Different Pattern in Circulating MicroRNA-22-3p Levels Between Patients With Primary Versus Secondary Sarcopenia

Sarcopenia, characterized by decreased skeletal muscle mass and strength, is classified as "primary" (due to aging) or "secondary" (due to diseases). MicroRNA-22-3p (miR-22) regulates muscle differentiation and function. We assessed the diagnostic value of circulating miR-22 levels in patients with primary and secondary sarcopenia. miR-22 levels were evaluated in 61 older adults from the "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) study and in 176 heart failure (HF) patients from the "Studies Investigating Co-morbidities Aggravating HF" (SICA-HF). miR-22 expression profile was measured in serum by miR-specific TaqMan quantitative real-time PCR. In SPRINTT, 33 participants (54.1%) had primary sarcopenia. Subjects with primary sarcopenia had slower gait speed (0.7 [0.6-0.8] vs. 0.8 [0.7-1.0] m/s; p < 0.001) than those without sarcopenia. Multivariate analysis showed miR-22 as an independent predictor of sarcopenia (adjusted OR 3.087, 95% CI 1.441-6.611, p = 0.004). In SICA-HF, 28 patients (15.9%) had secondary sarcopenia. Sarcopenic HF patients were older (74.5 [68.7-80.2] vs. 68.4 [60.9-74.8] years; p = 0.001), had lower left ventricular ejection fraction (31.1 [26.2-47.5] vs. 40.0 [30.0-55.0] %; p = 0.025), lower handgrip strength (31.1 ± 6.0 vs. 37.0 ± 13.0 kg; p = 0.016) and lower absolute peak oxygen uptake (1181.3 ± 379.5 vs. 1593.0 ± 487.0 mL/min; p < 0.001) compared with those without sarcopenia. Multivariate logistic regression analysis showed miR-22 as significantly associated with sarcopenia in HF patients (adjusted OR 0.409, 95% CI 0.193-0.867, p = 0.020). miR-22 levels are significantly associated with both primary and secondary sarcopenia, suggesting its potential as a novel epigenetic biomarker of skeletal muscle dysfunction.