Age-Related Changes in Serum N-Glycome in Men and Women—Clusters Associated with Comorbidity
Abstract
:1. Introduction
2. Methods
2.1. Study Design and Setting
2.2. Ethical Issues
2.3. Assessment of Smoking
2.4. Assessment of Alcohol Drinking
2.5. Usual Physical Activity History
2.6. Definition of Metabolic Disorders
2.7. Definition of Comorbidities and Their Quantification
2.8. Routine Analytical Determinations
2.9. Determination of Inflammation Markers
2.10. Determination of Glycation Markers (Markers of Glycaemic Control)
2.11. Serum N-Glycan Analyses
2.12. Statistical Analyses
3. Results
3.1. N-Glycan Peaks (GPs) in Relation to Age and Sex
- Group 1: GPs that are less abundant in women at younger ages, but increase in abundance over the years at a faster rate in this sex, so that at advanced ages their abundance becomes either equal or even higher than that of men. These are GP1, GP2, GP3, GP5, GP32, GP40, GP41, GP44, GP45, and GP46.
- Group 2: GPs that are more abundant in women at younger ages, but their abundance becomes equal or even higher in men in advances ages because they increase faster in men over the years (GP7, GP10, GP15, GP16, and GP23), or they decrease faster in women over the years (GP14, GP22, and GP24).
- Group 3: GPs that are similarly abundant in both sexes at young ages, but their abundance increases more prominently in women than in men over the years (GP39 and GP43).
- Group 4: GPs that are more abundant in one sex, regardless of age. They are GP29, GP30, GP31, GP33, GP34, GP36, and GP42 (more abundant in women), and GP35 and GP38 (more abundant in men).
- Group 5: GPs whose abundance increases or decreases over the years of age, but without clear differences between men and women. They are GP6, GP11, GP26, GP28, and GP37 (they increase over the years) and GP8, GP9, GP13, and GP18 (they decrease over the years).
- Group 6: GPs whose profile does not fit into any of the previous groups (GP4, GP12, GP17, GP19, GP20, GP21, GP25, and GP27).
3.2. N-Glycan Groups (as Defined by Common Features) in Relation to Age and Sex
- Group 1: An increase in abundance with age in men and women is observed for simple N-glycans such as agalactosylated (G0), monoantennary (A1), non-sialylated (S0, although not statistically significant in this case), and oligomannose (OM) N-glycans. The abundance of N-glycans with peripheral (outer-arm, OF) fucosylation also increase significantly with age, although it stabilizes after 50 years of age in both sexes.
- Group 2: A decrease in abundance with age in men and women is observed for digalactosylated (G2), biantennary (A2, although it stabilizes in men from middle age onwards), monosialylated (S1, although more significantly in women) and core-fucosylated (CF) N-glycans.
- Group 3: A trend to increase in abundance with age is observed for with tetrasialylated (S4), tetragalactosylated (G4), and tetraantennary (A4) N-glycans in women, while in men the abundance remains stable at a higher level, which tends to equal that of women at advanced ages.
- Group 4: An increase in abundance with age in both sexes is observed for trigalactosylated (G3) and triantennary (A3, with a non-significant trend in this case) N-glycans, although always at a higher level of abundance in women.
- Group 5: A divergent change in abundance with age between men and women starting at middle age (possibly coinciding with menopause in women) is observed for trisialylated (S3, which decrease in men with a continuous increase in women), and biantennary (A2, that stabilize at that age in men, with a continuous decline in women) N-glycans.
- Group 6: A difference in the abundance between men and women up to middle age is observed for agalactosylated (G0) N-glycans (more abundant in men), and monosialylated (S1) N-glycans (more abundant in women) (Figure 2).
