SIRT1
SIRT1 (sirtuin 1) is an NAD(H)-dependent protein deacetylase that functions as a regulator of cellular stress responses, metabolism, chromatin organization, and tissue repair.
SIRT1 (sirtuin 1) is an NAD(H)-dependent protein deacetylase that functions as a regulator of cellular stress responses, metabolism, chromatin organization, and tissue repair. Recent studies have investigated SIRT1 in diverse contexts, including metabolic dysfunction-associated steatohepatitis, where it formed part of a five-gene lactylation-related expression panel linked to hepatocyte glycolysis, and age-related skeletal regeneration, where reduced SIRT1 was associated with impaired endothelial activity and osteogenesis. Other work has examined SIRT1-dependent regulation of FoxO1a stability, macrophage immunometabolism, mitochondrial and metabolic homeostasis, and heterochromatin-modifying complexes involved in L1 retrotransposon silencing.
SIRT1 is also being explored as a pharmacological target. Experimental studies have assessed small-molecule agonists, including resveratrol and compounds derived from Aspergillus, as well as pyrazolyl thiourea inhibitors of SIRT1 and SIRT2. In disease-oriented models, SIRT1 signaling has been linked to the Keap1/Nrf2 pathway in the control of oxidative stress and ferroptosis, to PGC-1α signaling in macrophage responses, and to responses involving fibrosis, diabetes, wound healing, and cellular senescence. These findings reflect broad interest in SIRT1 as a modulator of stress adaptation and tissue repair, although the cited studies address distinct biological and therapeutic settings.
Where the papers sit
10 papers from the last 6 months study SIRT1 directly · updated from PubMed 1 Nov 2026
Study type 0 clinical trials · 2 human data · 8 preclinical
Themes 3 themes · 1 new direction
-
Cellular Senescence and Aging
Cellular senescence and age-related tissue failure are being linked to loss of SIRT1 activity and impaired stress control. USP25-targeting peptides and sesamin aim to reactivate SIRT1, suppress ferroptosis through Keap1/Nrf2, and improve regeneration or wound repair. SIRT1 also preserves heterochromatin against L1 retrotransposons, connecting its activity to genome stability. Transcriptomic panels extend this work toward biomarkers of disease-dependent aging and hepatocyte metabolic change.
5 papers · 50%
-
Macrophage Stress and Fibrosis
Macrophage immunometabolism links SIRT1 signaling to intestinal inflammation, lung injury and tissue fibrosis. Microbiota-derived 4-HPAA stabilizes SIRT1 and reprograms macrophage activation in Crohn's disease, including barrier and IL10-associated responses. Impaired FoxO1a-Edil3 signaling in aged macrophages worsens lung injury after liver transplantation. Engineered mesenchymal stem cells add integrated stress response control as a complementary route toward fibrosis therapy.
3 papers · 30%
-
Sirtuin Modulator Discovery
Small-molecule control of SIRT1 is splitting into inhibitory and activating strategies rather than a single therapeutic direction. Pyrazolyl thioureas are being developed as SIRT1/SIRT2 inhibitors, with cytotoxic potency and tubulin-associated activity assessed by half-maximal inhibitory concentrations. Aspxanthones A-I provide natural-product SIRT1 agonists from Aspergillus, with hepatocellular carcinoma offering a disease context for evaluation. Selectivity, mechanism and in vivo efficacy remain unresolved.
2 papers · 20%
SIRT1 is presented as a direct suppressor of LINE-1 retrotransposon activity through heterochromatin maintenance
The cellular-senescence and LINE-1 retrotransposon model assumes SIRT1 mainly functions as a disease-modifying metabolic or stress-response regulator, but this study instead identifies it as a genome-stability factor that binds the LINE-1 5′-UTR and stabilizes Lamin B1/KAP1 heterochromatin complexes, increasing H3K9me3, repressing LINE-1 transcription and delaying senescence. This expands SIRT1’s role to direct transposable-element silencing through chromatin organization 42669067Aug.
