New ways to keep our muscles strong even in old age
Autophagy, or cell cleansing, is a crucial mechanism in cell maintenance that creates a balance between degradation and renewal. While excess autophagy can increase tissue degeneration, a lack of autophagy also contributes to degenerative processes. The interaction between the AMPK metabolic pathway, which promotes autophagy, and the mTOR metabolic pathway, which inhibits it, underscores the complexity of the regulation of this process.
Within the spectrum of autophagy, mitophagy, which is primarily controlled by PGC-1α and targets dysfunctional mitochondria for degradation, is a key focus. Despite its complexity, the exact biochemical processes of autophagy are not yet fully understood, and research is ongoing.
A study involving 575 participants, predominantly of European origin and with an average age of 75.9 years, investigated the relationship between the expression of genes associated with autophagy and functional parameters. RNA sequencing of 260 selected genes associated with autophagy, mitophagy and the mTOR signaling pathway revealed interesting correlations with mitochondrial function and physical performance, particularly 400-meter running speed.
Interestingly, genes directly involved in autophagy did not appear to have a major impact on the functioning of our muscles in old age. However, other genes, such as Foxo1, which help regulate autophagy, showed unexpected correlations. Instead of helping, they appeared to be associated with poorer muscle function.
In contrast, genes involved in how our bodies use energy and manage our mitochondria were associated with better muscle function. Influencing the mTOR pathway, which controls cell growth, also showed promise for improving muscle performance in older adults.
These findings challenge everything we thought we knew about Foxo1. It appears that when autophagy is not functioning properly, our bodies try to compensate by ramping up Foxo1.
By interfering with the mTOR signaling pathway, new ways could be found to keep muscles strong even in old age. This opens up exciting possibilities for new therapies that help older people stay strong and healthy.
References
Coen, P. M., Huo, Z., Tranah, G. J., Barnes, H. N., Zhang, X., Wolff, C. A., Wu, K., Cawthon, P. M., Hepple, R. T., Toledo, F. G. S., Evans, D. S., Santiago-Fernández, O., Cuervo, A. M., Kritchevsky, S. B., Newman, A. B., Cummings, S. R., & Esser, K. A. (2024). Autophagy gene expression in skeletal muscle of older individuals is associated with physical performance, muscle volume and mitochondrial function in the study of muscle, mobility and aging (SOMMA). Aging Cell, 00, e14118. https://doi.org/10.1111/acel.14118