Growth differentiation factor-15 as a biomarker for sarcopenia in aging humans and mice

Sarcopenia is a pathologic status characterized by impaired muscle strength or function accompanying decreased muscle mass. It results in increased vulnerability to chronic diseases. Despite growing clinical concerns about sarcopenia in an aging society, there are few validated biomarkers for age-related sarcopenia. We tested the potential of growth differentiation factor-15 (GDF-15) as a biomarker for sarcopenia in mice and humans across wide age ranges. We used four groups of mice (6, 10, 14, and 18 months old) to explore the association between GDF-15 levels and age, muscle mass, and endurance capacity. Among those four groups, 6- and 18-month-old mice were exposed to 8 weeks of treadmill exercise. The GDF-15 levels were measured in serum and muscle at baseline and after exercise intervention. The body composition was assessed using animal dual-energy X-ray absorptiometry (DXA). GDF-15 levels in tissue and serum increased with age in these mice. The serum levels of GDF-15 had a strong negative correlation with both muscle weight and exercise endurance capacity. Expression of GDF-15 in muscle also had a negative trend with muscle weight and endurance capacity. The muscle expression of GDF-15 was significantly attenuated after 8 weeks of exercise compared with the group without exercise, particularly in older mice. GDF-15 levels were also related to functional capacity and showed responses to therapeutic exercise intervention in this model. We also measured serum GDF-15 levels and muscle mass using DXA in healthy human adults (19 men and 18 women). As in mice, serum levels of GDF-15 were correlated positively with age, but negatively with muscle mass in these subjects. These findings support the potential of GDF-15 as a biomarker for age-related sarcopenia.