Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age
Abstract
:1. Introduction
2. Results
2.1. Effect of Aging and Methionine Restriction in the Cerebellum Lipidome
2.2. Effect of Aging and Methionine Restriction in the Frontal Cortex Lipidome
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Animals and Diets
4.3. Sample Homogenization
4.4. Untargeted Lipidomic Analysis
4.5. Fatty Acid Profile
4.6. Markers of Mitochondrial Stress and Tissue Protein Damage
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Class | ID | Post Hoc | Biological Meaning (Biomarker) |
---|---|---|---|
GL | TG (52:0) a | A < R | |
TG (47:0) b | A < R | ||
TG-O (54:1) b | Ag, R < A | aging | |
TG-O (60:1) b | Ag, R < A | aging | |
TG-O (47:0) b | A, Ag < R | MetR | |
TG-O (56:1) b | Ag < R, A | healthy aging | |
GP | PS (36:1) a | A < R | |
PE-P (38:4) a | A < R | ||
PG-P (38:5) b | A < Ag, R | aging | |
PE-P (40:4)/PE-O (40:5) a | Ag, R < A | aging | |
PA (44:7) a | A < Ag, R | aging | |
PE-Nme (36:6) b | A < Ag, R | aging | |
PC-O (38:4)/PC-P (38:3) b | A < Ag, R | aging | |
PE-Nme (34:3)/PE-NMe2 (33:3)/PC (32:3)/PE (35:3) b | A, Ag < R | MetR | |
PC (36:4)/PC-O (35:4) a | A, Ag < R | MetR | |
PS (40:4) a | Ag < R, A | healthy aging | |
SP | Cer (34:1) a | Ag < R, A | healthy aging |
Cer (38:4) a | A < Ag, R | aging | |
SM (33:1) b | A < Ag, R | aging | |
Ganglioside GA2 (44:1) b | Ag, R < A | aging | |
N-(2R-Hydroxyhexadecanoyl)-2S-amino-9-methyl-4E,8E-octadecadiene-1,3R-diol b | A < Ag, R | aging | |
SL | CE (22:4) b | Ag, R < A | aging |
cholest-5-en-3b-yl (11Z,14Z-eicosadienoate) c | A, Ag < R | MetR | |
CE (xx) | Ag < R, A | healthy aging |
Fatty Acid | Adult | Aged | Aged+MetR |
---|---|---|---|
14:0 | 0.26 ± 0.00 | 0.29 ± 0.01 a,* | 0.32 ± 0.01 a,*** |
16:0 | 17.93 ± 0.16 | 18.00 ± 0.04 | 17.83 ± 0.14 |
16:1n-7 | 0.38 ± 0.01 | 0.41 ± 0.02 | 0.40 ± 0.01 |
18:0 | 17.63 ± 0.06 | 17.70 ± 0.09 | 17.66 ± 0.08 |
18:1n-9 | 26.00 ± 0.14 | 26.53 ± 0.25 | 26.74 ± 0.21 a,* |
18:2n-6 | 1.14 ± 0.02 | 1.19 ± 0.04 | 1.37 ± 0.05 a,***; b,** |
18:3n-6 | 0.02 ± 0.00 | 0.02 ± 0.00 | 0.01 ± 0.00 |
