Epigenetic age biomarkers and risk assessment in adult spinal deformity: a novel association of biological age with frailty and disability
Bibliographic record
Abstract
OBJECTIVE: Surgery for spinal deformity has the potential to improve pain, disability, function, self-image, and mental health. These surgical procedures carry significant risk and require careful selection, optimization, and risk assessment. Epigenetic clocks are age estimation tools derived by measuring the methylation patterns of specific DNA regions. The study of biological age in the adult deformity population has the potential to shed insight onto the molecular basis of frailty and to improve current risk assessment tools. METHODS: Adult patients who underwent deformity surgery were prospectively enrolled. Preoperative whole blood samples were used to assess epigenetic age and telomere length. DNA methylation patterns were quantified and processed to extract 4 principal component (PC)-based epigenetic age clocks (PC Horvath, PC Hannum, PC PhenoAge, and PC GrimAge) and the instantaneous pace of aging (DunedinPACE). Telomere length was assessed using both quantitative polymerase chain reaction (telomere to single gene [T/S] ratio) and a methylation-based telomere estimator (PC DNAmTL). Patient demographic and surgical data included age, BMI, American Society of Anesthesiologists Physical Status Classification System class, and scores on the Charlson Comorbidity Index, adult spinal deformity frailty index (ASD-FI), Edmonton Frail Scale (EFS), Oswestry Disability Index, and Scoliosis Research Society-22r questionnaire (SRS-22r). Medical or surgical complications within 90 days of surgery were collected. Spearman correlations and beta coefficients (β) from linear regression, adjusted for BMI and sex, were calculated. RESULTS: Eighty-three patients were enrolled with a mean age of 65 years, and 45 were women (54%). All patients underwent posterior fusion with a mean of 11 levels fused and 33 (40%) 3-column osteotomies were performed. Among the epigenetic clocks adjusted for BMI and sex, DunedinPACE showed a significant association with ASD-FI (β = 0.041, p = 0.002), EFS (β = 0.696, p = 0.026), and SRS-22r (β = 0.174, p = 0.013) scores. PC PhenoAge showed associations with ASD-FI (β = 0.029, p = 0.028) and SRS-22r (β = 0.159, p = 0.018) scores. PC GrimAge showed associations with ASD-FI (β = 0.029, p = 0.037) and SRS-22r (β = 0.161, p = 0.025) scores. Patients with postoperative complications were noted to have shorter telomere length (T/S 0.790 vs 0.858, p = 0.049), even when the analysis controlled for BMI and sex (OR = 1.71, 95% CI 1.07-2.87, p = 0.031). CONCLUSIONS: Epigenetic clocks showed significant associations with markers of frailty and disability, while patients with postoperative complications had shorter telomere length. These data suggest a potential role for aging biomarkers as components of surgical risk assessment. Integrating biological age into current risk calculators may improve their accuracy and provide valuable information for patients, surgeons, and payers.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".