Comment on a Recent Article Titled “Irisin Correlates Positively With BMD in a Cohort of Older Adult Patients and Downregulates the Senescent Marker p21 in Osteoblasts”

Abstract

In a recent issue of JBMR, Colaianni and colleagues reported the relationship of circulating irisin levels, a myokine synthesized from skeletal muscle, with bone and muscle parameters in a sample of older adults.(1) They showed that FNDC5 expression, an irisin precursor, in muscle biopsies positively correlated with osteocalcin mRNA in bone biopsies, suggesting a connection between these tissues. Interestingly, the treatment with irisin decreased p21 mRNA expression, a senescence marker, in osteoblasts in vitro. These findings may be a guide for novel therapeutic approaches to delaying age-related muscle atrophy and bone loss. However, a few points are worth discussing. The authors may not have accounted for several factors that could influence their results, including chronic diseases and some selected drugs. The prevalence of chronic conditions increases after the age of 60 years, and many older people develop more than one chronic disease. A recent cross-sectional study of 740 participants showed an association of serum irisin with adiposity, glucose tolerance, and insulin resistance in middle-aged individuals.(2) In the same study, patients with diabetes mellitus (DM) had lower irisin levels than those without DM.(2) Correspondingly, serum irisin concentrations significantly decreased among patients with DM in a cohort of adults older than 60 years.(3) On the other hand, experimental studies showed that bolus intravenous administration of irisin decreased arterial blood pressure by reducing vascular endothelial dysfunction via upregulation of NO synthesis and activating the AMPK-Akt-eNOS pathway.(4, 5) Lower circulating irisin levels were found to be associated with high systolic and diastolic blood pressure in patients with preeclampsia.(6) Besides, cardiac muscles are an important source of irisin synthesis, and the change in heart function may alter the production of this protein.(7) Many older individuals are prescribed drugs to manage chronic diseases. Metformin therapy is the first-line agent in the treatment of DM in older individuals. In an interventional study of patients with polycystic ovary syndrome, 3 months of metformin treatment decreased serum irisin levels and improved insulin resistance.(8) Lowering blood pressure with amlodipine and valsartan increased the circulating levels of irisin in patients with untreated essential hypertension.(9) An animal study showed that statin treatment increased irisin levels in skeletal muscle.(10) I would like to ask the authors whether they provide some data on this population's comorbidities and medication for diabetes mellitus, hypertension, and hyperlipidemia. Inclusion of new data in statistical analysis could help make the results stronger. New findings could raise the importance of this research, which aimed to explore the role of irisin in bone and muscle senescence.