Table 1.
Current inflamm-aging-related biomarkers and pathways.
| Biomarker | Mechanism | Ref. |
|---|---|---|
| Immune cell markers | ||
| NK↑CD14+CD56dim/↓CD14+CD56bright | Accumulation of immature NK cells | [28,29] |
| NK↓NKP30, NKP46, DNAM-1 and ↑KIR, NKG2C | Decrease in activating receptors and increase in inhibitory receptors on NK cells | [29,30,31,32] |
| Monocyte↑CD14+(low)CD16+ and CD14++(high)CD16+/↓CD14+(low)CD16− | Increase in immature monocytes | [33] |
| Macrophage↓CD62L and TLR1/4/↑CD11b and TLR5 | Decrease in activating receptors and increase in inhibitory receptors on macrophages | [34] |
| Macrophage M1→M2 | Macrophage phenotype switch to proinflammatory | [35,36] |
| CD8+ naïve T cells | Decline in naïve T cells to reduce thymus T cell output | [37,38] |
| T cell↓CD27, CD28/↑KLRG-1, PD-1, CTLA-4, Tim-3, Tigit, CD57 | Downregulation of costimulatory molecules and upregulation of inhibitory molecules on T cells | [39,40] |
| B cell↓CD19+ | Downregulation in CD19+ B cells to impair B cell function | [41] |
| Cytokines | ||
| ↓IFN-γ, granzyme B, perforin | Reduction in dendritic cell and cytotoxic T cell activity | [42,43,44,45,46] |
| ↑IL-10, TGF-β, VEGF, indoleamine-2,3-dioxygenase | Increase in immunosuppressive cytokines | [8,47] |
| ↑IL-6, IL-1, TNF-α, CRP | Increase in proinflammatory cytokines | [8,48,49] |
| ↓IL-7 | Reduced activation of T cells | [11] |
| miRNAs | ||
| MiR-9, miRNA-17, miR-10a, miR-19a/b, miR-20, miRNA-21, miR-29a, miR-125a/b, miR-126, and miR-146a, miR-155, miR-181a/b, miR-187, miR-195, miR-199, miR-223, miR-517a/c, Let-7, Let-7i | Modulate signaling pathways implicated in inflamm-aging including NF-κB, mTOR, sirtuins, and TGF-β | [50,51] |
| Cell signaling pathways | ||
| NF-κB | A nuclear transcription factor that serves as the primary molecular switch for inflammatory pathways | [52] |
| mTOR | Activates NF-κB -mediated regulation of inflamm-aging | [53] |
| RIG-1 | Interacts with increased IL-6 and IL-8 levels in senescent cells and upregulates IL-6 expression | [54] |
| Notch | Induces senescence of endothelial cells | [55] |
| Sirtuin | Interacts with NF-κB to suppress its proinflammatory activity | [56] |
| TGF-β | Anti-inflammatory cytokine that deactivates macrophages to maintain immune homeostasis | [56] |
| Ras | Upregulates expression of proinflammatory cytokines | [57] |
Abbreviations: ↑, upregulation; ↓, downregulation; NK, natural killer cells; CD, cluster of differentiation; DNAM-1, DNAX accessory molecule; KIR, killer cell Ig-like receptors; TLR, toll-like receptor; KLRG1, killer cell lectin-like receptor G1; PD-1, programmed cell death protein 1; CTLA-4, cytotoxic T-lymphocyte associated protein 4; Tim-3, T cell immunoglobulin, and mucin-domain containing-3; Tigit, T-cell immunoglobulin, and ITIM domain; IFN, interferon; IL, interleukin; TGF, transforming growth factor; VEGF, vascular endothelial growth factor; TNF, tumor necrosis factor; CRP, c-reactive protein; MiRNA, microRNA; NF-κB, nuclear factor kappa B; mTOR, mammalian target of rapamycin; RIG-1, retinoic acid-inducible gene I.