Serum Myostatin and IGF-1 as Gender-Specific Biomarkers of Frailty and Low Muscle Mass in Community-Dwelling Older Adults.

OBJECTIVES

(i) To investigate serum myostatin (absolute and normalized for total body lean mass (TBLM)) and IGF-1 as biomarkers of frailty and low relative appendicular skeletal muscle mass (RASM) in older adults, and; (ii) to examine gender differences in the association of serum myostatin and IGF-1 levels with frailty and low RASM.

DESIGN

Cross-sectional study.

SETTING

The "Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and predicting frailty and functional decline in community-dwelling Asian older adults Study" (GERI-LABS) study in Singapore.

PARTICIPANTS

200 subjects aged 50 years and older residing in the community.

MEASUREMENTS

Frailty was assessed using the modified Fried criteria. Low RASM was defined using cutoffs for height-adjusted appendicular skeletal muscle mass measured by dual-energy X-ray absorptiometry as recommended by the Asian Working Group for Sarcopenia. Comorbidities, cognitive and functional performance, physical activity and nutritional status were assessed. Blood samples collected included serum myostatin, insulin-like growth factor 1 (IGF-1) and markers of inflammation (total white cell count, CRP, IL-6 and TNFaR1). Subjects were classified into 4 groups: Frail/Prefrail with low RASM (Frail/Low RASM), Frail/Prefrail with normal RASM (Frail/Normal RASM), Robust with low RASM (Robust/Low RASM) and Robust with normal RASM (Robust/Normal RASM).

RESULTS

63 (32%) subjects were classified as Frail/Low RASM, 53 (27%) Frail/Normal RASM, 28 (14%) Robust/Low RASM and 56 (28%) Robust/Normal RASM respectively. Frail/Low RASM subjects were older and had lower BMI compared to Frail/Normal RASM and robust subjects. Mean (SE) normalized myostatin levels were higher in Frail/Low RASM compared to Frail/Normal RASM subjects (1.0 (0.04) versus 0.84 (0.05) ng/ml/kg, P=0.01). Median (IQR) IGF-1 level was lower amongst Frail/Low RASM subjects compared to Frail/Normal RASM subjects (102.3, (77.7, 102.5) vs 119.7 (82.7, 146.0) ng/ml, P=0.046). No differences in myostatin or IGF-1 were observed among robust individuals with or without low muscle mass. In adjusted multinomial logistic regression models with Robust/Normal RASM as the reference group, myostatin (P=0.05) and IGF-1 (P=0.043) were associated with Frail/Low RASM status in the whole cohort. When stratified by gender, myostatin was significantly associated with Frail/Low RASM status in men only (P=0.03). In women, serum IGF-1 was associated with Frail/Low RASM status (P=0.046), but not myostatin (P=0.53).

CONCLUSION

Serum myostatin, normalized for TBLM in men and IGF-1 in women are potential biomarkers for frail individuals with low RASM, and may identify a target group for intervention.