Effects of N-acetylcysteine on aging cell and obesity complications in obese adults: a randomized, double-blind clinical trial

Abstract

BackgroundWe decided to conduct this study with the aim of investigating the effects of N-Acetylcysteine (NAC) on obesity complications and senescence of visceral adipose tissue in obese adults.Methods and analysisThe present study was conducted as a randomized clinical trial (RCT) (Clinical trial registry number: IRCT20220727055563N1) on 40 obese adults candidates for bariatric surgery, who were randomly assigned to receive 600 mg of NAC (n = 20) or placebo as a control (n = 20) for 4 weeks. During bariatric surgery, visceral adipose tissue was used to examine gene expression and senescence cells using SA-β-gal.ResultsOur findings showed that intervention with NAC significantly reduces SA-β-gal activity (as a marker of senescence) and expression of p16 and interleukin 6 (IL-6) genes in the visceral adipose tissue compared to placebo in obese adults for 4 weeks. In addition, our findings showed the potential and beneficial effect of NAC administration on reducing the levels of inflammatory factors including IL-6 and high-sensitivity C-reactive protein (hs-CRP), as well as the level of fasting blood sugar (FBS), homeostatic model assessment of insulin resistance (HOMA-IR), and insulin compared to placebo after adjusting for confounders. No significant effect was indicated on anthropometric factors and lipid profile.ConclusionFindings showed that NAC, in addition to having a potential beneficial effect on reducing some of the complications caused by obesity, seems to have synolytic/senomorphic potential as well.Clinical trial registration[https://clinicaltrials.gov/], identifier [IRCT20220727055563N1].

The interplay between obesity, immunosenescence, and insulin resistance

“…Senescent T-cells gradually accumulate in organisms as they age and cause chronic inflammation in adjacent tissues through the secretion of SASP. This process leads to a deterioration in organ function and contributes to the development of several age-related chronic conditions, including cardiovascular disease, endocrine and metabolic disorders, cancer, Alzheimer's disease, and autoimmune diseases [ 9 – 12 ]. During the process of chronological aging, various types of cells undergo cellular senescence, leading to the development of a senescent phenotype.…”

“…Most types of cells in both the innate and adaptive immune systems undergo age-related alterations, particularly T-cells, which have a greater potential capacity for proliferatio [ 18 ]. Furthermore, chronic low-grade inflammation caused by senescence in adipose tissue and immune cells contributes to the development of obesity-related diseases [ 12 , 19 ], involves a complex interplay of immune system responses, including acquired immunity mediated by T and B cells, as well as innate immunity involving macrophages [ 20 , 21 ]. Previous studies have shown that obesity accelerated immunosenescence, independent of chronological aging [ 22 , 23 ].…”