Circulating GDF11 levels are decreased with age but are unchanged with obesity and type 2 diabetes

Abstract

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β (TGFβ) superfamily which declines with age and exerts anti-aging regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting casting doubts about its true functional actions. The aim of the present study was to compare the circulating concentrations of GDF11 in individuals of different ages as well as body weight and glycemic status. Serum concentrations of GDF11 were measured by ELISA in 319 subjects. There was a significant increase in GDF11 concentrations in people in the 41-50 y group and a decline in the elder groups (61-70 and 71-80 y groups, P=0.008 for the comparison between all age groups). However, no significant correlation between fat-free mass index (FFMI), a formula used to estimate the amount of muscle mass in relation to height, and logGDF11 was observed (r=0.08, P=0.197). Moreover, no significant differences in circulating concentrations of GDF11 regarding obesity or glycemic status were found. Serum GDF11 concentrations in humans decrease in older ages being unaltered in obesity and T2D. Further studies should determine the exact pathophysiological role of GDF11 in aging.

Keywords: GDF11; aging; fat-free mass; obesity; type 2 diabetes.

Figure 1

Effect of aging on serum GDF11 concentrations. (A) Comparison of serum GDF11 in the whole sample aged between 18 and 79 y segregated by decades (≤30 y, n=53), (31-40 y, n=54), (41-50 y, n=51), (51-60 y, n=54), (61-70 y, n=59), (71-80 y, n=48). Box represents interquartile range and median inside, with whiskers plotted according to the Tukey method. Statistical differences between groups were analyzed by one-way ANOVA followed by Fisher’s LSD tests. *P<0.05, **P<0.01 and ***P<0.001. (B) Scatter diagram showing the relationship between circulating concentrations of GDF11 and age. Pearson’s correlation coefficient and P value are indicated. The quadratic line of adjustment of data is shown. (C) Scatter diagrams showing the correlation between circulating concentrations of GDF11 and age in the subjects segregated by being below (left) or over (right) 50 years of age. Pearson’s correlation coefficients and P values are indicated.

Figure 2

Correlation of GDF11 levels with FFMI. (A) Comparison of fat-free mass index (FFMI) in the whole sample aged between 18 and 79 y segregated by gender (males in grey and females in white) and decades (≤30 y, males n=18, females n=31), (31-40 y, males n=20, females n=34), (41-50 y, males n=24, females n=27), (51-60 y, males n=21, females n=33), (61-70 y, males n=14, females n=35), (71-80 y, males n=20, females n=22). Box represents interquartile range and median inside, with whiskers plotted according to the Tukey method. Statistical differences between groups were analyzed by two-way ANOVA. (B) Scatter diagram showing the relationship between circulating concentrations of GDF11 and FFMI. Pearson’s correlation coefficient and P value are indicated.

Figure 3

Effect of gender, obesity and type 2 diabetes on GDF11 levels. (A) Comparison of serum GDF11 concentrations between males (n=126) and females (n=193). Statistical difference was analyzed by two-tailed unpaired Student’s t test. (B) Comparison of serum GDF11 concentrations between lean (n=49) and obese (n=228) individuals. Statistical difference was analyzed by two-tailed unpaired Student’s t test. (C) Serum GDF11 concentrations in the lean normoglycemic (LN-NG, n=40), obese normoglycemic (OB-NG, n=93), obese with impaired glucose tolerance (OB-IGT, n=46), and obese with type 2 diabetes (OB-T2D, n=47) groups of the whole sample. Statistical differences between groups were analyzed by one-way ANOVA. For the three figures, box represents interquartile range and median inside, with whiskers plotted according to the Tukey method.