SCIENCE

How Body Clocks Might Be Behind Muscle Loss in Low Testosterone

Wed Jul 09 2025

Testosterone levels dropping in men can lead to muscle loss, especially in the limbs. But why does this happen? Scientists have been digging into this question.

The Role of Per1 and Per2 Proteins

They found that when testosterone levels drop, the body's internal clocks in muscles get messed up. This mess-up is linked to higher levels of two proteins called Period 1 (Per1) and Period 2 (Per2).

These proteins act like brakes on the body's clock. When they pile up, they might be telling muscles to shrink.

Experiments and Findings

Scientists conducted experiments to understand this better:

  • Muscle Shrinkage with Extra Per2: They made muscles in a dish grow bigger, then added extra Per2. The muscles shrank.
  • Muscle Retention without Per2: When they took away Per2 in mice, the muscles stayed bigger even after testosterone was removed.

Per1 does the same thing. When scientists added extra Per1 to muscles in a dish, the muscles shrank too.

The Chain Reaction Involving Inflammation

It seems like these proteins might be causing muscles to shrink by starting a chain reaction. This chain reaction might involve inflammation.

  • Per1 and Per2 Pile-Up: When Per1 and Per2 pile up, they seem to turn on genes that cause inflammation.
  • Inflammation and Muscle Shrinkage: This inflammation might be telling muscles to shrink.

Real-Life Implications

Scientists also found that when testosterone levels drop in real life, these same inflammatory genes get turned on in muscles. So, it seems like Per1 and Per2 might be a big part of why muscles shrink when testosterone levels drop.

New Discovery and Future Hope

This is a new discovery. It might help scientists find new ways to help men keep their muscle when testosterone levels drop.

questions

    How might the autocrine-mediated mechanism involving inflammation be targeted to prevent muscle atrophy without affecting the molecular clock?
    Can the inflammatory gene expression signature induced by Per1 and Per2 overexpression be mitigated by anti-inflammatory treatments?
    How does the overexpression of Per2 specifically affect the tibialis anterior muscle compared to other muscles?

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