the Research Council of Norway (RCN - 314157).

So grateful to all the participants who agreed to lose their muscle (twice!) and made this possible!
October 31, 2025 at 4:34 PM
Key takeaway:
Muscle “remembers” disuse at the molecular level.
Young muscle = transcriptional protection.
Aged muscle = exaggerated transcriptional vulnerability.
Epigenetic marks may in-part encode this memory.
October 31, 2025 at 4:34 PM
Nicotinamide riboside (NR) supplementation in human MuSCs post-atrophy improved myotube size

Suggests NAD⁺ salvage may support recovery from atrophy (with more in-vivo work required to confirm!)
October 31, 2025 at 4:34 PM
NAD⁺ biosynthesis gene NMRK2 was among the most downregulated genes after both atrophy periods.

Reduced NAD⁺ levels and mtDNA loss was observed to be greatest after repeated atrophy in aged muscle.
October 31, 2025 at 4:34 PM
NR4A1 stayed suppressed during recovery with hypermethylation in young muscle.

AChR genes (CHRNA1, CHRND) were epigenetically primed & upregulated after repeated disuse - suggesting a memory of atrophy in these genes.
October 31, 2025 at 4:34 PM
DNA methylome analyses revealed conserved hypermethylation of mitochondrial and aerobic metabolism genes across species after disuse atrophy.

Some epigenetic marks were retained or exaggerated with repeated disuse.
October 31, 2025 at 4:34 PM
In aged rats, repeated disuse led to greater muscle loss.

Despite transcriptional recovery after initial atrophy, aged muscle showed an exaggerated transcriptional suppression after repeated disuse suggesting a detrimental molecular memory.
October 31, 2025 at 4:34 PM
In young adults, repeated immobilization caused similar muscle loss as initial disuse.

However, the transcriptional response was blunted-especially in aerobic metabolism & mitochondrial genes.

Suggests a protective molecular memory characterised by transcriptional attenuation.
October 31, 2025 at 4:34 PM