Stopping malaria at the front door!

Malaria has accompanied humans for thousands of years, adapting alongside us and remaining one of the world’s most persistent infectious diseases. While the symptoms of malaria arise from parasite replication in the blood, infection begins much earlier—silently—when Plasmodium first passes through the liver. This brief and hidden stage is a critical bottleneck in the parasite’s life cycle, and blocking entry into or exit from the liver can prevent both disease and transmission. Despite its importance, natural infection rarely generates strong or lasting immunity against the liver stage of Plasmodium falciparum, even in highly endemic regions. Understanding why this immune protection fails—and how it can be enhanced—has become a central focus in malaria research. In their Trends in Parasitology Review, the Molecular Parasitology Group (Kai Matuschewski) reviewed recent advances in uncovering the immune mechanisms that target liver-stage parasites and discussed how these insights are guiding the development of current and next-generation malaria interventions.

Abstract

Neuroimaging and machine learning are advancing research into the mechanisms of biological aging. In this field, ‘brain age gap’ has emerged as a promising magnetic resonance imaging-based biomarker that quantifies the deviation between an individual’s biological and chronological age of the brain. Here we conducted an in-depth genomic analysis of the brain age gap and its relationships with over 1,000 health traits. Genome-wide analyses in up to 56,348 individuals unveiled a heritability of 23–29% attributable to common genetic variants and highlighted 59 associated loci (39 novel). The leading locus encompasses MAPT, encoding the tau protein central to Alzheimer’s disease. Genetic correlations revealed relationships with mental health, physical health, lifestyle and socioeconomic traits, including depressed mood, diabetes, alcohol intake and income. Mendelian randomization indicated a causal role of high blood pressure and type 2 diabetes in accelerated brain aging. Our study highlights key genes and pathways related to neurogenesis, immune-system-related processes and small GTPase binding, laying the foundation for further mechanistic exploration.