What a difference a day makes in a muscle
Researchers at King’s College London are investigating how the circadian clock in muscles affects muscle growth
Muscles can grow in just 24 hours. It takes weeks, months, sometimes even years to notice any difference in your muscles and in all that time, your muscle isn’t just static; it has its own daily routine. Like clockwork, it experiences growth and breakdown every single day.
Pop Quiz: Does muscle get built up or broken down as you sleep?
It may surprise you to find out that not only do muscles keep track of time, but they build and degrade at different times of day. Contrary to the common-sense belief that night is a time of universal regeneration, it seems that muscles carry out a number of catabolic (break-down) processes at night and anabolic (build-up) processes in the day. The more proactive body-building types out there may ask: does that mean an evening gym-session won’t build as much muscle as a morning one? And, perhaps more problematically: can I take something to boost that day-time synthesis or stop that night-time degradation? It’s looking like a yes-inclined-maybe for both of those but there’s much work to be done here. Work that Jeff Kelu at King’s College London has been doing for years now.
Dr Kelu can observe muscle growth directly. Looking through the transparent membrane of zebrafish larvae, you could see the growth too. These zebrafish aren’t just ordinary zebrafish though, they are genetically modified with disrupted muscle clocks. These fish show some interesting features in their muscle growth, namely: they grow as much overnight as they do during the day. Autophagy, the process of cellular breakdown, appears to be inhibited. So, what’s inhibiting it? You’ll have to read Dr Kelu’s paper for the full proposed mechanism but one sneak-peak conclusion is that a circadian-involved gene called NR1D1 is a likely culprit.
Dr Kelu’s genetically modified zebrafish
As with any gene of consequence, the next big question is how can we target this using medication? Now, hold your horses. Whilst NR1D1 is a fascinating target to set our sights on, it’s also a precarious and complex one – on the one hand, its apparent effect on autophagy in muscle cells could be leveraged to reduce age-related muscle loss (and who doesn’t want to see their grandmother lift more than them?) but on the other hand, its role in wider circadian regulation may mean that interference could disrupt other circadian regulated processes - crucial processes such as sleep and immune cell activation. It’s all a bit of a minefield, so understanding the fundamentals is crucial for getting things right. Dr Kelu’s work in elucidating those fundamentals is laying the foundation for medical interventions and evidence-based workouts but, unlike muscle growth, it may just take a little longer than 24 hours.
Dr Jeff Kelu’s previous paper investigated how muscle growth follows a circadian pattern even in the absence of movement
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Lorena Rosen, edited by Jeff Kelu
9 November 2024