The Impact of Biological Age on Surgical Outcomes - PROJECT SUMMARY Surgery is very common and risky for older adults. Nearly 25% of aging patients lose independence after surgery, and 13% die within 1 year, 3x higher than expected mortality without surgery and 3x higher than younger patients getting surgery. This trend is highly concerning for public health since the fraction of US adults older than 65 years continues to grow and there is no standardized way to incorporate aging into risk stratification for surgery. Despite the fact that chronological age (time since birth) is a known risk factor for postoperative outcomes, it is an insufficient proxy for health in older adults. Restricting surgical care based upon chronological age alone is imprecise and potentially harmful since it can exclude people who may benefit from surgery. As an alternative, molecular estimates of age, termed “biological age”, provide a quantitative, modifiable, and biologically-based estimate of health in older adults and are not simply a reflection of underlying comorbidities. Biological age can even distinguish disease- and mortality-risk in people of the same chronological age and comorbidities. Despite extensive evidence for the clinical impact of biological age, there is a significant knowledge gap: we have no understanding of how biological age impacts surgical outcomes. The proposed research aims to: (1) determine the effect of preoperative biological age on 1-year postop mortality; and (2) evaluate preoperative biological age as a predictor of loss of independence after surgery. This study will be conducted using the UKBiobank, a large prospective cohort study (N=502,649) that uniquely integrates molecular, clinical, questionnaire, and mortality data, to investigate surgical risk related two independent metrics of biological age relevant to surgical recovery – immunologic age and metabolic age. This project will be the first to test the hypothesis that preoperative biological age is associated with various patient- centered surgical outcomes, even when correcting for well-known medical, surgical, and sociodemographic risk factors. The contribution of our project will be significant because it will give us a way to distinguish biological risk for surgery in aging adults who are currently clinically indistinguishable. This will help guide shared decision-making between patients and surgeons before surgery. The successful completion of this project opens the door to targeting biological age with pharmacologic and non-pharmacological interventions to improve postoperative outcomes.
