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

Abstract

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.

Keywords: IGF-1; Sarcopenia; frailty; myostatin.