Evaluation of Associations of Growth Differentiation Factor-11, Growth Differentiation Factor-8, and Their Binding Proteins, Follistatin and Follistatin-Like Protein-3, With Measures of Skeletal Muscle Mass, Muscle Strength, and Physical Function in Older Adults.

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JGM, Animals, Humans, Aged, Myostatin, Carrier Proteins, Follistatin, Prospective Studies, Growth Differentiation Factors, Muscle Strength, Proteins, Muscle, Skeletal

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J Gerontol A Biol Sci Med Sci. 2023;78(11):2051-9.








BACKGROUND: Based on studies from animal models, growth differentiation factor-11 (GDF-11) may have rejuvenating effects in humans. GDF-11 has high sequence homology with GDF-8 (also known as myostatin); follistatin and follistatin-like protein-3 (FSTL-3) are inhibitory proteins of both GDF-8 and GDF-11.

METHODS: Using highly specific liquid chromatography with tandem mass spectrometry assays for GDF-11 and GDF-8 and immunoassays for follistatin and FSTL-3, we quantified the association of these factors with muscle size, strength, and physical performance in 2 prospective cohort studies of community-dwelling older adults (Health, Aging, and Body Composition study [Health ABC] and Cardiovascular Health Study [CHS]).

RESULTS: GDF-8 levels were positively associated with thigh muscle cross-sectional area and density in Health ABC (data not available in CHS). GDF-8 levels were positively associated with lean mass (a surrogate of muscle mass) in Health ABC but not CHS, and grip strength in CHS but not Health ABC. FSTL-3 (and perhaps follistatin) was negatively associated with lean mass and had variable associations with other variables. In contrast, GDF-11 was not significantly associated with strength or performance.

CONCLUSIONS: GDF-8 and its binding proteins, follistatin and FSTL-3, may constitute a counterregulatory system (chalones) to restrain age-related loss of muscle mass and strength.