Table 3.
Summary of the effects of metformin and resveratrol on aging-related pathways.
| Oxidative Stress | Protein Homeostasis/Autophagy | Protein Translation | Cell Proliferation | Inflammation | Apoptosis | Anti-Cancer | Neuroprotective | Other | |
|---|---|---|---|---|---|---|---|---|---|
| Resveratrol | |||||||||
| Yeast (2–5 μm) [279] | ↑ yeast survival, ↑ SIRT1 activity | ||||||||
| Kasumi-1 Xenograft Mice (Leukemia Cell Model; 5–20 mg/kg/day, 24 days) [255] | ↑ | ↑ | |||||||
| Kasumi-1 (Leukemia Cell Model; 50 μm, 6 h) [255] | ↑ | ↑ | |||||||
| MCF-10A-Tr xenograft mice (breast cancer animal model (40 mg/kg/day, 30 days) [261] | ↓ | ↓ | ↑ | ↑ | Decreased base excision repair | ||||
| AD Patients (500–2000 mg/day, 52 weeks) [267] | ↓ | ↓ inflammation (IL-8, IL-1R4, IL-12P40, IL-12P70); ↓ permeability to inflammatory agents (↓ MMP9); maintained cerebral spinal fluid proteins | |||||||
| AβPP/PS1 mice (AD animal model; 16 mg/kg/day, 10 months) [292] | Improved synaptic activity (increased synaptophysin) Decreased protein aggregates (BACE, ADAM 10) Regulated by AMPK signalling (Increased AMPK and LKB1 phosphorylation, decreased p53 acetylation) |
||||||||
| TCDD CYP1A induced expression induced in MCF-10A cells (breast cancer cell model; 5–50 μM, 3 days) [293] | ↓ | Decreased oxidative DNA damage (CYP1A1, CYP1B1) | |||||||
| Metformin | |||||||||
| HepG2 cells (liver cancer model; 1–10 mM, 24 h) [294] | ↓ | ↑ | ↑caspase 3, ↑AKT phosphorylation | ||||||
| HepG2 xenograft mice fed with 60% high-fat diet (250 mg/kgbw/day, 4 weeks) [294] | ↓ | ↓Cyclin D1, ↑hypoxia induction and maintenance of micro vessel density: ↑ CA-9, ↓VEGFR | |||||||
| Bone marrow mice -derived macrophages (BMDMs; 2 mM, 24 h) [295] | ↓ | ||||||||
| High fat-fed C57B6L male mice (300 mg/kgbw/day-11 weeks) [295] | ↓ | ↓IL-6, ↓TNF-α | |||||||
MMP9: matrix metallopeptidase 9; BACE: beta-secretase 1; ADAM10: a disintegrin and metalloproteinase domain-containing protein 10; CYP1: cytochrome P450; CA-9: carbonic anhydrase 9; VEGFR: Vascular endothelial growth factor receptor; CK19: cytokeratin-19, α-SMA: alpha smooth muscle actin; GLUT1: glucose transporter 1; GREB1: growth-regulating estrogen receptor binding 1; AP-1: activator protein 1; ARE: antioxidant response elements; SOD: superoxide dismutase; CAT: catalase; GHS: glycinyl-histidinyl-serine; BDNF: brain-derived neurotrophic factor; ER: endoplasmic reticulum.