Introduction
Review
Predictions based on the MFRTA
The role of oxygen in the MFRTA
Reactive oxygen species production
Species investigated | Tissue | Metabolic substrate(s) used | Relationship to MLSP* | Reference |
---|---|---|---|---|
Fruit fly Drosophila melanogaster | Whole body | Pyruvate + proline | Weak correlation | [23] |
Glycerol-3-phosphate | Weak correlation males only | |||
Glycerol-3-phosphate + rotenone | ||||
No correlation | ||||
Naked mole rat Heterocephalus glaber, Damara mole rat Cryptomas damarensis, Guinea pig Cavia porcellus, laboratory mouse Mus musculus | Vascular tissue | Succinate ± rotenone | No correlation | [24] |
Domestic pigeon Columba livia, Japanese quail Coturnix japonica, laboratory rat Rattus norvegicus | Isolated heart mitochondria | Succinate | Negative correlation | [25] |
Succinate + rotenone | No correlation | |||
Laboratory mouse Mus musculus, house sparrow Passer domesticus | Isolated liver mitochondria | Glutamate + malate | No correlation when standardized to total O2 consumption | [26] |
Laboratory mouse Mus musculus, house sparrow Passer domesticus | Isolated mitochondria from pectoralis (sparrow) or hindlimb (rat) muscle | Multiple substrates | No correlation when O2 consumption rates considered | [28] |
Pigeon (species not indicated), rat (Rattus norvegicus) | Isolated mitochondria from heart, muscle and liver | Pyruvate + malate | Higher rates in pigeon muscle | [27] |
Succinate | ||||
Higher rates in rat heart | ||||
Succinate + rotenone | ||||
Higher rates in rat heart | ||||
Little brown bat Myotis lucifugus, short-tailed shrew Blarina brevicauda, white-footed mouse Peromyscus leucopus | Isolated mitochondria from brain, heart, kidney | Not given | No correlation | [29] |
Little brown bat Myotis lucifugus, laboratory mouse Mus musculus | Isolated liver mitochondria | Glutamate + malate | Negative correlation | [26] |
12 mammalian and avian species | Isolated heart mitochondria | Succinate | Negative correlation | [25] |
Succinate + rotenone | ||||
No correlation | ||||
No correlation | ||||
Pyruvate + malate ± rotentone |
Antioxidants
Genotype | Strain |
N
$
| 90th percentile survival (95% C.I.) [versus WT Control] | Survivorship effect? (P>0.05) | Reference |
---|---|---|---|---|---|
Single gene manipulations:
| |||||
Mn superoxide dismutase
| |||||
Sod2
Tg
| C57BL/6 (males) | 50 | 1,165 d (1,092 to 1,245) [versus 1,128 d (1,080 to 1,206)] | No | [49] |
Sod2
Tg
| Not indicated | 24 | N/A - 43.0 months [versus 36.5 months] and | N/A* | [52] |
Sod2
+/−
| C57BL/6 (females) | 70 | 1,027 d (1,044 to 1,154) [versus 1,034 d (1,002 to 1,099)] | No | [53] |
CuZn superoxide dismutase
| |||||
Sod1
Tg
| C57BL/6 (male) | 44 | 1,121 d [versus 1,090 d] | No | [50] |
Sod1
Tg (homozygous)
| CD1 | 119 | 30 months [versus 31 months]! | No | [54] |
Sod1
Tg (hemizygous)
