Aging-related defects in macrophage function are driven by MYC and USF1 transcriptional programs.
Cell Rep
; 43(4): 114073, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38578825
ABSTRACT
Macrophages are central innate immune cells whose function declines with age. The molecular mechanisms underlying age-related changes remain poorly understood, particularly in human macrophages. We report a substantial reduction in phagocytosis, migration, and chemotaxis in human monocyte-derived macrophages (MDMs) from older (>50 years old) compared with younger (18-30 years old) donors, alongside downregulation of transcription factors MYC and USF1. In MDMs from young donors, knockdown of MYC or USF1 decreases phagocytosis and chemotaxis and alters the expression of associated genes, alongside adhesion and extracellular matrix remodeling. A concordant dysregulation of MYC and USF1 target genes is also seen in MDMs from older donors. Furthermore, older age and loss of either MYC or USF1 in MDMs leads to an increased cell size, altered morphology, and reduced actin content. Together, these results define MYC and USF1 as key drivers of MDM age-related functional decline and identify downstream targets to improve macrophage function in aging.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fagocitose
/
Envelhecimento
/
Proteínas Proto-Oncogênicas c-myc
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Fatores Estimuladores Upstream
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Macrófagos
Limite:
Adolescent
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Adult
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Aged
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Humans
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Middle aged
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2024
Tipo de documento:
Article