Ask about this productRelated genes to: SIRT1 antibody
- Gene:
- SIRT1 NIH gene
- Name:
- sirtuin 1
- Previous symbol:
- -
- Synonyms:
- SIR2L1
- Chromosome:
- 10q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 2001-03-20
- Date modifiied:
- 2016-10-05
Related products to: SIRT1 antibody
Related articles to: SIRT1 antibody
- Intervertebral disc degeneration (IDD) is associated with the loss of nucleus pulposus derived mesenchymal stem cell (NP-MSC) function, but the contribution of the mitochondrial unfolded protein response (UPRmt) to this process is not well understood. We found that SIRT1 and the UPRmt-related proteins HSP60, ATF5, and CLPP decreased as degeneration progressed in human disc tissues and primary NP-MSCs. In NP-MSCs exposed to tert-butyl hydroperoxide, metformin increased AMPK phosphorylation and SIRT1 expression, enhanced UPRmt signaling, and reduced apoptosis and senescence. Metformin also improved mitochondrial membrane potential and morphology, lowered reactive oxygen species, restored NAD+ levels, and favored extracellular matrix synthesis. Blocking SIRT1 with EX527 or SIRT1 siRNA weakened UPRmt activation and largely reversed the mitochondrial, cellular, and matrix effects of metformin. In a rat needle-puncture model, intradiscal metformin preserved disc height and T2 signal, reduced histological degeneration, and increased matrix and UPRmt-related protein expression; these effects were diminished by EX527. Together, these results suggest that reduced AMPK/SIRT1/UPRmt activity contributes to NP-MSC dysfunction during IDD and that metformin may slow disc degeneration by restoring this mitochondrial stress response. - Source: PubMed
Publication date: 2026/09/02
Shao ShanzhongHuang ZhiweiLiu JinrunLi JieWang ZiyuYang RuoyuChang ShengxuanBao GuoqingZhu MingGao SongsenZhang ShengquanZhang SumeiLi XiaochuanTao Hui - Circadian rhythm sleep-wake disorders (CRSWDs) arise from alterations in the circadian timing system or from misalignments between endogenous circadian rhythms and environmental or behavioral demands, leading to sleep disturbances and impaired functioning. Diagnosis remains challenging and largely reliant on subjective assessments, highlighting the need for biologically informed markers. Although genetic and epigenetic factors have been implicated in circadian regulation, their contribution to clinically defined CRSWDs has not previously been systematically evaluated across disorders. This systematic review, registered in PROSPERO (ID: 1117673), examined genetic polymorphisms and epigenetic modifications associated with CRSWDs in studies published up to October 2024. Of 871 articles screened, 38 met the inclusion criteria. Delayed sleep-wake phase disorder was investigated in 18 studies (47 %), shift work disorder in 17 studies (45 %), and non-24-h sleep-wake rhythm disorder in eight studies (21 %). Of these, 27 examined genetic variants, predominantly using candidate-gene approaches targeting core clock genes and circadian-related pathways. Ten studies investigated epigenetic alterations, all limited to DNA methylation and conducted exclusively in the context of shift work disorder. Only one study assessed both genetic and epigenetic variations. The findings suggest that genetic variations, particularly in but not limited to core clock genes, are implicated in an increased susceptibility to CRSWDs. In addition, DNA methylation changes in clock genes and genes as MTNR1B, SIRT1, and SLC6A4 may play a role in modulating circadian adaptation, particularly in the context of shift work. However, substantial heterogeneity in phenotypic definitions, study design, and confounder control limits causal inference and cross-disorder comparison. Only five findings met the review-defined evidentiary standards: the functionally validated PER2 S662G and CSNK1D T44A mutations causing familial advanced sleep phase syndrome (FASPS), the independently replicated PER2 p.Val1205Met and RORC rs3828057 associations with delayed sleep-wake phase disorder (DSWPD), and the MTNR1B rs10830963 × night-shift-work interaction associated with prostate cancer risk. All other reported genetic and epigenetic associations remain exploratory. In conclusion, this review identifies a fragmented and uneven evidence base, with major gaps in epigenetic research and integrative genetic-epigenetic analyses across CRSWDs. Epigenetic studies have been conducted almost exclusively in shift work populations, leaving intrinsic CRSWDs largely unexplored. Future research should prioritize longitudinal, genome-wide, and systematically phenotyped studies involving diverse populations and genetic backgrounds. Expanding epigenetic investigation across CRSWD subtypes will be essential to improve the generalizability of findings and advance biomarker development and personalized approaches in circadian and sleep medicine. - Source: PubMed
Publication date: 2026/08/28
