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Table 2 Survival data for mice over-expressing or under-expressing antioxidant enzymes

From: A midlife crisis for the mitochondrial free radical theory of aging

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]
  1. Tg = transgenic overexpression.
  2. d = days.
  3. $Sample size of genetically manipulated mice groups. Sample sizes were generally similar or identical to that of WT control groups, except in [31], where N = 119 for control group.
  4. N/A = not available.
  5. *Statistical analysis was not performed. Increased maximum lifespan was observed, but no changes in mean lifespan (Means: Sod2 Tg = 28.8 months versus WT = 27.6 months).
  6. & Max lifespan (90th percentile survival was not provided).
  7. !95th percentile survival.
  8. ^Mean lifespan ± SEM (90th percentile survival was not provided).
  9. C1Control groups consisted of Sod1+/+ and Sod1+/− mice. Values are ± SEM.
  10. PCatalase was targeted to the peroxisome.
  11. mCatalase was targeted to mitochondria.
  12. nCatalase was targeted to the nucleus.
  13. <Two mouse lines were used.
  14. `A slight significant extension of median lifespan was observed in one mouse line (and no extension of maximum lifespan).
  15. >Two separate cohorts of mice were used in the study.
  16. C2Control mice consisted of both WT and Msr+/− mice.
  17. #No change in mean or 90th percentile survival, but P <0.05 for 10th percentile survival.
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Longevity & Healthspan

ISSN: 2046-2395

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