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27
Jan
SIRT1: A Central NAD⁺-Dependent Regulator of Metabolism, Stress Response, and Aging
📅 Published: Jan 2026 🏷️ Category: Protein Research / Molecular Biology
The SIRT1 gene encodes Sirtuin 1, a class III histone deacetylase that functions as a cellular energy status sensor. By linking NAD⁺ metabolism to transcriptional regulation, SIRT1 plays a pivotal role in maintaining cellular homeostasis.
Figure 1: SIRT1-mediated regulatory pathways in cellular adaptation.
🧬 Major Functions and Molecular Mechanisms
Metabolic Regulation
SIRT1 acts as a metabolic master switch, modulating key processes via deacetylation of transcription factors:
- Gluconeogenesis & Glucose homeostasis
- Fatty acid oxidation & Lipid metabolism
- Mitochondrial biogenesis
Anti-Aging & Longevity
Often referred to as the "longevity protein," SIRT1 enhances cellular resilience through:
- Promotion of Genomic Stability
- Enhanced DNA Repair mechanisms
- Regulation of Autophagy
SIRT1 in Disease Contexts
Research indicates that SIRT1 activity is tissue-specific and stage-dependent, playing dual roles in various pathologies:
| Cancer | Acts as both a tumor suppressor (maintaining integrity) and a survival factor for established tumor cells. |
| Neuroge-neration | Impaired activity is linked to Alzheimer’s, exacerbating neuronal dysfunction and oxidative stress. |
| Metabolic Syndrome | Altered signaling contributes to insulin resistance and disrupted lipid balance. |
Research Findings & Experimental Insights
A critical observation in geroscience is that SIRT1 activity declines with age, which correlates with reduced metabolic flexibility. This has led to the intensive study of SIRT1 Activators (STACs).
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Small-molecule intervention: Compounds like Resveratrol and SRT1720 have shown potential in mimicking caloric restriction, effectively extending healthspan in preclinical models.
Biofargo team