18:3n-3 | 0.02 ± 0.00 | 0.02 ± 0.00 | 0.01 ± 0.00 a,* |
18:4n-3 | 0.03 ± 0.00 | 0.03 ± 0.00 | 0.03 ± 0.00 |
20:0 | 0.70 ± 0.04 | 0.83 ± 0.01 a,* | 0.79 ± 0.04 |
20:1n-9 | 4.06 ± 0.14 | 4.48 ± 0.07 a,* | 4.49 ± 0.10 a,* |
20:2n-6 | 0.33 ± 0.01 | 0.29 ± 0.01 a,** | 0.30 ± 0.01 |
20:3n-6 | 0.31 ± 0.01 | 0.30 ± 0.01 | 0.32 ± 0.01 |
20:4n-6 | 7.69 ± 0.08 | 7.27 ± 0.09 a,** | 7.36 ± 0.09 a,* |
20:5n-3 | 0.04 ± 0.00 | 0.04 ± 0.00 a,* | 0.04 ± 0.00 |
22:0 | 0.74 ± 0.02 | 0.75 ± 0.01 | 0.76 ± 0.02 |
22:1n-9 | 1.08 ± 0.09 | 1.01 ± 0.02 | 1.03 ± 0.03 |
22:4n-6 | 2.60 ± 0.03 | 2.22 ± 0.05 a,*** | 2.22 ± 0.05 a,*** |
22:5n-6 | 0.43 ± 0.03 | 0.45 ± 0.03 | 0.41 ± 0.03 |
22:5n-3 | 0.14 ± 0.00 | 0.14 ± 0.01 | 0.12 ± 0.00 |
22:6n-3 | 13.43 ± 0.12 | 12.96 ± 0.14 | 12.89 ± 0.17 a,* |
24:0 | 1.11 ± 0.05 | 1.00 ± 0.02 | 1.03 ± 0.02 |
24:1 | 2.26 ± 0.05 | 2.54 ± 0.10 | 2.41 ± 0.08 |
24:5n-3 | 0.04 ± 0.00 | 0.04 ± 0.00 | 0.04 ± 0.00 |
24:6n-3 | 1.31 ± 0.04 | 1.38 ± 0.03 | 1.45 ± 0.03 a,* |
Fatty Acid Index | Adult | Aged | Aged+MetR |
---|---|---|---|
ACL | 18.91 ± 0.01 | 18.75 ± 0.08 | 18.89 ± 0.00 |
SFA | 38.37 ± 0.17 | 38.35 ± 0.16 | 38.24 ± 0.14 |
UFA | 61.52 ± 0.15 | 61.41 ± 0.12 | 61.58 ± 0.20 |
MUFA | 33.64 ± 0.35 | 35.27 ± 0.16 a,** | 35.01 ± 0.33 a,** |
PUFA | 27.53 ± 0.19 | 26.05 ± 0.19 a,*** | 26.57 ± 0.16 a,** |
PUFAn-3 | 15.00 ± 0.10 | 14.59 ± 0.16 | 14.58 ± 0.15 |
PUFAn-6 | 12.53 ± 0.12 | 11.65 ± 0.12 a,*** | 11.99 ± 0.15 a,* |
DBI | 170.56 ± 0.96 | 165.22 ± 0.86 a,*** | 166.91 ± 0.64 a,* |
PI | 166.05 ± 1.14 | 158.66 ± 1.08 a,*** | 160.06 ± 1.27 a,** |
D9D (n-7) | 0.02 ± 0.00 | 0.02 ± 0.00 | 0.02 ± 0.00 |
D9D (n-9) | 1.47 ± 0.01 | 1.50 ± 0.02 | 1.51 ± 0.02 |
D5D (n-6) | 24.65 ± 0.42 | 24.45 ± 0.73 | 23.36 ± 0.63 |
D6D (n-3) (a) | 1.84 ± 0.05 | 1.83 ± 0.08 | 1.99 ± 0.09 |
D6D (n-3) (b) | 31.22 ± 1.76 | 34.49 ± 1.58 | 36.78 ± 1.87 |
Elovl3 (n-9) | 0.16 ± 0.01 | 0.17 ± 0.00 | 0.17 ± 0.00 |
Elovl6 | 0.98 ± 0.01 | 0.98 ± 0.00 | 0.99 ± 0.01 |
Elovl1-3-7 (a) | 0.04 ± 0.00 | 0.05 ± 0.00 a,* | 0.04 ± 0.00 |
Elovl1-3-7 (b) | 1.09 ± 0.05 | 0.91 ± 0.01 a,** | 0.97 ± 0.04 |
