Abstract
Long-lived individuals are central in studies of healthy longevity. However, few pro-longevity factors have been identified, presumably because of "phenocopies", i.e. individuals that live long by chance. Familial longevity cases may include less phenocopies than sporadic cases and provide better insights into longevity mechanisms. Here we examined whether long-lived female siblings have a better ability to avoid diseases at ages 65+ (proxy for "robustness") and/or survive to extreme ages (proxy for "resilience") compared to sporadic long-livers. A total of 1,156 long-lived female siblings were selected from three nationwide Danish studies and age-matched with sporadic long-lived female controls. Outcomes included cumulative incidence of common health disorders from age 65 and overall survival. Long-lived female siblings had lower risks of some but not all health conditions, most significantly, depression (OR=0.74; 95%CI=0.62-0.88), and less significantly hypertensive (OR=0.84; 95%CI=0.71-0.99) and cerebrovascular (OR=0.73; 95%CI=0.55-0.96) diseases. They also had consistently better survival to extreme ages (HR=0.71; 95%CI= 0.63-0.81) compared to sporadic long-livers. After adjustment for the diseases, the association with mortality changed only marginally suggesting central role of better physiological resilience in familial longevity. Due to their consistently better resilience, familial longevity cases could be more informative than sporadic cases for studying mechanisms of healthy longevity.