Table 2.
The associations between metabolomic age deviations (MAD) and age-related diseases, as determined by Cox proportional hazards models
| Outcome | Model* | C-Index | HR | 95% CI | p-value** |
|---|---|---|---|---|---|
| Mortality | MAD | 0.841 | 1.08 | [1.06–1.10] | 8.1 × 10−11 |
| N = 1285, N events = 9 | Null | 0.809 | -*** | - | - |
| MAD Extended | 0.863 | 1.09 | [1.06–1.13] | 2.2 × 10−7 | |
| Null Extended | 0.851 | - | - | - | |
| Diabetes | MAD | 0.654 | 1.05 | [1.04–1.07] | 1.8 × 10−13 |
| N = 942, N events = 236 | Null | 0.594 | - | - | - |
| MAD Extended | 0.676 | 1.04 | [1.03–1.06] | 1.8 × 10−6 | |
| Null Extended | 0.656 | - | - | - | |
| COPD | MAD | 0.692 | 1.05 | [1.03–1.07] | 6.2 × 10−7 |
| N = 1063, N events = 108 | Null | 0.655 | - | - | - |
| MAD Extended | 0.757 | 1.05 | [1.02–1.06] | 0.001 | |
| Null Extended | 0.746 | - | - | - | |
| Stroke | MAD | 0.712 | 1.07 | [1.04–1.11] | 4.2 × 10−4 |
| N = 1108, N events = 30 | Null | 0.649 | - | - | - |
| MAD Extended | 0.723 | 1.07 | [1.03–1.11] | 0.02 | |
| Null Extended | 0.673 | - | - | - | |
| Kidney disease | MAD | 0.641 | 1.05 | [1.02–1.08] | 0.04 |
| N = 1096, N events = 49 | Null | 0.594 | - | - | - |
| MAD Extended | 0.652 | 1.05 | [1.01–1.08] | 0.07 | |
| Null Extended | 0.618 | - | - | - | |
| Cancer | MAD | 0.642 | 1.00 | [0.98–1.02] | 1 |
| N = 962, N events = 194 | Null | 0.642 | - | - | - |
| MAD Extended | 0.656 | 1.00 | [0.98–1.02] | 1 | |
| Null Extended | 0.655 | - | - | - | |
| Dementia or Alzheimer’s | MAD | 0.908 | 0.92 | [0.80–1.06] | 1 |
| disease | Null | 0.896 | - | - | - |
| N = 1126, N events = 5 | MAD_Extended | 0.955 | 0.94 | [0.79–1.11] | 1 |
| Null_Extended | 0.954 | - | - | - |
* Each model was adjusted for sex and age. Hazard ratios (HRs) of MAD corresponding to each model are shown alongside their 95% confidence intervals (CIs). MAD are the residuals of the Sweet Spot Clock, calibrated into units of age, and then regressed onto age. The null model had age and sex as predictors. Extended models were additionally adjusted for body mass index, alcohol consumption, smoking status, physical activity level, and level of education.
** The p-values were obtained from two-sided Wald’s tests and Bonferroni-adjusted (n = 14).
*** HRs shown in this table correspond to the metabolomic biomarker only, as they quantify its added predictive value beyond the covariates. The Null and Extended Null models do not include the biomarker and therefore do not provide an HR. HRs for all covariates in all models are reported in Supplementary Data 6.