Infectious diseases could potentially reduce lifespan by contributing to accelerated aging process and adding miles to the biological clock. Recently, we have shown that chronic asymptomatic malaria infection reduced ~ 50% percent lifespan, mediated through faster telomere shortening in birds. The purpose of this proposal is to investigate the extent to which infectious diseases drive cellular aging and if there is a long-term hidden cost of chronic asymptomatic infections on cellular aging in humans. We will take experimental, epidemiological and cellular approaches to approach the objective. First, we will establish the causal effect of malaria on cellular aging in a controlled human malaria challenge (CHMI) study performed at Nijmegen, the Netherlands. Secondly, we will investigate the effect of repeated or persistent asymptomatic malaria infections on cellular aging in well characterized longitudinal studies in Tanzania and Kenya. Finally, we will perform in-depth analysis of cellular aging in different human pathologies (malaria, influenza and bacterial infection) by sorting different subcell populations to investigate the effect of infections in cellular aging in different subcell populations. This project has the potential to provide translational impact through mechanistic insight into infectious diseases pathophysiology and its effects on chromosome stability and aging. Overall, this project will push the aging and infectious diseases fields forward significantly.