Cellular Senescence and Inflammaging in the Skin Microenvironment

Abstract

Cellular senescence and aging result in a reduced ability to manage persistent types of inflammation. Thus, the chronic low-level inflammation associated with aging phenotype is called "inflammaging". Inflammaging is not only related with age-associated chronic systemic diseases such as cardiovascular disease and diabetes, but also skin aging. As the largest organ of the body, skin is continuously exposed to external stressors such as UV radiation, air particulate matter, and human microbiome. In this review article, we present mechanisms for accumulation of senescence cells in different compartments of the skin based on cell types, and their association with skin resident immune cells to describe changes in cutaneous immunity during the aging process.

Keywords: fibroblasts; immune cells; inflammaging; keratinocytes; melanocytes; senescence; skin.

Figure 1

The schematic view of cellular cross-talk between skin microenvironment and inflammaging. An illustrative overview of the article showing the delicate signaling pathways from senescent skin microenvironments in association with external stressors, such as UVR, microbiome, and PM. α-MSH, α-melanocyte stimulating hormone; AhR, Aryl hydrocarbon receptor; AP-1, Activator protein 1; ATG, Autophagy related; CCL2, C-C motif chemokine ligand 2; CREB, Cyclic AMP-responsive element-binding protein; DCs, Dendritic cells; DNMT, DNA methyltransferase; ECM, Extracellular matrix; ERK, Extracellular signal-regulated kinase; ET, Endothelin; H2AX, H2A histone family member X; IGF, Insulin-like growth factor; IL, Interleukin; JNK, c-Jun N-terminal kinase; LCs, Langerhans cells; LN, Lymph node; MAPKAPK2, MAP kinase Activated Protein Kinase 2; MAPKs, Mitogen-activated protein kinases; MITF, Microphthalmia-associated transcription factor; MMPs, Matrix metalloproteinases; MNPs, Mononuclear phagocytes; mTOR, Mammalian target of rapamycin; NF-κB, Nuclear factor kappa-light-chain-enhancer of activated B cells; PD-1, Programmed cell death protein 1; PKA, Protein kinase A; PM, Particulate matter; POMC, Pro-opiomelanocortin; ROS, Reactive oxygen species; SASP, Senescence-associate secretory phenotype; SCF, Stem cell factor; SDF-1, Stromal cell-derived factor-1; TGF, Tumor growth factor; Th cells, T helper cells; TNF-α, Tumor necrosis factor- α; TRM, Tissue-resident memory T cell; UV, Ultraviolet light; YBX-1, Y-Box Binding Protein 1.