Why Muscles Weaken with Age

Scientists have discovered a hidden protective mechanism in ageing muscles that limits strength to shield cells from damage. In mice, partially restoring a key molecule reversed signs of muscle loss and prevented early death, offering hope for potential treatments for agerelated muscle decline. The muscles naturally become weaker as we get older, but scientists have discovered that some of the changes associated with ageing may actually help protect muscle cells from damage. New research by the University of Copenhagen revealed why ageing muscles shift toward a different type of muscle fibre and identifies a crucial molecule that could offer a new approach to treating muscle loss. Muscle tissue contains bundles of fibres with different functions. Fast-twitch fibres produce powerful, rapid movements but fatigue relatively quickly. Slow-twitch fibres, by contrast, support sustained activity and contain higher concentrations of mitochondria, the cellular structures responsible for producing much of the energy muscles need. As people age, muscle strength declines, and mitochondria become less efficient. Surprisingly, ageing muscles also develop a greater proportion of slowtwitch fibres, even though these fibres depend heavily on the very mitochondria that are losing their ability to function. Researchers have observed similar changes in several conditions that cause muscle wasting. This raises an important question: Why would muscles increasingly rely on an energyproducing system that is becoming less effective? To investigate this puzzle, scientists focused on cardiolipin, a specialised fat molecule located almost exclusively within the inner membrane of mitochondria. Cardiolipin helps maintain the membrane’s distinctive folded architecture, which is essential for proper mitochondrial activity. When cardiolipin is lacking, mitochondria struggle to generate sufficient energy. They also become less capable of producing the chemical signals and essential materials that cells require to function. The researchers discovered that cardiolipin levels decrease in muscle mitochondria from both mice and humans as they age or experience disease. This decline was accompanied by structural abnormalities in the mitochondria and a loss of normal function, as per the ScienceDaily website. To determine whether reduced cardiolipin directly contributes to these changes, rather than simply occurring alongside them, the team experimentally lowered cardiolipin levels in young mice. The results closely resembled what happens during natural ageing. Muscle fibres shifted away from the fast-twitch type toward slow-twitch fibres, matching the pattern previously observed in older mice and humans. Even more strikingly, restoring cardiolipin to approximately twothirds of its normal concentration began reversing muscle wasting and completely prevented the premature deaths seen in the affected animals. Why Ageing Muscles Sacrifice Strength for Protection Further experiments revealed an unexpected explanation for the transformation. Rather than representing only a breakdown in muscle function, the shift toward slow-twitch fibres appears to be a protective response. When cardiolipin concentrations fall, damaged mitochondria produce much larger quantities of reactive oxygen species (ROS). These highly reactive molecules can harm cellular structures, but they also play an important role in signalling that something is wrong. The researchers found that ROS help initiate the transition from fast-twitch to slow-twitch muscle fibres. When they treated muscle cells lacking cardiolipin with an antioxidant to reduce ROS, the transformation became less pronounced. A protein known as ERRγ plays a central role in coordinating this response. It directs cells to reorganise their mitochondria and change their muscle fibre characteristics. When scientists inhibited ERRγ in muscle cells grown in the laboratory, the transition between fibre types stopped entirely, as per the study on ScienceDaily website. The team also discovered how the newly remodelled fibres help defend themselves.