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.

Abstract

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 3 protein (FSTL3) are inhibitory proteins of both GDF-8 and GDF-11. Using highly specific LC-MS/MS assays for GDF-11 and GDF-8 and immunoassays for follistatin and FSTL3, we quantified the association of these factors with muscle size, strength and physical performance in two prospective cohort studies of community-dwelling older adults (Health ABC and CHS). 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. FSTL3 (and perhaps follistatin) were negatively associated with lean mass and had variable associations with other variables. In contrast, GDF-11 was not significantly associated with strength or performance. GDF-8 and its binding proteins, follistatin and FSTL3, may constitute a counter-regulatory system (chalones) to restrain age-related loss of muscle mass and strength.