An Interplay between Inflammation, Oxidative Stress and Cellular Aging in a Controlled Human Malaria Challenge Study
39 Pages Posted: 10 Apr 2020 Publication Status: Review Complete
More...Abstract
Infectious diseases can potentially affect cellular aging by adding miles to the biological clock. Previous studies have shown that malaria infection accelerates cellular aging. However, the driving forces and inter-connectivity of the mechanisms underlying infection-mediated cellular senescence, are yet to be understood. Here, using a Controlled Human Malaria Infection (CHMI) model, we explored the mechanistic interplay of key regulators of cellular aging and infection. We reveal that a single low-density Plasmodium falciparum infection accelerated cellular aging by elevating inflammatory cytokines, and reducing anti-oxidant genes expression, with all changes reversing to base-line values after treatment. Parasite density was positively correlated with inflammatory cytokines, CDKN2A levels and liver function abnormalities, while negatively correlated with anti-oxidant gene expression and telomere length. PCA and Factor analysis produced three significant factors explaining 78.6% of the total variance, with all factors being strongly affected by infection. Results from our study provide insights on potential mechanisms underlying infection-driven cellular senescence, and suggests parasite mediated costs potentially leading to long-term impairments in the human host.
Keywords: CHMI, Malaria, Oxidative stress, Inflammation, Telomeres, CDKN2A, Aging
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