Serum markers of biological ageing provide long-term prediction of life expectancy - A longitudinal analysis in middle-aged and older German adults

Abstract

Background: lifestyle behaviours and chronic co-morbidities are leading risk factors for premature mortality and collectively predict wide variability in individual life expectancy (LE). We investigated whether a pre-selected panel of five serum markers of biological ageing could improve predicting the long-term mortality risk and LE in middle-aged and older women and men. Methods: we conducted a case-cohort study (n = 5,789 among which there were 2,571 deaths) within the European Prospective Investigation into Cancer-Heidelberg cohort, a population cohort of middle-aged and older individuals, followed over a median duration of 18 years. Gompertz models were used to compute multi-adjusted associations of growth differentiation factor-15, N-terminal pro-brain natriuretic peptide, glycated haemoglobin A1c, C-reactive protein and cystatin-C with mortality risk. Areas under estimated Gompertz survival curves were used to estimate the LE of individuals using a model with lifestyle-related risk factors only (smoking history, body mass index, waist circumference, alcohol, physical inactivity, diabetes and hypertension), or with lifestyle factors plus the ageing-related markers. Results: a model including only lifestyle-related factors predicted a LE difference of 16.8 [95% confidence interval: 15.9; 19.1] years in men and 9.87 [9.20; 13.1] years in women aged ≥60 years by comparing individuals in the highest versus the lowest quintiles of estimated mortality risk. Including the ageing-related biomarkers in the model increased these differences up to 22.7 [22.3; 26.9] years in men and 14.00 [12.9; 18.2] years in women. Conclusions: serum markers of ageing are potentially strong predictors for long-term mortality risk in a general population sample of older and middle-aged individuals and may help to identify individuals at higher risk of premature death, who could benefit from interventions to prevent further ageing-related health declines.