3.3. Clusters Defined by Principal Component Analysis (PCA) and k-Means Clustering
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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N-Glycan Trait (%) | Total Sample (n = 1516) | Cluster 1 (n = 431) | Cluster 2 (n = 1085) | p-Value |
---|---|---|---|---|
G0 | 3.19 (2.40, 4.53) | 5.75 (4.47, 7.92) | 2.76 (2.20, 3.41) | <0.001 |
G1 | 6.95 (6.05, 8.26) | 9.59 (8.44, 11.60) | 6.41 (5.72, 7.14) | <0.001 |
G2 | 67.98 (65.43, 69.98) | 64.98 (61.46, 68.21) | 68.57 (66.82, 70.45) | <0.001 |
G3 | 13.48 (11.54, 15.41) | 11.28 (9.83, 12.95) | 14.30 (12.52, 15.92) | <0.001 |
G4 | 6.22 (5.09, 7.58) | 5.22 (4.29, 6.23) | 6.66 (5.62, 7.89) | <0.001 |
A1 | 1.08 (0.95, 1.22) | 1.30 (1.16, 1.49) | 1.01 (0.91, 1.12) | <0.001 |
A2 | 77.76 (75.70, 79.82) | 80.05 (78.34, 81.48) | 76.92 (75.07, 78.63) | <0.001 |
A3 | 13.48 (11.54, 15.41) | 11.28 (9.83, 12.95) | 14.30 (12.52, 15.92) | <0.001 |
A4 | 6.22 (5.09, 7.58) | 5.22 (4.29, 6.23) | 6.66 (5.62, 7.89) | <0.001 |
S0 | 11.83 (9.82, 14.69) | 17.92 (15.23, 23.93) | 10.66 (9.26, 12.08) | <0.001 |
S1 | 21.15 (19.48, 22.85) | 21.37 (19.59, 23.27) | 21.08 (19.45, 22.63) | 0.085 |
S2 | 49.50 (47.16, 51.29) | 45.02 (42.05, 47.60) | 50.39 (49.00, 52.03) | <0.001 |
S3 | 14.87 (13.06, 16.59) | 12.57 (11.17, 13.96) | 15.68 (14.35, 17.15) | <0.001 |
S4 | 1.82 (1.50, 2.13) | 1.48 (1.26, 1.76) | 1.93 (1.68, 2.23) | <0.001 |
CF | 30.44 (27.23, 33.93) | 35.68 (32.65, 39.53) | 28.76 (26.09, 31.45) | <0.001 |
OF | 2.67 (2.28, 3.12) | 2.30 (1.96, 2.61) | 2.83 (2.45, 3.25) | <0.001 |
OM | 1.10 (0.91, 1.40) | 1.76 (1.40, 2.65) | 0.99 (0.86, 1.15) | <0.001 |
Cluster 1 (n = 431) | Cluster 2 (n = 1085) | p-Value | |
---|---|---|---|
Age, years | 56 (40, 70) | 51 (38.00, 65) | 0.002 |
Women, n (%) | 232 (53.8) | 606 (55.8) | 0.608 |
Men, n (%) | 199 (46.2) | 479 (44.2) | |
Smoking status | |||
Never smokers, n (%) | 237 (55.0) | 588 (54.2) | 0.031 |
Ex-smokers, n (%) | 128 (29.7) | 267 (24.6) | |
Smokers, n (%) | 66 (15.3) | 230 (21.2) | |
Physical activity | |||
Low, n (%) | 165 (38.3) | 431 (39.7) | 0.891 |
Medium, n (%) | 161 (37.3) | 391 (36.0) | |
High, n (%) | 105 (24.4) | 263 (24.2) | |
Alcohol consumption (g/day) | |||
0–9, n (%) | 159 (36.9) | 387 (35.7) | 0.468 |
10–139, n (%) | 162 (37.6) | 436 (40.2) | |
140–279, n (%) | 78 (18.1) | 163 (15.0) | |
≥280, n (%) | 32 (7.4) | 99 (9.1) | |
Body mass index, kg/m2 | 27.7 (24.5, 31.5) | 27.7 (24.6, 31.3) | 0.726 |
Diabetes mellitus, n (%) | 61 (14.2) | 126 (11.6) | 0.358 |
Metabolic syndrome, n (%) | 95 (22.0) | 219 (20.2) | 0.608 |
Serum glucose, mg/dL | 91 (83, 102) | 88 (81, 98) | 0.006 |
