Age-Related Remodeling of Cross-Tissue Transcriptional Coordination in the Human Motor System

Aging across the various tissues that make up the human motor system is not well understood. Researchers have now combined data from the Genotype-Tissue Expression (GTEx) project and Gene Expression Omnibus (GEO) to gain insight. This data includes 7,145 samples from 15 different human tissues involved in three key aspects of motor control - signal transmission, central coordination, and peripheral execution.

By using advanced modeling techniques, the researchers were able to map out how transcriptional activity changes with age in these tissues.

Many genes associated with aging were found in multiple tissues, but the way they were regulated, the strength of their effects, and the timing of their changes varied greatly between tissues. Interestingly, the aging process did not follow a consistent pattern from the central parts of the motor system out to the peripheral areas.

Instead, the degree of cross-tissue transcriptional coordination increased as people aged from their early to mid-adult years. It reached a peak around middle age before gradually declining in later life. This pattern was seen at both the individual gene level and the level of larger biological pathways.

The researchers found that this late-life loss of coordination in the motor system was particularly noticeable in the nerves that connect to muscles and in multiple connections involving the striatum, a brain region important for movement control. Their analysis suggests that aging affects the motor system in a complex way, with tissues responding differently but all built on a shared molecular basis of aging.

There is also a gradual reorganization of how these different tissues coordinate with each other, which becomes more pronounced in older age and is especially apparent in the peripheral nerve-skeletal muscle system.