Evaluation of Sirtuin 1 Levels in Peripheral Blood Mononuclear Cells of Patients With Idiopathic Pulmonary Fibrosis

Abstract

Aim: Idiopathic pulmonary fibrosis (IPF) is a devastating lung disorder that is characterized by aggressive and dysbalanced wound healing. IPF is mainly a disease of the elderly and thus is likely to share common pathophysiologic mechanisms with other more age-related diseases. Emerging evidence has linked disturbance of sirtuin-1 (SIRT1) expression and activity with aging and diseases of the elderly. In the present study, we aimed to evaluate SIRT1 expression in the peripheral blood mononuclear cells (PBMCs) of patients with IPF given the lack of studies in the literature.Methods: We enrolled 34 IPF patients and 22 healthy volunteers (age and sex-matched). In both groups, SIRT1 levels were assessed in plasma, cell pellets of PBMCs, and supernatant from PBMCs' culture with and without the addition of 10% human serum. We also measured transforming growth factor β1 (TGF-β1) concentration in plasma from IPF patients and controls.Results: The mean (SD) age (years) of the healthy volunteers was 68.57±6.97 and of the IPF patients was 71.28±5.39 years (p>0.05). The mean SIRT1 concentration was found significantly decreased in the supernatant of PBMCs culture (without the addition of serum) in IPF subjects versus controls (1.97±0.59 ng/ml versus 2.40±0.74 ng/ml, respectively, p=0.047). No significant differences were observed between the two groups in the SIRT1 concentration of all the other materials. TGFβ1 concentration of IPF subjects was significantly increased when compared to controls (1281.38±2742.74 versus 131.11±156.06 ng/ml, respectively, p=0.032). Decreased SIRT1 levels in no-serum supernatant were predictive of IPF, after adjustment for age and sex (p=0.014, OR=0.124 [95%CI: 0.023-0.653]). Conclusion:The findings of decreased concentration of SIRT1 in PBMCs supernatant and increased concentration of TGFβ1 in plasma in IPF patients versus controls provide important insights into the role of SIRT1 in IPF and could serve as a tool for the diagnosis and evaluation of patients with IPF.

Potential role of SIRT-1 and SIRT-3 as biomarkers for the diagnosis and prognosis of idiopathic pulmonary fibrosis

“…A study by Deskata et al in 2022 assessed SIRT-1 levels in plasma and peripheral blood mononuclear cells (PBMC) of IPF patients, and reported significantly lower levels in PBMC from IPF patients compared to controls. Furthermore, the authors concluded that SIRT-1 is predictive of IPF when adjusted for sex and age [ 19 ].…”

Sirtuins and Cellular Senescence in Patients with Idiopathic Pulmonary Fibrosis and Systemic Autoimmune Disorders

“…They showed that SIRT1 levels were statistically significantly lower in the supernatant of PBMCs from patients with IPF compared with those from controls. Furthermore, the likelihood of being in the IPF group was increased by older age and lower SIRT1 levels [ 34 ]. Notably, the activation or overexpression of SIRT1 by resveratrol treatment attenuates the TGF-β1-induced myofibroblast activation by regulating the expression of p300 [ 35 ].…”