Blood-based biomarkers in centenarians and non-centenarians: a matched, population-based retrospective cohort study using primary care records in Catalonia, Spain

The global increase in life expectancy has sparked growing interest in the factors that contribute to exceptional longevity. Between 1990 and 2015, the number of centenarians worldwide more than quadrupled. This study aimed to analyse the relationship between blood-based biomarkers and the likelihood of reaching 100 years of age in Catalonia (2015-2022), and to examine how biomarker variations during COVID-19 affected longevity. Using a retrospective cohort study based on primary care electronic health records from Catalonia, we compared centenarians with individuals aged 92 or older who died before reaching 100 years of age. We analysed anaemia, cholesterol, glycemia, kidney function, and liver function biomarkers. We employed multiple strategies to control for confounding including matching without replacement, adjusting for both observed confounders at both the individual and contextual level, and unobserved confounders, in particular spatial dependence. Our findings reveal that centenarians exhibit higher rates of chronic conditions, greater socioeconomic disadvantage, and increased neighbourhood inequality in urban areas. Biologically, longevity was linked to intermediate levels of ferritin and cholesterol, alongside lower glucose, creatinine, and uric acid levels. Glycaemic balance, indicated by HbA1c and fasting glucose, emerged as a key factor in survival to extreme old age. Additionally, biomarker improvements during the pandemic correlated with an increased likelihood of reaching centenarian age. These results emphasize the complex interplay between biological, behavioural, and contextual factors in determining longevity. While biomarkers provide valuable insights, they are insufficient indicators of healthy ageing. Future research should integrate multiple dimensions, among them, environmental, and social determinants for uncovering the mechanisms of longevity.