| CD1 | 200 | 31 months [versus 31 months]! | No | [54] |
Sod1
−/−
| C57BL/6 | 10 | 762 d (761 to 767) [versus 1,076 d (1,035 to 1,298)] | Yes - decrease in mean lifespan | [51] |
Sod1
+/−
| C57BL/6 | 12 | N/A - 28.7 ± 1.3 months [versus 29.8 ± 2.1 months]^ | No | [55] |
Sod1
−/−
| C57BL/6 | 18 | N/A - 20.8 ± 0.7 months [versus 29.8 ± 2.1 monthsC1]^ | Yes | [55] |
Catalase
| |||||
Cat
Tg
| C57BL/6 (male) | 44 | 1,099 d [versus 1,090 d] | No | [50] |
Cat
Tg
p
| C57BL/6 < | 44 | N/A (only a survivor curve was given - clear values not provided) | No’ | [56] |
Cat
Tg
m
| C57BL/6 < | 62 | N/A | Yes - increased median and maximum lifespan | [56] |
Cat
Tg
n
| C57BL/6 < | 78 | N/A | No | [56] |
Glutathione peroxidase 4
| |||||
Gpx4
Tg
| C57BL/6 (males) | 18 | 1,072 d (1,062 to 1,080) [versus 1,106 d (1,026 to 1,161)] | No | [51] |
Gpx4
+/−
| C57BL/6 (females) | 50 | 1,126 ± 20 d [versus 1,145 ± 9 d] | Yes - significant increase in mean lifespan only | [57] |
Glutathione peroxidase 1
| |||||
Gpx1
−/−
| C57BL/6 (females) | 59 | 1,063 d (1,031 to 1,183) [versus 1,091 d (1,040 to 1,188)] | No | [58] |
Thioredoxin 1
| |||||
Trx1
Tg
| C57BL/6 (males)> | 41 | 1,134 d [versus 1,159 d] | No# | [59] |
Trx1
Tg
| C57BL/6 (males)> | 60 | 1,151 d [versus 1,143 d] | No# | [59] |
Trx1
Tg
| C57BL/6 (females) | 40 | 1,152 d [versus 1,230 d] | No | [59] |
Thioredoxin 2
| |||||
Trx2
+/−
| Mix of C57BL/6 J & 129 (females) | 26 | 1,059 d (1,020 to 1,139) [versus 1,186 d (1,086 to 1,359)] | No | [51] |
Methionine sulfoxide reductase
| |||||
MsrA
−/−
| Mix of C57BL/6 J & 129 (males) | 25 | 1,157 d (1,105 to 1,203) [versus 1,140 d (1,092 to 1,204)]C2 | No | [60] |
MsrA
−/−
| C57BL/6 J | 17 | N/A - 409 ± 33 d [versus 680 ± 71 d]^ | Yes - increase in mean lifespan | [61] |
MsrA
+/−
| C57BL/6 J | 8 | N/A - 672 ± 80 d [versus 680 ± 71 d]^ | No | [61] |
Multiple gene manipulations:
| |||||
Sod1
Tg /
Sod2
Tg
| C57BL/6 (males) | 54 | 1,075 d [versus 1,090 d] | No | [50] |
S
od1
−/−
/ S
od2
+/−
| C57BL/6 | 11 | 886 d (817 to 883) [versus 1,076 d (1,035 to 1,298)] | Yes | [51] |
Sod1
Tg /
Cat
Tg
| C57BL/6 (males) | 47 | 1,098 d [versus 1,090 d] | No | [50] |
Sod2
+/−
/
Gpx4
+/−
| C57BL/6 | 11 | 1,025 d (938 to 1,099) [versus 1,076 d (1,035 to 1,298)] | No | [51] |
Sod2
+/−
/ Gpx1
+/−
| C57BL/6 | 25 | 1,057 d (1,027 to 1,298) [versus 1,091 d (1,040 to 1,188)] | No | [58] |
Sod2
+/−
/Gpx1
−/−
| C57BL/6 | 33 | 1,121 d (1,069 to 1,248) [versus 1,091 d (1,040 to 1,188)] | No | [58] |
Sod1
−/−
/ Gpx1
−/−
| C57BL/6 (males) | 11 | 828 d (799 to 868) [versus 1,076 d (1,035 to 1,298)] | Yes - decrease in mean lifespan | [51] |
Sod1
−/−
/
Gpx4
+/−
| C57BL/6 (males) | 16 | 866 d (817 to 883 [versus 1,076 d (1,035 to 1,298)] | Yes - decrease in mean and median lifespan | [51] |
Gpx1
-/
/
Gpx4
+/−
| C57BL/6 | 40 | 1,124 d (1,086 to 1,359) [versus 1,076 d (1,035 to 1,298)] | No | [51] |