Growth differentiation factor‐15 is associated with age‐related monocyte dysfunction

Abstract

Objective Age‐associated decreases in immune functions are precipitated by a variety of mechanisms and affect nearly every immune cell subset. In myeloid cells, aging reduces numbers of phagocytes and impairs their functional abilities, including antigen presentation, phagocytosis, and bacterial clearance. Recently, we described an aging effect on several functions in monocytes, including impaired mitochondrial function and reduced inflammatory cytokine gene expression during stimulation with lipopolysaccharide. We hypothesized that circulating factors altered by the aging process underly these changes. Growth differentiation factor‐15 (GDF‐15) is a distant member of the transforming growth factor‐β superfamily that has known anti‐inflammatory effects in macrophages and has been shown to be highly differentially expressed during aging. Methods We used biobanked plasma samples to assay circulating GDF‐15 levels in subjects from our previous studies and examined correlations between GDF‐15 and monocyte function. Results Monocyte interleukin‐6 production due to lipopolysaccharide stimulation was negatively correlated to plasma GDF‐15. Additionally, GDF‐15 was positively correlated to circulating CD16 + monocyte proportions and negatively correlated to monocyte mitochondrial respiratory capacity. Conclusions These results suggest that GDF‐15 is a potential circulating factor affecting a variety of monocyte functions and promoting monocyte immunosenescence and thus may be an attractive candidate for therapeutic intervention to ameliorate this.

Typhoid toxin hijacks Wnt5a to potentiate TGFβ-mediated senescence and Salmonella infections

“…The TGFβ family member GDF15 was immediately striking (Fig S3F), which was also identified in the TxWT-induced secretome (Fig 1H). GDF15 is differentially expressed during ageing, negatively regulates IL6 expression, and was identified as a SASP component promoting colon cancer (37)(38)(39).…”

Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes

“…The correlation of bright C 12 FDG ++ cells with extracellular biomarkers of age also provides strong supportive evidence that this assay may be a clinically relevant method to detect cells with functional senescence. One biomarker of particular interest was GDF‐15, a stress and inflammation responsive member of the TGF‐β superfamily that has been found to be a putative biomarker for aging (Conte et al., 2020 ; Liu et al., 2021 ; Pence et al., 2021 ). In our subjects, we found GDF‐15 to be strongly correlated with both chronological age and with percent C 12 FDG ++ PBMCs.…”

GDF15 as a potential biomarker to distinguish fibrotic from non-fibrotic hypersensitivity pneumonitis

“…It is highly secreted by fibroblasts and epithelial cells as part of the secretory SASP 18 . It has been also implicated as a potential causal link with age-related decline in immune function 19 .…”