Analysis of the regulatory role of Sirtuin 1 on oxidative stress and inflammation in Periodontitis, associated or not with Diabetes.

• Grant number: 24/18782-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2025
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Morgana Rodrigues Guimarães Stabili
• Grantee: Lucas Nogueira Ramos
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Periodontitis is a chronic and multifactorial inflammatory disease associated with a dysbiotic biofilm, characterized by the progressive loss of the tooth insertion apparatus and with a high prevalence, mediated, above all, by the host's innate immune response to an oral microbial challenge. Diabetes mellitus (DM), in turn, is a metabolic disease characterized by chronic hyperglycemia, resulting from deficient insulin production, resistance to the effects of insulin or a combination of both. The disease, which can affect quality of life and public health, is associated with a high risk of complications, including macrovascular disease, neuropathy, nephropathy and delayed wound healing. There is a suggested bidirectional relationship between periodontitis and diabetes, such that periodontal disease (PD) may also contribute to the development of diabetes and vice versa. Sirtuins, a family of nicotinamide adenine-dependent dinucleotides, are a class of enzymes that regulate critical cellular processes such as genome integrity and metabolism, gene silencing, and apoptosis that have been extensively studied in the regulation of aging and age-related diseases. These proteins are also essential modulators of oxidative stress and inflammation, as they can regulate the expression and activation of transcriptional factors, as well as antioxidant enzymes, through epigenetic modification and post-translational modifications. Increased expression and activation of sirtuins has been associated with the suppression of inflammation in several preclinical and clinical studies of inflammatory diseases such as diabetes and with reduced bone resorption in experimental models of osteolytic diseases. Sirtuin 1 (SIRT1) is the most studied deacetylase of the sirtuin family and is involved in biological processes such as senescence and cell differentiation, apoptosis, autophagy, mitochondrial activity, lipid and sugar metabolism, oxidative stress and inflammation. Inhibition of inflammation of gingival tissues and bone resorption in an experimental model of periodontitis was observed in groups treated with resveratrol, a non-specific sirtuin activator, through the reduction of oxidative stress. Additionally, literature data demonstrated that basic periodontal treatment of patients with periodontitis showed an increase in serum levels of SIRT1, indicating the involvement of sirtuin in the pathogenesis of periodontitis. The beneficial effects of sirtuin 1 activation have also been observed in increasing insulin sensitivity and reducing plasma glucose levels in preclinical studies, demonstrating its promising role in modulating type 2 diabetes. Considering the role of sirtuins in inflammation and oxidative stress, several pharmacological activators of these proteins have been developed and therapeutically evaluated in inflammatory and neurodegenerative diseases, and associated with the reduction of signs and symptoms, pre-clinically. Some of these synthetic drugs have demonstrated great potential in increasing the expression of sirtuins, such as SRT1720, when compared to natural activators, such as resveratrol. Considering the protagonism of sirtuins in the regulation of inflammation and oxidative stress, and that SRT1720 has great potential in increasing the expression of SIRT1, in addition to the scarcity of results indicating the role of this activator on SIRT1 applied to the progression of periodontitis, the present study aims to evaluate the role of SRT1720 as an activator of SIRT1 on periodontitis, whether or not associated with type 2 diabetes, in a preclinical study in mice. (AU)