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Macrophages, a critical subset of innate immune cells, play a pivotal role in cytokine production during disease progression, tissue injury, and pathogen invasion. Their intricate involvement in the manifestation of chronic low-grade inflammation associated with the aging process is widely acknowledged. Notably, in aged tissues, macrophages exhibit an altered phenotype characterized by an augmented synthesis of pro-inflammatory cytokines and chemokines, a profile intimately associated with a phenomenon known as inflammaging. Macrophages possess the capacity to undergo cellular senescence, a state of permanent growth arrest, in response to diverse stressors, including aging. Senescent macrophages secrete an array of pro-inflammatory molecules, growth factors, and matrix metalloproteinases, collectively referred to as the Senescence-Associated Secretory Phenotype (SASP). The SASP exacerbates the state of chronic inflammation observed in aging tissues. Thus, disruptions in macrophage function and signaling pathways due to aging result in escalated production of inflammatory mediators, perpetuating inflammaging. Recent research has uncovered novel mechanisms centred around innate immune signaling and mitochondrial dysfunction in macrophages, highlighting their crucial role in the development of inflammaging and associated pathological conditions. This review delves into the latest scientific findings on these emerging mechanisms in macrophage senescence related to aging and explores the prospects of targeting macrophages to address age- associated conditions effectively.

Neurodegenerative diseases (NDs) demonstrate a complex interaction with the immune system, challenging the traditional view of the brain as an "immune-privileged" organ. Microglia were once considered the sole guardians of the brain's immune response. However, recent research has revealed the critical role of peripheral immune cells located in key brain regions like the meninges, choroid plexus, and perivascular spaces. These previously overlooked cells are now recognized as contributors to the development and progression of NDs. This newfound understanding opens doors for pioneering therapeutic strategies. By targeting these peripheral immune cells, we may be able to modulate the brain's immune environment, offering an alternative approach to treat NDs and circumvent the challenges posed by the blood-brain barrier. This comprehensive review will scrutinize the latest findings on the complex interactions between these peripheral immune cells and NDs. It will also critically assess the prospects of targeting these cells as a ground-breaking therapeutic avenue for these debilitating disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Tuberculosis (TB) is the leading cause of global morbidity and mortality resulting from infectious disease, with over 10.6 million new cases and 1.4 million deaths in 2021. This global emergency is exacerbated by the emergence of multidrug-resistant MDR-TB and extensively drug-resistant XDR-TB; therefore, new drugs and new drug targets are urgently required. From a whole cell phenotypic screen, a series of azetidines derivatives termed BGAz, which elicit potent bactericidal activity with MIC 99 values <10 μM against drug-sensitive Mycobacterium tuberculosis and MDR-TB, were identified. These compounds demonstrate no detectable drug resistance. The mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with cell envelope biogenesis, specifically late-stage mycolic acid biosynthesis. Transcriptomic analysis demonstrates that the BGAz compounds tested display a mode of action distinct from the existing mycobacterial cell wall inhibitors. In addition, the compounds tested exhibit toxicological and PK/PD profiles that pave the way for their development as antitubercular chemotherapies.