Interleukin-6-Mediated Inflammation on Telomere Length Dynamics in Malaria Infection

Abstract

—Malaria, an infectious disease caused by Plasmodium species, remains a significant global health concern, contributing to millions of deaths annually, particularly in endemic regions. In 2023, approximately 263 million malaria cases were reported, according to the World Malaria Report. Malaria infection triggers an inflammatory response critical to its pathogenesis, with cytokines as potential biomarkers and therapeutic targets. Among these, interleukin-6 (IL-6) plays a crucial role in disease progression, immune regulation, and severity. Emerging evidence suggests that chronic inflammation induced by malaria infection may accelerate telomere attrition. Telomere length, a key biomarker of cellular aging, naturally declines with age; however, malaria-associated inflammation appears to expedite this process. Telomere shortening can be counteracted by Telomerase, an enzyme whose activity is tightly regulated by human Telomerase reverse transcriptase (hTERT). Telomerase and hTERT contribute to genomic stability and cellular longevity, with hTERT expression modulated by IL-6 through activation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway. Despite this understanding, the relationship between telomerase activity, telomere length, IL-6 levels, hTERT expression, and malaria infection remains poorly understood. This review synthesizes current findings on IL-6-mediated inflammation and its potential impact on telomere length, telomerase activity, and hTERT expression. We examine studies exploring how persistent inflammation in malaria may drive cellular senescence, telomere dysfunction, and disease severity. Gaining knowledge of how IL-6 regulates Telomerase may help identify new biomarkers, therapeutic targets, and immune based interventions for malaria-induced immune dysregulation. Future research should focus on elucidating the precise molecular mechanisms linking inflammation to telomere dynamics and exploring strategies to mitigate immune cell senescence in malaria patients.