Sirtuins comprise a family of NAD+‑dependent deacetylases that have emerged as important regulators in the pathogenesis of pulmonary disorders. Their enzymatic activity modulates acetylation status of multiple proteins, producing downstream effects on cellular metabolism, stress responses and inflammatory signaling. The pleiotropic roles of sirtuins—spanning oxidative stress control, metabolic homeostasis and inflammation—underpin their increasing recognition in lung disease research. Dysregulated expression or activity of sirtuins has been implicated in several pulmonary pathologies, indicating both mechanistic relevance and potential clinical utility.
A central theme across recent studies is the role of sirtuins in maintaining cellular redox balance and mitochondrial function. Through protein deacetylation, sirtuins influence mitochondrial integrity, bioenergetics and the balance between cell survival and death pathways. These molecular activities link sirtuins to processes that drive tissue injury and repair in the lung. By modulating metabolic pathways and oxidative stress responses, sirtuins can affect inflammatory cascades and the capacity of pulmonary cells to withstand or recover from injurious stimuli.
Evidence summarized in the review highlights contributions of sirtuins to the pathophysiology of several major lung conditions. In chronic obstructive pulmonary disease (COPD), sirtuin-mediated regulation of oxidative stress and cellular survival mechanisms is proposed to influence disease progression. In pulmonary fibrosis, dysregulated sirtuin expression or activity is associated with altered tissue remodeling and metabolic disturbances that may promote fibrogenesis. In lung cancer, sirtuins affect cell survival, death pathways and metabolic reprogramming—mechanisms that can contribute to tumor development and progression. The review emphasizes that sirtuin effects are context dependent and that altered expression or activity can have disease‑specific consequences.
Because sirtuin expression and activity are altered in various lung pathologies, the review highlights their potential utility as diagnostic biomarkers. Changes in sirtuin levels or functional activity could reflect underlying metabolic or stress‑related processes relevant to disease presence, stage or progression. The summary positions sirtuin profiling as a candidate strategy to complement existing diagnostic approaches, while noting that translation from mechanistic observations to validated clinical biomarkers requires additional investigation.
The pleiotropic regulatory roles of sirtuins make them attractive as therapeutic targets. By modulating oxidative stress, mitochondrial function and inflammatory signaling, interventions that influence sirtuin activity may offer avenues for prevention or treatment across different pulmonary diseases. The review synthesizes recent advances that support translational exploration of sirtuin‑directed strategies. It frames sirtuins as dual‑purpose targets: both for direct therapeutic modulation and as parts of broader approaches to restore metabolic and redox homeostasis in injured lung tissue.
The authors conducted a comprehensive literature review of the relationship between sirtuins and lung‑related diseases. Sources were identified by searching PubMed and Web of Science up to May 2025 using the keywords 'sirtuin,' 'SIRTs,' 'lung disease,' and 'pulmonary disease.' The article is presented as a narrative review that synthesizes molecular mechanisms and translational applications reported in the identified literature. It does not present new experimental data; rather, it collates and interprets published findings to inform future research directions.
The review concludes that sirtuins play multifaceted roles in lung biology and disease through regulation of oxidative stress, metabolism and inflammation. Dysregulated sirtuin expression and activity are implicated in COPD, pulmonary fibrosis and lung cancer, supporting investigation of sirtuins as biomarkers and therapeutic targets. The authors suggest that consolidating mechanistic insights could provide a foundation for novel prevention and treatment strategies in pulmonary disease. Specific experimental details, quantitative outcomes and stepwise translational plans were not reported in the abstract; further reading of the full review would be required to access study‑level evidence and proposed interventions.