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Biomarkers of cellular aging during a controlled human malaria infection
Aurelie Miglar1,2,3, Isaie J Reuling4, Xi Zen Yap4
1Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Abstract:
Cellular aging is difficult to study in individuals with natural infection, given the diversity of symptom duration and clinical presentation, and the high interference of aging-related processes with host and environmental factors. To address this challenge, we took advantage of the controlled human malaria infection (CHMI) model. This approach allowed us to characterize the relationship among cellular aging markers prior, during and post malaria pathophysiology in humans, controlling for infection dose, individual heterogeneity, previous exposure and co-infections. We demonstrate that already low levels of Plasmodium falciparum impact cellular aging by inducing high levels of inflammation and redox-imbalance; and that cellular senescence reversed after treatment and parasite clearance. This study provides insights into the complex relationship of telomere length, cellular senescence, telomerase expression and aging-related processes during a single malaria infection.
Insights
Malaria infection, even at low levels, accelerates cellular aging by increasing inflammation and oxidative stress. This cellular aging effect reverses after malaria treatment and parasite clearance in humans.
Area of Science:
- Immunology
- Infectious Diseases
- Cellular Biology
Background:
- Studying cellular aging during natural malaria infection is challenging due to variable symptoms and confounding factors.
- The controlled human malaria infection (CHMI) model offers a standardized approach to investigate infection-related biological changes.
Purpose of the Study:
- To investigate the impact of Plasmodium falciparum infection on cellular aging markers.
- To characterize the dynamics of cellular aging before, during, and after malaria pathophysiology in a controlled setting.
Main Methods:
- Utilized the controlled human malaria infection (CHMI) model for standardized infection.
- Monitored cellular aging markers, inflammation, and redox balance.
- Assessed changes in telomere length, cellular senescence, and telomerase expression.
Main Results:
- Low-level Plasmodium falciparum infection significantly increased inflammation and redox imbalance, indicative of accelerated cellular aging.
- Cellular senescence markers were elevated during infection.
- These aging markers returned to baseline levels after antimalarial treatment and parasite clearance.
Conclusions:
- Plasmodium falciparum infection directly impacts cellular aging pathways.
- The CHMI model is effective for studying infection-induced aging.
- Cellular aging markers are reversible upon successful malaria treatment.
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