Mechanisms for a Novel Muscle Memory

Mange har historier å fortelle om at fordi de var sterke som unge, har de lett kunne trene seg opp igjen selv om de ikke har trent kontinuerlig og har mistet muskelmassen. Hittil har slike fenomener vært tilskrevet motorisk læring av tekniske ferdigheter, og man har ikke tenkt seg at det er noen hukommelse eller læringsmekanisme i musklene selv. Vi har imidlertid i dyreforsøk vist at det er en cellulær hukommelse i muskelcellene selv. I dette prosjektet viser vi at muskelcellene er DNA-fattige og at dette begrenser cellestørrelsen og dermed kraften. Vi viser at hukommelsen kan være basert dels på en permanent økning i antallet cellekjerner og dels på epigenetiske mekanismer som regulerer genenes tilgjengelighet.

Det viktigste er at prosjektet har etablert muskelhukommelse som et viktig forskningsfelt i idrettsfysiologien. Forskningen har hatt betydelig innflytelse både vitenskapelig, men high impact publikasjoner, men er også svært hyppig omtalt og diskutert i idrettsmiljøer med en stor mengde omtaler i mane land og på mange språk i ulike idrettsfora. Prosjektet påirker måten man tenker om trening i ulike deler av livtsløpet.

The muscle fibres are the largest cells in the body, and the size generally determines the force. While almost all other cells contain only one nucleus, muscle fibres have several hundred, and it is believed that each of them support a certain volume of cytoplasm. The textbook understanding is that during strength exercise fibres hypertrophy and new nuclei are added to pre existing fibres from fusing stem cells, while during disuse, fibres shrink and loose nuclei by apoptosis. We have developed in vivo imaging techniques where single nuclei can be followed in the animal with time-lapse microscopy. These techniques have suggested that the textbook model is wrong and that nuclei are not lost from muscle fibres during atrophy. Since we confirm that nuclei are added during hypertrophy, we suggest that the permanent increase in the number of nuclei after an hypertrophy episode could represent a form of cellular "memory". Our main goal is to provide convincing data for the existence of a "muscle memory", such that an elevated number of nuclei is beneficial in aiding later strength training. The ability to generate new muscle nuclei is impaired in the elderly; thus, the demonstration of a muscle memory should lead to a health advice for early exercise in order to counteract weakness in the elderly. We have observed that anabolic steroids generate new muscle nuclei in animals, similar experiments will be performed in humans, and might lead to changes in the worlds anti doping rules. In patients we will investigate muscle wasting with improved histological methods in order to find out if our new model also applies to humans, thus demonstrating that muscle wasting is not a degenerative disease. In animal models we will investigate the cellular dynamics of myonuclei and the molecular mechanisms underlying centronuclear myopathies. In addition to nucleic number as a novel memory mechanism we will investigate if genome imprinting also plays a role for the "memory.