Barros Carina NMayer Rose AngelicGarcia-Borreguero DiegoÁlvaro Ana RitaGaspar Laetitia S - Sepsis-associated encephalopathy (SAE) is a devastating condition with high mortality and cognitive sequelae, yet no effective treatments. This study investigates the neuroprotective potential of selective Sirtuin 1 (SIRT1) activation using the synthetic agonist SRT1720 in a male C57BL/6 J murine model of SAE. Transcriptomic profiling of the hippocampus revealed a specific disruption in glutathione and arachidonic acid metabolism pathways, indicating a metabolic priming for ferroptosis. We demonstrate that SIRT1 activation improves survival and ameliorates cognitive deficits by concurrently attenuating hippocampal ferroptosis and neuroinflammation. We observed that this protection was associated with the upregulated protein expression of Nrf2 and GPX4, key regulators of ferroptosis. Mechanistically, SIRT1 activation suppressed hippocampal ferroptosis, marked by reduced lipid peroxidation (ROS and MDA). Concurrently, it attenuated neuroinflammation by suppressing microglial activation and NLRP3 inflammasome activity, thereby decreasing the maturation of proinflammatory cytokines. These findings suggest SIRT1 activation coordinately counteracts both ferroptotic and inflammatory damage in SAE, presenting a compelling therapeutic strategy. - Source: PubMed
Publication date: 2026/09/02
Zhang YueLiu QingzhenZhao HaishuLiu ZhiLiu MengnaNing YaoJi QingZhang Lidong - Aging is multi-causal, yet its molecular hallmarks may converge on a few upstream integrating nodes. We advance the hypothesis that chronic, largely mutation-independent overactivation of the DNA damage response (DDR) is one such node, dysregulating the cell's intact guardian pathways-the tumor-suppressor networks and their negative regulators-to induce senescence, deplete stem-cell pools, and drive inflammaging. Unlike cancer, where mutations inactivate these guardians, aging more often reflects functional dysregulation of wild-type pathways, either chronically overactivated (p53, p16INK4a) or epigenetically silenced (SIRT1, FOXO3, NRF2, Klotho). That the very programs guarding against cancer can, when chronically engaged, come to drive aging we term the guardian paradox. We organize 16 candidate axes-which we term the aging axis-across three evidence tiers, mapped onto the hallmarks of aging, outlining for each a conceptual diagnostic signature and an illustrative restoration strategy, with all numeric biomarker bands and vector details confined to the Supplementary Information as non-clinical placeholders. We set this DDR-integrator hypothesis against mitochondria-, proteostasis-, and reprogramming-first models and pre-specify longitudinal, mediation, and head-to-head tests that could support, demote, or refute it. No integrated human interventional data yet exist; we therefore present a falsifiable research agenda, not a therapeutic protocol. - Source: PubMed
Publication date: 2026/08/31
Sewell Patrick E - Acute ischemic stroke is accompanied by marked peripheral and central immune imbalance, in which disruption of the Th17/Treg axis is considered an important driver of aggravated neuroinflammation and secondary injury, yet the upstream regulatory pathways amenable to intervention remain unclear. We hypothesised that the probiotic Akkermansia muciniphila (AKK) could be linked to post-stroke immune remodelling and neuroprotection by influencing intestinal epithelial signalling. Using a tMCAO mouse model combined with AKK intervention, SIRT1 inhibition, IL-17-deficient conditions, and IL-17 neutralisation/rescue experiments, we systematically assessed intestinal barrier integrity, peripheral and central immune responses, and neurological injury, together with single-cell transcriptomic and ATAC-seq analyses of the Th17/Treg axis. Complementary human and murine intestinal epithelial-T cell co-culture systems and a neuronal OGD model were used for functional mechanistic assessment. AKK was associated with activation of AMPK/SIRT1 signalling, decreased Th17 proportions, increased Treg levels, suppression of IL-17-associated inflammatory responses, and enhancement of IL-10 signalling, thereby improving systemic and intracerebral inflammatory environments. In the neuronal OGD model, IL-17 neutralisation alone provided partial protection, combined AKK and IL-17 blockade further enhanced neuroprotection, and recombinant IL-17 rescue attenuated, but did not fully define, the protective effects of AKK. AKK also protected intestinal barrier integrity, reduced infarct volume, and improved neurological function. Together, these findings support a contributory gut epithelial AMPK/SIRT1-associated immunoregulatory network in which AKK is linked to Th17/Treg immune remodelling and reduced post-stroke neuroinflammation through the gut-immune-brain axis, while IL-17 signalling appears to represent one important component rather than an exclusive pathway. - Source: PubMed
Publication date: 2026/09/02
Zheng JianfengWu ZhihuaLin DuxiangFang MinghuiLin Pengxing