Mitochondrial dysfunction at the cornerstone of inflammatory exacerbation in aged macrophages.

Autor:	Maurmann RM; College of Health Sciences, University of Memphis, Memphis, Tennessee, 38152, USA., Schmitt BL; College of Health Sciences, University of Memphis, Memphis, Tennessee, 38152, USA., Mosalmanzadeh N; College of Health Sciences, University of Memphis, Memphis, Tennessee, 38152, USA., Pence BD; College of Health Sciences, University of Memphis, Memphis, Tennessee, 38152, USA.
Jazyk:	angličtina
Zdroj:	Exploration of immunology [Explor Immunol] 2023; Vol. 3 (5), pp. 442-452. Date of Electronic Publication: 2023 Oct 11.
DOI:	10.37349/ei.2023.00112
Abstrakt:	Immunosenescence encompasses multiple age-related adaptations that result in increased susceptibility to infections, chronic inflammatory disorders, and higher mortality risk. Macrophages are key innate cells implicated in inflammatory responses and tissue homeostasis, functions progressively compromised by aging. This process coincides with declining mitochondrial physiology, whose integrity is required to sustain and orchestrate immune responses. Indeed, multiple insults observed in aged macrophages have been implied as drivers of mitochondrial dysfunction, but how this translates into impaired immune function remains sparsely explored. This review provides a perspective on recent studies elucidating the underlying mechanisms linking dysregulated mitochondria homeostasis to immune function in aged macrophages. Genomic stress alongside defective mitochondrial turnover accounted for the progressive accumulation of damaged mitochondria in aged macrophages, thus resulting in a higher susceptibility to excessive mitochondrial DNA (mtDNA) leakage and reactive oxygen species (ROS) production. Increased levels of these mitochondrial products following infection were demonstrated to contribute to exacerbated inflammatory responses mediated by overstimulation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and cyclic GMP-ATP synthase (cGAS)-stimulator of interferon genes (STING) pathways. While these mechanisms are not fully elucidated, the present evidence provides a promising area to be explored and a renewed perspective of potential therapeutic targets for immunological dysfunction. Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest.
Databáze:	MEDLINE
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