Associations between infection and organ age gaps: results from the UK Biobank

Background
Infection may have lasting influences in multiple organ systems, but its associations with organ-specific biological age remain unclear. We aimed to examine associations between infection burden (IB) and organ age gaps.
Methods
Among 42,395 UK Biobank participants, qualifying infection diagnoses were identified from first occurrences data. The IB score was defined as the number of distinct infection diagnoses first recorded before baseline. Participants were classified according to whether at least one qualifying infection diagnosis had hospital inpatient data as its earliest-record source, and infections were grouped into eight predefined categories. Biological ages of 18 organs were calculated from plasma proteomics-based organ signatures, with higher organ age gap (OAG) indicating accelerated aging process. Linear regression and restricted cubic spline models were used to examine associations between infections and OAG.
Results
Higher IB score was positively associated with OAG of 12 in 18 organs. IB-OAG associations were statistically significant for hospital-treated infections, but not for non-hospital-treated only infections. Among eight infected subcategories, sepsis showed the strongest and most widespread associations with OAG. Associations between IB score and OAG of heart, kidney, and pancreas were significantly nonlinear. In addition, associations were generally stronger for infection diagnoses first recorded in more recent time windows and weaker for diagnoses first recorded further in the past.
Conclusions
IB was associated with accelerated multi-organ aging, particularly for hospital-treated infections and sepsis. Our findings highlighted the critical roles of infection in organ aging, which provided clues to make tailored strategies for the prevention of aging related disorders.