Background: Aging-induced cardiac hypertrophy and reduced skeletal muscle strength contribute to increased disease risk and life burden in the elderly. FNDC5 acts as a protective muscle factor in both cardiac and skeletal muscle. This study aims to examine the relationship between cardiac FNDC5 and aging-related cardiac hypertrophy and decreased skeletal muscle strength. Methods: Male young C57BL/6 mice (5 months old, n = 6) and aged mice (21 months old, n = 6) were utilized in the study and housed in a specific pathogen-free (SPF) environment. Prior to the experiment, grip strength tests were performed on the mice, and heart tissues were collected for morphological analysis, including the assessment of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and fibronectin type III-containing structural domain 5 (FNDC5) protein levels. Furthermore, myosin heavy chain II (MyHC II), skeletal muscle-specific transcription factor (MyoD), muscle RING-finger protein-1 (MuRF1), and FNDC5 levels were evaluated in the quadriceps muscle. The correlations between heart weight and FNDC5 expression levels, as well as skeletal muscle indices in the mice, were subsequently analyzed. Result: Aging leads to cardiac hypertrophy and reduced expression of PGC-1α and FNDC5 proteins. Concurrently, there is a decline in the strength of skeletal muscle, along with decreased expression of MyHC II and increased expression of MURF1 and MyoD. Correlation analysis demonstrated strong positive associations between myocardial FNDC5 protein levels and limb grip strength, as well as MyHC II, and strong negative associations with MyoD and MuRF1. Conclusion: There may be a significant association between aging-induced cardiac hypertrophy and decreased skeletal muscle strength, with FNDC5 potentially playing a crucial role as a regulatory molecule facilitating communication between the heart and skeletal muscle.
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