Surgery-associated accelerated biological aging: Evidence from a cross-sectional study

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BACKGROUND: Surgery/anesthesia is major physiological stressors related to biological aging, while physical activity (PA) is known to have anti-aging effects. However, the relationship between PA and surgery-associated biological aging remains unclear. Therefore, we aimed to investigate the association between surgical history and biological aging and to examine whether PA modifies this relationship. METHODS: This cross-sectional study analyzed data from the UK Biobank, including 126,668 participants aged ≥60 years with complete surgical histories, PhenoAge biomarker data, and relevant covariates. Three analyses assessed associations between biological aging and number of major surgeries, shortest interval between adjacent surgeries, and time since most recent surgery. PA was assessed using questionnaire-derived MET-min/week, and PA levels were categorized as high (≥600) or low (<600 MET-min/week). Biological aging was measured using PhenoAge acceleration (PhenoAgeAccel), calculated from chronological age and nine clinical biomarkers (higher values indicate accelerated aging). Multivariable linear regression models adjusted for demographic characteristics, lifestyle factors, and comorbidities. RESULTS: Higher cumulative surgical exposure was significantly associated with PhenoAgeAccel. Compared to those with no surgeries, participants with ≥4 surgeries had a 0.14 to 0.39-year PhenoAgeAccel. Shorter surgical intervals (≤1 year) were associated with a 0.11-year PhenoAgeAccel compared to intervals >5 years. More recent surgery (≤1 year) was associated with a 0.35-year PhenoAgeAccel. High PA attenuated these associations. In high-PA individuals, statistically significant aging was observed only with ≥5 surgeries (vs ≥4 in low-PA) and within one year of recent surgery. No significant acceleration was observed in high-PA individuals with short surgical intervals. CONCLUSION: Number of surgeries, short surgical intervals, and recent surgery are associated with accelerated biological aging, which indicates that optimizing surgical timing may represent a potential strategy to mitigate the biological burden associated with repeated surgical exposure. Furthermore, the level of PA is negatively correlated with surgery-related aging.

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