The role of Sirtuin 1 and its activators in age-related lung disease.

Aging is a major driving factor in lung diseases. Age-related lung disease is associated with downregulated expression of SIRT1, an NAD+-dependent deacetylase that regulates inflammation and stress resistance. SIRT1 acts by inducing the deacetylation of various substrates and regulates several mechanisms that relate to lung aging, such as genomic instability, lung stem cell exhaustion, mitochondrial dysfunction, telomere shortening, and immune senescence. Chinese herbal medicines have many biological activities, exerting anti-inflammatory, anti-oxidation, anti-tumor, and immune regulatory effects. Recent studies have confirmed that many Chinese herbs have the effect of activating SIRT1. Therefore, we reviewed the mechanism of SIRT1 in age-related lung disease and explored the potential roles of Chinese herbs as SIRT1 activators in the treatment of age-related lung disease.

Bergenin ameliorates airway inflammation and remodeling in asthma by activating SIRT1 in macrophages to regulate the NF-κB pathway.

Airway inflammation and remodeling are critical pathological changes in asthma, and macrophage activation plays a vital role in this process. Sirtuin 1 (SIRT1) reduces airway inflammation by affecting macrophages in asthma. This study aimed to investigate the potential benefit and underlying mechanism of the SIRT1 agonist bergenin as a treatment for asthma. We performed in vivo and in vitro experiments by establishing a Sirt1 fl/fl -LysMcre mouse asthma model and using the alveolar macrophage-like cell line MH-S, respectively. Our results show that Sirt1 fl/fl -LysMcre asthmatic mice exhibited more severe airway inflammation and airway remodeling than wild-type mice. As an activator of SIRT1, bergenin attenuated asthmatic airway pathology and reduced production of interleukins 1ß, IL-5, IL-6, and matrix metalloproteinase 9 (MMP-9) in wild-type asthmatic mice. However, the therapeutic effects of bergenin were significantly attenuated in Sirt1 fl/fl -LysMcre asthmatic mice or following coadministration with the SIRT1 inhibitor EX-527. Further experiments showed that activation of SIRT1 by bergenin deacetylates nuclear factor κB and hinders its nuclear translocation, thereby affecting IL-1ß, IL-5, IL-6, and MMP-9 production by regulating transcriptional activity. Our study suggests that bergenin can improve asthma-induced airway inflammation and remodeling by activating SIRT1 in macrophages.