Sirtuins are NAD-dependent protein deacylases and key metabolic regulators, coupling the cellular energy state with selective lysine deacylation to regulate many downstream cellular processes. Humans encode seven sirtuin isoforms (Sirt1-7) with diverse subcellular localization and deacylase targets. Sirtuins are considered protective anti-aging proteins since increased sirtuin activity is canonically associated with lifespan extension and decreased activity with developing aging-related diseases. However, sirtuins can also assume detrimental cellular roles where increased activity contributes to pathophysiology. Modulation of sirtuin activity by activators and inhibitors thus holds substantial potential for defining the cellular roles of sirtuins in health and disease and developing therapeutics. Instead of being comprehensive, this review discusses the well-characterized sirtuin activators and inhibitors available to date, particularly those with demonstrated selectivity, potency, and cellular activity. This review also provides recommendations regarding the best-in-class sirtuin activators and inhibitors for practical research as sirtuin modulator discovery and refinement evolve.
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http://dx.doi.org/10.3390/molecules29051185 | DOI Listing |
iScience
January 2025
CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, University Lyon, F-69007 Lyon, France.
Alpha-kinase 1 (ALPK1) is an immune receptor sensing the bacterial nucleotide sugar ADP-heptose. ALPK1 phosphorylates TIFA leading to its oligomerization and downstream NF-κB activation. Specific mutations in are associated with an autoinflammatory syndrome termed ROSAH and with spiradenoma (skin cancers with sweat gland differentiation).
View Article and Find Full Text PDFJ Inflamm Res
January 2025
Precision Medicine Laboratory, School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, People's Republic of China.
Ovarian cancer (OC) remains one of the most lethal gynecological malignancies, largely due to its late-stage diagnosis and high recurrence rates. Chronic inflammation is a critical driver of OC progression, contributing to immune evasion, tumor growth, and metastasis. Inflammatory cytokines, including IL-6, TNF-α, and IL-8, as well as key signaling pathways such as nuclear factor kappa B (NF-kB) and signal transducer and activator of transcription 3 (STAT3), are upregulated in OC, promoting a tumor-promoting environment.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Pain Management, The State Key Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Background: The nod-like receptor family pyrin domain-containing 3 (NLRP3) has been implicated in various skin diseases. However, its role in mediating 2, 4-dinitrofluorobenzene (DNFB)-induced chronic itch remains unclear.
Methods: Widetype () and deletion ( )mice, the expression of transient receptor potential (TRP) ankyrin 1 (TRPA1) inhibitor or recombinant mice interleukin-18 (IL-18) were used to establish and evaluate the severity of DNFB-mediated chronic itch.
Front Immunol
January 2025
Acupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease. Patients with UC typically exhibit disruption of the Treg/Th17 immune axis, but its exact mechanism is still unclear.
Methods: This study first analyzed RNA- seq data from public databases of humans and mice, and cytology experiments were conducted to induce or inhibit the expression of SIRT1.
Front Immunol
January 2025
Xin'an Medicine Research Center, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, China.
Background: is a differentially expressed gene (DEG) between M1 and M2 macrophages. This study explained why it causes opposite effects in different circumstances.
Methods: Gene expression profiles of various cell subsets were compared by mining a public database.
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