Research conducted by scientists at Duke-NUS Medical School, in collaboration with Singapore General Hospital and Cardiff University, has uncovered a crucial cellular mechanism that explains how exercise can help maintain muscle function as individuals age. The study reveals that regular physical activity not only enhances muscle growth but also restores the cellular machinery responsible for repairing damaged tissue efficiently.
Muscle function typically starts to decline from midlife, leading to challenges such as increased risk of falls, slower recovery from injuries, and poorer regulation of blood sugar levels. The research identifies the growth pathway known as mTORC1 as pivotal in maintaining muscle health. This pathway regulates protein production and tissue maintenance. As people age, however, the balance within this system is disrupted, resulting in the accumulation of damaged proteins that contribute to muscle weakness.
The team pinpointed a transcription factor named DEAF1 that drives this imbalance in aging muscles. This gene becomes overactive, disrupting the normal protein exchange seen in younger tissues. The activity of DEAF1 is regulated by proteins known as FOXOs, which lose their effectiveness as individuals age, allowing the system to accelerate muscle degradation rather than repair.
Exercise emerges as a critical factor in counteracting these effects. According to Tang Hong-Wen, an associate professor at Duke-NUS, physical activity activates specific proteins that lower DEAF1 levels, thereby restoring balance to the growth pathway. This process enables aging muscles to clear out damaged proteins and rebuild effectively, enhancing strength and resilience.
Lead author Priscillia Choy Sze Mun emphasized the significance of exercise in prompting muscles to “clean up and reset.” By reducing DEAF1 levels, older muscles can regain strength and stability, akin to hitting a rewind button on muscle function. Given the millions of older adults at risk of muscle decline, understanding the role of DEAF1 could lead to innovative strategies for muscle preservation and improved quality of life.
The researchers conducted experiments using older mice and fruit flies, observing a consistent pattern where elevated DEAF1 levels correlated with increased muscle weakness. Conversely, reducing DEAF1 activity restored balance and promoted muscle repair. While these models are simpler than human biology, the underlying processes are likely to mirror those in human tissues, indicating a common age-related dysregulation.
DEAF1’s influence extends beyond muscle tissue; it also affects stem cells, which play a vital role in tissue repair and regeneration. As these stem cells decline with age, manipulating DEAF1 levels could help sustain the benefits of exercise into later life, even for individuals who may not engage in extensive physical activity.
The findings from this study provide crucial insights into the molecular mechanisms behind muscle aging and the restorative effects of exercise. Patrick Tan, a professor at Duke-NUS, remarked on the potential implications of identifying DEAF1 as a key regulator in this process. This research may pave the way for new approaches to harness the benefits of exercise, particularly in societies facing rapidly aging populations.
The study has been published in the journal PNAS (Proceedings of the National Academy of Sciences), offering a foundation for future exploration into muscle health and age-related conditions.
