nemoci-sympt/DERMATOLOGIE/vrasky/patofyziologie
Skin aging
Endogenous aging
- Passage of time, hormonal decline, and telomere shortening
Exogenous aging
- Exposure to ultraviolet radiation,
- Trauma,
- Chemical substances
- UV light displayed the most significant impact on skin aging - photoaging
Photoaged skin
- Deepening wrinkles,
- Sagging,
- Roughness,
- Scaling,
- Increased fragility,
- Patchy pigmentation changes,
- Dilated blood vessels,
- Compromised wound healing,
- Benign and malignant proliferation
Expression of matrix metalloproteinases
- Collagen synthesis and degradation triggered by exposure to light
- Fundamental approach to
- Tackle this issue is to diminish MMP levels
- Regulate collagen secretion.
MMPs
- Group of zinc-containing endopeptidases
- Tissue remodeling and degradation of proteins in the extracellular matrix
- Regulatory role in cell proliferation, migration, and differentiation
- Apoptosis, angiogenesis, tissue repair, and immune response
- MMPs primarily contribute to collagen degradation in the extracellular matrix
- Visible signs of aging, including wrinkles, sagging, and loss of skin elasticity
- Exposure to UV radiation significantly upregulates MMP expression
- Leading to disrupted MMP activity in human skin tissues
- Research of the "skin anti-aging medications that target MMPs"
- Standard structure of MMPs typically consists of
- An approximately 80-amino acid prepeptide
- Catalytic metalloprotein structural domain spanning around 170 amino acids
- A variable-length junction peptide
- UV-induced photoaging primarily encompasses
- Oxidative stress, DNA damage, inflammatory response,
- Collagen degradation, and other related factors
- Oxidative damage exerts an influence on the expression of signaling kinases in skin tissues
Glycosaminoglycans (GAGs)
- Large linear polysaccharides, and are a major component of the ECM.
- Chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS), heparan sulfate (HS), heparin (HP), and hyaluronic acid (HA)
- Except HA, GAGs
- Contain sulfate substituents at different positions on the chain
- Heavily glycosylated on their related proteoglycan (PG) core proteins
- HA
- Is not sulfated and does not attach to proteins to form proteoglycans.
- Binds to proteins containing HA-binding domain
- GAG chains contain numerous negatively charged carboxyl and sulfate groups
- May have important roles in maintaining the water content in tissue
- Crosslinking of HA with matrix proteins such as the collagen network
- Results in the formation of supermolecular structures
- Increases tissue stiffness
- Dermal HA
- Mainly produced by fibroblasts
- Abundant in the papillary dermis
- Crosslinks with other ECM proteins, like collagen
- Resulting in increased tissue stiffness
- Space filling and shock-absorbing roles
- Intrinsically aged skin
- HA binding proteins (HABPs) are reduced compared with in young skin
- Level of HA itself is not significantly different
- HABPs
- Trigger several intracellular signaling pathways
- Regulating proliferation, migration, and differentiation
- Dermal HA content in photoaged skin
- Is significantly increased
- Particularly in regions of solar elastosis
- Although UV irradiation induces HA synthase (HAS)
- HAS mRNA levels in aged sun-exposed skin
- Were significantly reduced compared to those in sun-protected skin
- Increased HA in photoaged skin might be the result of abnormal accumulation of nonfunctional proteins
- Total sulfated GAGs
- Decreased during intrinsic aging
- May be specific to each type of sulfated GAGs
- HS and CS decrease
- KS and DS increase
- Photoaged skin
- Total sulfated GAGs increased, similarly to HA
Proteoglycans - PGs
- Are a family of GAG conjugated proteins
- Essential for maintaining the mechanical strength of the skin
- Decorin, biglycan, and versican
- The most abundant proteoglycans in human skin.
- Photoaged skin
- Versican seems to be increased,
- Biglycan does not change,
- Decorin is absent
- Intrinsic aging,
- Elastic fibers is reduced;
- Extrinsic aging
- Nonfunctional, abnormal elastic fibers accumulate in the papillary dermis