Blood glycated hemoglobin (HbA1c), % | 5.4 (5.2, 5.8) | 5.4 (5.2, 5.7) | 0.752 |
Serum glycated albumin, % | 14.1 (13.0, 15.5) | 13.6 (12.4, 14.8) | <0.001 |
Serum fructosamine, μmol/L | 262 (237, 292) | 251 (220, 279) | <0.001 |
Serum HDL-cholesterol, mg/dL | 59 (49, 71) | 57 (46, 68) | 0.006 |
Serum LDL-cholesterol, mg/dL | 114 (93, 137) | 113 (94, 134) | 0.905 |
Erythrocyte sedimentation rate (ESR), mm/h | 9 (5, 17) | 9 (5, 16) | 0.326 |
Serum C-reactive protein, mg/dL | 0.13 (0.04, 0.33) | 0.14 (0.05, 0.41) | 0.358 |
Serum TNF-alpha, pg/mL | 7.6 (6.4, 9.6) | 7.4 (6.0, 8.8) | 0.001 |
Serum interleukin-8 (IL-8), pg/mL | 7.0 (5.0, 10.0) | 7.0 (5.0, 11.0) | 0.608 |
Serum interleukin-6 (IL-6), pg/mL | 2.1 (2.0, 3.2) | 2.2 (2.0, 3.6) | 0.358 |
Serum soluble interleukin-2 receptor, U/mL | 414 (321, 527) | 411 (313, 530) | 0.608 |
Serum aspartate aminotransferase (AST), IU/L | 23 (20, 28) | 22 (19, 27) | 0.002 |
Gamma-glutamyl transferase (GGT), IU/L | 21 (14, 34) | 19 (13, 33) | 0.069 |
Serum triiodothyronine (T3), pg/mL | 3.30 (3.05, 3.56) | 3.39 (3.15, 3.67) | 0.001 |
Glomerular filtration rate, mL/min/1.7 m2 | 96.8 (84.5, 111.8) | 101.9 (88.3, 117.2) | 0.001 |
Comorbidity index | |||
0 points | 296 (68.7) | 789 (72.7) | 0.015 |
1 point | 84 (19.5) | 222 (20.5) | |
≥2 points | 51 (11.8) | 74 (6.8) |
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Lado-Baleato, Ó.; Torre, J.; O’Flaherty, R.; Alonso-Sampedro, M.; Carballo, I.; Fernández-Merino, C.; Vidal, C.; Gude, F.; Saldova, R.; González-Quintela, A. Age-Related Changes in Serum N-Glycome in Men and Women—Clusters Associated with Comorbidity. Biomolecules 2024, 14, 17. https://doi.org/10.3390/biom14010017
Lado-Baleato Ó, Torre J, O’Flaherty R, Alonso-Sampedro M, Carballo I, Fernández-Merino C, Vidal C, Gude F, Saldova R, González-Quintela A. Age-Related Changes in Serum N-Glycome in Men and Women—Clusters Associated with Comorbidity. Biomolecules. 2024; 14(1):17. https://doi.org/10.3390/biom14010017
Chicago/Turabian StyleLado-Baleato, Óscar, Jorge Torre, Róisín O’Flaherty, Manuela Alonso-Sampedro, Iago Carballo, Carmen Fernández-Merino, Carmen Vidal, Francisco Gude, Radka Saldova, and Arturo González-Quintela. 2024. "Age-Related Changes in Serum N-Glycome in Men and Women—Clusters Associated with Comorbidity" Biomolecules 14, no. 1: 17. https://doi.org/10.3390/biom14010017
APA StyleLado-Baleato, Ó., Torre, J., O’Flaherty, R., Alonso-Sampedro, M., Carballo, I., Fernández-Merino, C., Vidal, C., Gude, F., Saldova, R., & González-Quintela, A. (2024). Age-Related Changes in Serum N-Glycome in Men and Women—Clusters Associated with Comorbidity. Biomolecules, 14(1), 17. https://doi.org/10.3390/biom14010017