Identifying RNA changes in skeletal muscle related to healthy aging

2021

Challenge

An almost constant characteristic of aging in most species, including humans, is the progressive loss of muscle mass, even in people who are actively exercising. This condition, called ‘sarcopenia,’ leads to a disproportionate decline in muscle strength; in some cases, it becomes so severe that it may impair the ability to walk. The biological mechanisms underlying this process are unknown. Previous studies of sarcopenia used less informative technologies and focused on specific populations, such as comparing active and sedentary people, leaving significant gaps in our knowledge of muscle aging in healthy human populations. Challenges in recruiting healthy study participants in all age groups have also caused major obstacles for many studies.

Advance

IRP researchers led by Luigi Ferrucci, M.D., Ph.D., sought to fill in this knowledge gap about age-related changes in the cellular biology of human skeletal muscle by examining levels of different RNA molecules, the genetic material that plays an intermediary role in transforming DNA into functional proteins. Using muscle samples collected from 53 healthy individuals ranging from 22 to 83 years old, the scientists identified 1,134 RNAs that changed significantly with aging. The most notable differences between age groups involved the quantity of RNA related to certain age-related processes, such as muscle repair, the use of the hormone insulin to help cells take in blood sugar, and the arrest of cell division. In addition, RNA sequencing analysis allowed the investigators to identify RNA molecules that encode specific protein variants that changed significantly with age in skeletal muscle, particularly proteins involved in the generation of energy within cells and the development of fat cells to store excess energy.

Impact

Establishing how the quantity and variety of RNA in skeletal muscle changes over the course of healthy aging provides a valuable reference for scientists and clinicians seeking to establish the physiologic and health status of a person’s skeletal muscle. In addition, the insights generated in the study, including into the emergence of new protein variants during aging, will improve our understanding of age-related sarcopenia and accelerate future efforts to uncover targets for preventive and therapeutic interventions.

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