Caloric restriction (CR) is an important means to delay senescence, and glucose restriction is one of the measures to achieve CR. On the basis of our previous work and bioinformatics analysis, we hypothesized that glucose restriction can up-regulate autophagy, inhibit senescence and promote proliferation via the AMPK/SIRT1-FOXA3-Beclin1 pathway in human umbilical vein endothelial cells (HUVECs). We found that compared with 5.5 mmol/L and 25 mmol/L glucose, 2.5 mmol/L glucose restriction significantly reduced senescence, enhanced autophagy, increased migration speed, relieved G₀/G₁ phase arrest and enhanced proliferation of HUVECs. Furthermore, glucose restriction up-regulated AMPKα1, SIRT1, FOXA3 and Beclin1 expression in HUVECs. Additionally, we demonstrated that AMPKα1 phosphorylated FOXA3 at S170 and S305 in the cytoplasm and promoted FOXA3 nuclear translocation under glucose restriction. FOXA3 in the nucleus was deacetylated by SIRT1 at K214 and K221. Deacetylated FOXA3 specifically bound to +109 C in the Beclin1 transcriptional regulatory region, and significantly enhanced Beclin1 transcription and expression. siRNA knock down of AMPKα1, SIRT1, FOXA3 or Beclin1 expression impaired the glucose restriction-induced inhibition of senescence, enhanced autophagy, increased migration, and induced proliferation of HUVECs. This study confirmed that glucose restriction can enhance autophagy, inhibit senescence, and enhance proliferation of HUVECs through the AMPK/SIRT1-FOXA3-Beclin1 pathway.

热量限制（CR）是延缓衰老的重要手段，而葡萄糖限制是实现CR的措施之一。根据我们之前的工作和生物信息学分析，我们假设葡萄糖限制可以通过AMPK / SIRT1-FOXA3-Beclin1途径在人脐静脉内皮细胞（HUVEC）中上调自噬，抑制衰老并促进增殖。我们发现，与5.5 mmol / L和25 mmol / L葡萄糖相比，2.5 mmol / L葡萄糖限制显着降低了衰老，增强了自噬，提高了迁移速度，减轻了G ₀ / G ₁停滞和增强HUVEC的增殖。此外，葡萄糖限制上调了HUVECs中AMPKα1，SIRT1，FOXA3和Beclin1的表达。另外，我们证明了AMPKα1在细胞质中的S170和S305处磷酸化了FOXA3，并在葡萄糖限制下促进了FOXA3的核转运。SIRT1在K214和K221处使核中的FOXA3脱乙酰化。脱乙酰化的FOXA3与Beclin1转录调节区域中的+109 C特异性结合，并显着增强Beclin1转录和表达。siRNA敲低AMPKα1，SIRT1，FOXA3或Beclin1的表达会损害葡萄糖限制诱导的衰老抑制，自噬，迁移增加和诱导HUVEC增殖。这项研究证实葡萄糖限制可以通过AMPK / SIRT1-FOXA3-Beclin1途径增强自噬，抑制衰老并增强HUVEC的增殖。