Elovl1-3-7 (c) | 1.49 ± 0.06 | 1.34 ± 0.03 a,* | 1.33 ± 0.01 a,* |
Elovl5 (n-6) | 0.29 ± 0.01 | 0.23 ± 0.00 a,*** | 0.22 ± 0.00 a,*** |
Elovl2-5 (n-6) | 0.34 ± 0.00 | 0.31 ± 0.01 a,*** | 0.30 ± 0.01 a,*** |
Elovl2-5 (n-3) | 3.76 ± 0.07 | 3.30 ± 0.18 a,* | 3.11 ± 0.12 a,** |
Elovl2 (n-3) | 0.31 ± 0.01 | 0.30 ± 0.01 | 0.34 ± 0.01 |
Peroxisomal β-oxidation | 10.39 ± 0.44 | 9.42 ± 0.15 | 8.91 ± 0.28 a,** |
Damage Marker | Adult | Aged | Aged+MetR |
---|---|---|---|
GSA | 5013.14 ± 144.38 | 4376.78 ± 116.83 a,* | 4410.87 ± 77.14 a,* |
CEL | 579.82 ± 39.05 | 725.42 ± 93.56 | 660.52 ± 37.93 |
CML | 1408.30 ± 59.83 | 1387.38 ± 105.08 | 1302.08 ± 43.07 |
MDAL | 196.20 ± 8.66 | 179.29 ± 5.01 | 195.32 ± 8.66 |
2-SC | 39.79 ± 4.34 | 26.85 ± 1.80 a,* | 26.79 ± 2.27 a,* |
Class | ID | Post Hoc | Biological Meaning (Biomarker) |
---|---|---|---|
FA | 12-hydroxyheptadecanoic acid b | Ag, R < A | aging |
GL | TG (50:0) b | R < A | |
TG (48:1) b | Ag, R < A | aging | |
TG (54:6) b | Ag, R < A | aging | |
TG (50:1) b | Ag, R < A | aging | |
TG (64:14) b | A < Ag, R | aging | |
TG (47:0) b | Ag < R | ||
TG-O (58:10) a | R < Ag | ||
DG (40:3) b | R < Ag | ||
TG (64:14) a | A, Ag < R | MetR | |
TG-O (60:9) b | R, A < Ag | healthy aging | |
TG (62:12) b | Ag < R, A | healthy aging | |
GP | PE (36:1) a | R < A | |
PE (39:5)/PE-P (40:4) a | R < A | ||
PC (36:2) a | Ag, R < A | aging | |
PE-P (40:6) a | Ag, R < A | aging | |
PE-P (38:6) a | Ag, R < A | aging | |
PE-NMe (34:3)/PE (35:4)/PC (32:3) b | A, Ag < R | MetR | |
PE-NMe (34:3)/PC (32:3) b | A, Ag < R | MetR | |
PA (44:7) a | A, Ag < R | MetR | |
PE (40:4) a | R < A, Ag | MetR | |
PE (38:1) a | R < A, Ag | MetR | |
PE-P (38:1) a | R < A, Ag | MetR | |
PI (38:4) a | Ag < R, A | healthy aging | |
PI (38:5) a | Ag < A | ||
PG (34:1) a | Ag < R, A | healthy aging | |
PL | Dolichol-20 d | A < Ag, R | aging |
SP | Cer (36:1) a | Ag < A | |
LacCer (34:2)/GalCer (44:2) b | R < A, Ag | MetR | |
Cer (36:1) b | R < A, Ag | MetR | |
N-(2R-Hydroxyhexadecanoyl)-2S-amino-9-methyl-4E,8E-octadecadiene-1,3R-diol b | R < A, Ag | MetR | |
Cer (34:1) c | R < A, Ag | MetR | |
