Mechanisms of Senescence and Anti-Senescence Strategies in the Skin
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. Skin Morphology
1.1.1. Epidermis
Cell Populations of the Epidermis
1.1.2. Dermal–Epidermal Junction
1.1.3. Dermis
1.1.4. Hypodermis
1.2. Skin Aging
1.2.1. Intrinsic Aging
1.2.2. Extrinsic Aging
1.2.3. Clinical Aspects of Skin Aging
1.2.4. Histopathological and Ultrastructural Features of Intrinsic and Extrinsic Skin Aging
1.2.5. Dermatoporosis: A Particular Form of Skin Aging
1.3. Cellular Senescence
1.3.1. Senescence in Skin Cells
Methods for Induction of Cellular Senescence
1.3.2. Investigation of Aging In Vivo
1.4. Senescent Cells: A Novel Therapeutic Target for Skin Aging
1.5. Discussion
Author Contributions
Funding
Conflicts of Interest
References
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Category | SASP Factors | Cell Types (That Mainly Express These SASP) |
---|---|---|
Interleukins | IL-1, IL-1b, IL-6, IL-7, IL-13, IL-15 | Fibroblasts, Keratinocytes & Melanocytes |
Chemokines | IL-8, GRO-a, GRO-b, GRO-g, MCP-2, MCP-4, MIP-1a, MIP-3a, HCC-4, eotaxin-1, eotaxin-3 | Fibroblasts, Keratinocytes and Melanocytes |
Insoluble factors | Fibronectin, collagens, laminin | Fibroblasts & Keratinocytes |
Inflammatory molecules | TGFβ, GM-CSE, G-CSE, IFN-g, BCL, MIF | Keratinocytes. TGFβ and G-CSE are also secreted from fibroblasts, GM-CSE from macrophages, IFN-g from T-cells, BCL from lymphocytes and MIF from macrophages |
Non-protein molecules | ROS, NOS, miRNAs | Keratinocytes and Fibroblasts. ROS are also secreted from melanocytes, NOS from endothelial cells and miRNAs from melanocytes |
Growth factors and regulators | EGF, bFGF, HGF, KGF, VEGF, SCF, SDF-1, PIGF, NGF | Fibroblasts and Keratinocytes |
Receptors and ligands | ICAM-1, ICAM-3, OPG, sTNFRI, sTNFRII, TRAIL-R3, Fas, uPAR, EGFR | Fibroblasts and Keratinocytes |
Proteases and regulators | MMP1, MMP3, MMP10, MMP12, MMP13, MMP14, TIMP1, TIMP2, PAI1, PAI2 | Fibroblasts, Keratinocytes and Macrophages |
Compound | Target | Disease | Effect | References |
---|---|---|---|---|
Dasatinib + Quercetin | Inhibition of prosurvival pathways | Idiopathic pulmonary fibrosis (IPF) Systemic sclerosis (SSc) Persistent physical dysfunction | Senolytics Reduce SASP factors in humans and the adipose tissue senescent cell burden and in mice reduce senescent cells | [167,169,170] |
ABT-263 & ABT-737 | Block the interaction of BCL-2, BCL-XL, BCL-W with BCL-2 homology domain containing proapoptotic proteins | DNA damage in lungs Aged epidermis | Senolytics Elimination of senescent cells in mice | [158,202,203] |
FOXO4-DRI | Blocks the interaction of FOXO4 and p53 | Aging | Senolytic Eliminates senescent human fibroblasts and chondrocytes in vitro and senescent cells in mice | [175,204] |
Fisetin | Antioxidant | Progeroid syndrome Skin damage from UV exposure | Senolytic Decreases specific types of senescent cells in murine models and in human adipose tissue explants | [171,205] |
Geldanamycin | HSP90 inhibitor | Aging | Senolytic In human cells and in mouse models delayed age-related co-morbidities | [206,207] |
Panobinostat | Histone deacetylase inhibitor | Upper aerodigestive and lung malignancies | Senolytic In vitro kills senescent cells that accumulate during chemotherapy | [208] |
Metformin | Prevention of oxidative stress | Stress-induced senescence of adipose derived stromal cells | Senomorphic In human cells decreases senescence and SASPs | [209] |
Rapamycin | Target mTORC1 | Cellular senescence | Senomorphic Reduces senescence and SASPs in cell lines from human, mouse and rat | [158] |
SB203580 | p38MAPK inhibitor | Senescence caused by irradiation | Senomorphic Reduces the secretion of SASP in mice | [210] |
Procyanidin C1 | Inhibition of SASP or induction of mitochondrial dysfunction | Aging and age-related diseases | Senolytic and senomorhic At low concentrations reduce the SASP, whereas in higher concentrations promotes the production of ROS | [198,199] |
Rutin | Weakens the interaction between ATM and TRAF6 | Cellular senescence | Senomorphic Reduces the expression of SASP | [211] |
Niacinamide & Hyaluronic acid | Antioxidant Anti-inflammatory Immunomodulatory | Skin aging | Senomorphic Reduces the expression of SASP | [212] |
Polyphenolic Flavonoids | Targeting of regulatory pathways (such as p38 signaling pathway, PI3K/Akt, mTOR and JAK/STAT) or the expression of transcription factors or directly SASP factors | Age-related diseases | Senomorphic Reduces the expression of SASP | [213] |
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Konstantinou, E.; Longange, E.; Kaya, G. Mechanisms of Senescence and Anti-Senescence Strategies in the Skin. Biology 2024, 13, 647. https://doi.org/10.3390/biology13090647
Konstantinou E, Longange E, Kaya G. Mechanisms of Senescence and Anti-Senescence Strategies in the Skin. Biology. 2024; 13(9):647. https://doi.org/10.3390/biology13090647
Chicago/Turabian StyleKonstantinou, Evangelia, Eliane Longange, and Gürkan Kaya. 2024. "Mechanisms of Senescence and Anti-Senescence Strategies in the Skin" Biology 13, no. 9: 647. https://doi.org/10.3390/biology13090647