Table 4. Fatty-acid biosynthetic activities that covary with longevity based on lipid-profiles:
Trends with lifespan in inferred activities, transcripts encoding implicated enzymes, and effects of RNAi knock-down
Enzyme Activity (genes responsible) | Correlation to Lifepan Based on Lipid Profiles | Transcript Change in Long-Lived Mutants | Effect of RNAi KD on Peroxide Resistance of N2DRM Adults (P by exp.) | Effect of RNAi KD on Longevity of N2 Adults (P from log-rank tests) |
---|---|---|---|---|
Elongases (elo-1, -2, -5) | ACL, R= −0.87 (P<0.002) Elongation ratios: R= −0.86 à −0.94 (each P<0.002) |
elo-1, ↓ 3.8x elo-2, ↓ 2.6x elo-5, ↓ 13x (MMBC ELO) |
elo-1: ↑14% (0.01, 0.01) elo-2: ↑14% (0.01, 0.01) elo-5: NC (NS) elo-1,elo-2: ↑12% (0.04, 0.03) |
elo-1: ↑11% (0.02) elo-2: ↑8% (0.04) elo-5: NC (NS) elo-1 + elo-2: ↑15% (0.004) |
Δ6 desaturase (fat-3) | R= −0.75 (P<0.02) | NC | fat-3, NC (NS) | fat-3: ↑≥10% [10,12] (not retested here due to unaltered H2O2-survival) |
Δ5 desaturase (fat-4) | R=−0.71 (P<0.03) | ↓ 2 - 7x in age-1(mg44) ↑ 1.4-2x in age-1(hx546) ↑ 1.5-3x in daf-2(e1370) |
fat-4, ↑60% (1E-6, 1E-6) |
fat-4, ↑ 25% (4E-5) elo-1 + fat-4: ↑12% (differs from FV or fat-4, P≈0.01) |
Δ9 desaturases (fat-5, -6, -7) | R= +0.94 (P<5E-5) for 3 Δ9 desaturases combined |
fat-5, NC fat-6 ↑ 2.0-2.2x fat-7 ↑ 1.5-1.8x |
fat-5: NC (NS) fat-6: ↑24% (1E-5, 1E-5) fat-7: NC (NS) |
fat-5: NC (NS) fat-6: ↓9% (NS) fat-7: ↓8% (NS) |
NC: no change; NS, not significant. Life extension by fat-4 RNAi was also reported previously as ~25% [10]. Significance of survival differences was assessed by Cox-Mantel log-rank test, relative to Feeding Vector (FV) control plasmid unless otherwise indicated.