SL | CE (20:4) b | A < Ag, R | aging |
CE (5:0) b | A, Ag < R | MetR |
Fatty Acid | Adult | Aged | Aged+MetR |
---|---|---|---|
14:0 | 0.92 ± 0.02 | 0.91 ± 0.01 | 0.92 ± 0.02 |
16:0 | 29.03 ± 0.014 | 29.31 ± 0.26 | 28.83 ± 0.12 |
16:1n-7 | 0.54 ± 0.02 | 0.56 ± 0.03 | 0.52 ± 0.01 |
18:0 | 24.17 ± 0.23 | 24.19 ± 0.11 | 24.20 ± 0.10 |
18:1n-9 | 19.71 ± 0.26 | 19.18 ± 0.19 | 19.47 ± 0.20 |
18:2n-6 | 0.94 ± 0.02 | 1.00 ± 0.03 | 1.06 ± 0.06 |
18:3n-6 | 0.03 ± 0.00 | 0.04 ± 0.00 | 0.04 ± 0.00 |
18:3n-3 | 0.03 ± 0.00 | 0.04 ± 0.00 | 0.04 ± 0.00 |
18:4n-3 | 0.04 ± 0.00 | 0.04 ± 0.00 | 0.05 ± 0.00 |
20:0 | 0.18 ± 0.01 | 0.18 ± 0.01 | 0.19 ± 0.01 |
20:1n-9 | 0.71 ± 0.04 | 0.68 ± 0.04 | 0.71 ± 0.04 |
20:2n-6 | 0.11 ± 0.00 | 0.11 ± 0.00 | 0.12 ± 0.01 |
20:3n-6 | 0.20 ± 0.00 | 0.22 ± 0.01 | 0.24 ± 0.01 a,*** |
20:4n-6 | 10.20 ± 0.26 | 10.49 ± 0.11 | 10.53 ± 0.18 |
20:5n-3 | 0.04 ± 0.00 | 0.04 ± 0.00 | 0.04 ± 0.00 |
22:0 | 0.18 ± 0.01 | 0.16 ± 0.01 | 0.16 ± 0.00 |
22:1n-9 | 0.57 ± 0.05 | 0.58 ± 0.03 | 0.62 ± 0.02 |
22:4n-6 | 2.38 ± 0.08 | 2.35 ± 0.05 | 2.35 ± 0.07 |
22:5n-6 | 0.80 ± 0.07 | 0.99 ± 0.09 | 0.91 ± 0.08 |
22:5n-3 | 0.09 ± 0.00 | 0.10 ± 0.00 | 0.10 ± 0.00 |
22:6n-3 | 7.95 ± 0.25 | 8.31 ± 0.19 | 8.36 ± 0.17 |
24:0 | 0.15 ± 0.01 | 0.17 ± 0.00 | 0.17 ± 0.01 |
24:1 | 0.17 ± 0.01 | 0.14 ± 0.01 | 0.14 ± 0.01 |
24:5n-3 | 0.04 ± 0.00 | 0.04 ± 0.00 | 0.04 ± 0.00 |
24:6n-3 | 0.19 ± 0.01 | 0.15 ± 0.00 a,* | 0.15 ± 0.01 a,** |
Fatty Acid Index | Adult | Aged | Aged+MetR |
---|---|---|---|
ACL | 18.12 ± 0.01 | 18.13 ± 0.01 | 18.12 ± 0.02 |
SFA | 54.63 ± 0.19 | 54.89 ± 0.35 | 54.45 ± 0.15 |
UFA | 44.67 ± 0.58 | 45.09 ± 0.34 | 45.43 ± 0.16 |
MUFA | 21.77 ± 0.33 | 21.15 ± 0.25 | 21.40 ± 0.27 |
PUFA | 23.05 ± 0.58 | 23.94 ± 0.30 | 24.03 ± 0.33 |
PUFAn-3 | 8.57 ± 0.17 | 8.74 ± 0.18 | 8.78 ± 0.17 |
PUFAn-6 | 14.67 ± 0.36 | 15.20 ± 0.19 | 15.25 ± 0.27 |
DBI | 128.67 ± 2.74 | 132.49 ± 1.52 | 132.94 ± 1.43 |
PI | 123.50 ± 3.31 | 128.55 ± 1.91 | 128.69 ± 1.97 |
D9D (n-7) | 0.02 ± 0.00 | 0.02 ± 0.00 | 0.02 ± 0.00 |
D9D (n-9) | 0.82 ± 0.01 | 0.79 ± 0.01 | 0.80 ± 0.01 |