Papers
The 10 papers from the last 6 months that study SIRT1 directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
Cellular Senescence and Aging (5)
- A Novel Peptide Targeting the USP25-SIRT1 Interaction Activates SIRT1 to Suppress Cell Senescence. Aging cell · 30 Oct 2026 PMID 42963318
- Multi-cohort and single-nucleus transcriptomics identify a five-gene lactylation-related panel and a disease-dependent hepatocyte glycolysis-lactylation-related expression program in metabolic dysfunction-associated steatohepatitis. Functional & integrative genomics · 29 Oct 2026 PMID 42955459
- SIRT1 promotes endothelial activity and osteogenesis in vitro and ameliorates age-related skeletal regeneration defects in vivo. Stem cell reports · 3 Sept 2026 PMID 42692013
- Sesamin Promotes Diabetic Wound Healing by Inhibiting Ferroptosis via the SIRT1/Keap1/Nrf2 Pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 31 Aug 2026 PMID 42671318
- SIRT1 Silences L1 Retrotransposons by Stabilizing Heterochromatin-Modifying Complexes. Aging cell · 30 Aug 2026 PMID 42669067
Macrophage Stress and Fibrosis (3)
- Microbiota-derived 4-HPAA alleviates Crohn's disease by stabilizing SIRT1 and reprogramming macrophage immunometabolism. Apoptosis : an international journal on programmed cell death · 23 Aug 2026 PMID 42634048
- Engineered mesenchymal stem cells regulate integrated stress response for fibrosis therapy. Med (New York, N.Y.) · 12 Aug 2026 PMID 42586072
- FoxO1a-mediated Edil3 transcription is impaired in macrophages and exacerbates lung injury after liver transplantation in the aged microenvironment. Molecular immunology · 28 Jul 2026 PMID 42520358
Sirtuin Modulator Discovery (2)
- Design, Synthesis, and Biological Evaluation of Pyrazolyl Thioureas (PTUs) as SIRT1 and SIRT2 Inhibitors. ChemMedChem · 23 Sept 2026 PMID 42778514
- Discovery of Aspxanthones A-I with SIRT1 agonist activity from Aspergillus sp. TJ507. Bioorganic chemistry · 18 Aug 2026 PMID 42612273
By study type
Human data, design not indexed (2)
- Multi-cohort and single-nucleus transcriptomics identify a five-gene lactylation-related panel and a disease-dependent hepatocyte glycolysis-lactylation-related expression program in metabolic dysfunction-associated steatohepatitis. Functional & integrative genomics · 29 Oct 2026 PMID 42955459
- Discovery of Aspxanthones A-I with SIRT1 agonist activity from Aspergillus sp. TJ507. Bioorganic chemistry · 18 Aug 2026 PMID 42612273
Preclinical: animal, cell and lab studies (8)
- A Novel Peptide Targeting the USP25-SIRT1 Interaction Activates SIRT1 to Suppress Cell Senescence. Aging cell · 30 Oct 2026 PMID 42963318
- Design, Synthesis, and Biological Evaluation of Pyrazolyl Thioureas (PTUs) as SIRT1 and SIRT2 Inhibitors. ChemMedChem · 23 Sept 2026 PMID 42778514
- SIRT1 promotes endothelial activity and osteogenesis in vitro and ameliorates age-related skeletal regeneration defects in vivo. Stem cell reports · 3 Sept 2026 PMID 42692013
- Sesamin Promotes Diabetic Wound Healing by Inhibiting Ferroptosis via the SIRT1/Keap1/Nrf2 Pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 31 Aug 2026 PMID 42671318
- SIRT1 Silences L1 Retrotransposons by Stabilizing Heterochromatin-Modifying Complexes. Aging cell · 30 Aug 2026 PMID 42669067
- Microbiota-derived 4-HPAA alleviates Crohn's disease by stabilizing SIRT1 and reprogramming macrophage immunometabolism. Apoptosis : an international journal on programmed cell death · 23 Aug 2026 PMID 42634048
- Engineered mesenchymal stem cells regulate integrated stress response for fibrosis therapy. Med (New York, N.Y.) · 12 Aug 2026 PMID 42586072
- FoxO1a-mediated Edil3 transcription is impaired in macrophages and exacerbates lung injury after liver transplantation in the aged microenvironment. Molecular immunology · 28 Jul 2026 PMID 42520358
Written from 10 PubMed abstracts, each one listed by PMID above. Published: 2026-10-31. Drafted by language models from published abstracts; not medical advice.