Table 1.
Antioxidant Knockout Mouse Life- and Healthspan.
| Enzyme | Lifespan Effect | Healthspan | References |
|---|---|---|---|
| NNT-/- | nd | Diabetic phenotype and impaired mitochondrial function | [251,252] |
| Gpx1-/- | No change | Reduced allergic asthma, cataracts, hypertension, reperfusion injury-dependent infarct size, AD pathology. | [14,175-182] |
| Gpx2-/- | nd | Increased intestinal cancers, and lung inflammation from acute challenges | [77,183,184] |
| Gpx4-/- | Lethal | Reduced cancer risk. Increased apoptosis-natural selection. | [14,63,99,114,146] |
| Gpx4+/- | ↑7% | Reduced cancer risk. Increased apoptosis-natural selection. | [14,100,110,145] |
| Gpx5-/- | nd | Male infertility. | [76] |
| Trx1-/- | Lethal | Embryonic lethal. | [65] |
| Trx2-/- | Lethal | Embryonic lethal. | [64] |
| Trx2+/- | ↓16% maximal ↓7% median | Increased oxidative damage to macromolecules. Reduced mitochondrial function. | [14] |
| TR1-/- | Lethal | Embryonic lethal. | [66] |
| TR2-/- | Lethal | Embryonic lethal. | [67] |
| Grx1-/- | nd | Lung dysfunction, cataracts, sensitivity to redox cyclers, lens dysfunction, and reduced cardiac hypertrophy. | [79,82-83,88] |
| Grx2-/- | nd | Lung and lens dysfunction. | [87] |
| Prx1-/- | ↓15% | Hemolytic anemia, atherosclerosis, allergic asthma and lung inflammation, and cancer. | [69,98,99] |
| Prx2-/- | ↓15% | Hemolytic anemia, cardiovascular disease, inflammation, senescence, inhibited immunity and enlarged thymus. | [70,96,160-164] |
| Prx3-/- | nd | Increased LPS-induced inflammation. | [185] |
| Prx4-/- | nd | Increased oxidative damage, spermatogenic cell death, and testicular atrophy. | [186] |
| Prx6-/- | nd | Oxidative stimuli sensitive, increased atherosclerosis, and reduced wound healing. | [85,115-116,127,187-190] |
| MSRB-/- | Normal | Increased oxidative damage. | [74] |
| PCat-/- | Normal | Normal. | [14,191] |
| EcSOD-/- | Nd | Hypoxia-induced hypertension/hypertrophy of the heart, renal injury, emphysema/lung sensitivity, and corneal dysfunction. | [75,87,193-198] |
| MnSOD-/- | Lethal | Embryonic lethal. | [62,135-136] |
| MnSOD+/- | Normal | Increased oxidative damage, cancer, and reduced cardiac and mitochondrial function. | [14,72,90-92,137-139] |
| MSRA-/- | Normal | Increased oxidative damage. | [14,71,89,97] |
| CuZnSOD-/- | ↓30% | Hepatocarcinoma, muscle atrophy, bone fragility, axonal degeneration, loss of hearing, b-islet dysfunction (pancreas), reduced wound healing, cataracts, macular degeneration, vascular hypertrophy, and female infertility. | [73,101,103-104, 165-174] |
Antioxidants with changes in life- or healthspan are presented. However, many antioxidant knockout models have not yet been generated, which includes glutathione peroxidase-3, -6, -7 and -8, glutaredoxin-3, -4, -5, -6, -7, and -8, glutathione reductase, peroxiredoxin 5, and thioredoxin reductase 3. nd not determined