D5D (n-6) | 49.68 ± 0.31 | 47.75 ± 2.05 | 43.81 ± 1.12 a,* |
D6D (n-3) (a) | 1.03 ± 0.16 | 1.10 ± 0.07 | 1.18 ± 0.06 |
D6D (n-3) (b) | 5.10 ± 0.55 | 3.88 ± 0.34 a,* | 3.86 ± 0.36 |
Elovl3 (n-9) | 0.04 ± 0.00 | 0.04 ± 0.00 | 0.04 ± 0.00 |
Elovl6 | 0.83 ± 0.01 | 0.83 ± 0.00 | 0.84 ± 0.01 |
Elovl1-3-7 (a) | 0.01 ± 0.00 | 0.01 ± 0.00 | 0.01 ± 0.00 |
Elovl1-3-7 (b) | 1.02 ± 0.04 | 0.86 ± 0.03 a,** | 0.86 ± 0.02 a,** |
Elovl1-3-7 (c) | 0.85 ± 0.05 | 1.01 ± 0.15 | 1.07 ± 0.08 |
Elovl5 (n-6) | 0.12 ± 0.00 | 0.11 ± 0.00 | 0.11 ± 0.00 |
Elovl2-5 (n-6) | 0.23 ± 0.00 | 0.22 ± 0.00 | 0.22 ± 0.01 |
Elovl2-5 (n-3) | 2.76 ± 0.22 | 2.65 ± 0.15 | 2.43 ± 0.14 |
Elovl2 (n-3) | 0.41 ± 0.03 | 0.40 ± 0.02 | 0.42 ± 0.03 |
Peroxisomal β-oxidation | 43.85 ± 3.05 | 54.04 ± 2.12 a,* | 56.40 ± 1.92 a,** |
Damage Marker | Adults | Aged | Aged+MetR |
---|---|---|---|
GSA | 3615.40 ± 79.03 | 3700.19 ± 138.23 | 3623.83 ± 246.00 |
CEL | 270.70 ± 15.58 | 259.79 ± 29.33 | 233.04 ± 11.36 |
CML | 966.24 ± 40.79 | 1016.19 ± 63.22 | 949.69 ± 85.01 |
MDAL | 372.59 ± 30.48 | 345.74 ± 6.80 | 376.28 ± 21.86 |
2-SC | 28.43 ± 4.18 | 20.78 ± 2.28 | 35.55 ± 4.99 b,* |
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Jové, M.; Cabré, R.; Mota-Martorell, N.; Martin-Garí, M.; Obis, È.; Ramos, P.; Canales, I.; Galo-Licona, J.D.; Sol, J.; Nogueras, L.; et al. Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age. Int. J. Mol. Sci. 2021, 22, 12517. https://doi.org/10.3390/ijms222212517
Jové M, Cabré R, Mota-Martorell N, Martin-Garí M, Obis È, Ramos P, Canales I, Galo-Licona JD, Sol J, Nogueras L, et al. Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age. International Journal of Molecular Sciences. 2021; 22(22):12517. https://doi.org/10.3390/ijms222212517
Chicago/Turabian StyleJové, Mariona, Rosanna Cabré, Natàlia Mota-Martorell, Meritxell Martin-Garí, Èlia Obis, Paula Ramos, Iván Canales, José Daniel Galo-Licona, Joaquim Sol, Lara Nogueras, and et al. 2021. "Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age" International Journal of Molecular Sciences 22, no. 22: 12517. https://doi.org/10.3390/ijms222212517