Skin aging (overview) L98.8

The skin aging process is essentially composed of 2 processes:

• Biological or endogenous ageing (ageing) also intrinsic skin ageing
• environmental ageing or exogenous ageing (especially light ageing) also extrinsic skin ageing

Polyätiological endogenously and exogenously induced process. To be discussed:

• Metabolic changes (such as the irreversible accumulation of Advanced Glycation Endproducts - AGEs). AGEs are bioactive molecules that can serve as a strong and independent predictor of atherosclerosis and cardiovascular mortality in diabetics and hemodialysis patients.
• UV-induced inflammatory reactions, such as those initiated by the activated acrylic hydrocarbon receptor.
• Genetic alterations (dysregulation of the insulin and STAT3 signaling pathway; upregulation of proaptotic genes, alteration of cytoskeletal genes such as keratin 2A, 6A, and 16A).
• Free radical damage (especially membrane damage due to lipid peroxidation). Origin of free radicals (see below oxidative stress): endogenous from mitochondrial respiration, enzymatic reactions (oxidases), arachidonic acid metabolism, phagocytosis processes or exogenous by food, drugs, environmental toxins, UV light.
• Alteration of the Wnt signaling pathway (regulated by various processes in embryonic development and can lead to tumour formation) is suppressed both on RNA and protein level.
• Influences of reduced hormone levels.

Investigations on best. Progeria syndromes show that best. important biological processes such as DNA replication, recombination, repair and transcription - as well as mitochondrial functions, cell cycle and apoptosis play an important role in skin ageing.

Furthermore, the skin ageing process is negatively influenced by infrared irradiation, nicotine abuse or environmental pollution (e.g. fine dust pollution).

• General: Reduction of turgor and blood circulation, reduced production of sebum and sweat glands, tendency to desiccation, reduced subcutaneous fatty tissue, diluted dermis, pigmentary shifts ( lentigo solaris, hypomelanosis guttata idiopathica), benign and malignant neoplasms ( verrucae seborrhoicae, telangiectasias, basal cell carcinomas, spinocellular carcinomas), increased capillary fragility and vulnerability ( purpura senilis, pseudocicatrices stellaires), elastosis in light exposed areas ( cutis rhomboidalis nuchae, M. Favre-Racouchot).
• Aged skin: smooth, hardly any skin lesions, accentuation of mimic wrinkles (water loss), little loss of elasticity.
• Skin that has been lightly aged: leathery aspect, pigmentary changes, widespread formation of deep wrinkles, considerable loss of elasticity.

• Combinations of various therapies are possible and useful.
• Prophylaxis through antioxidants systemically (vitamin A, beta-carotene, vitamin E, vitamin C) or locally, skin care, sun protection, avoidance of nicotine and excessive UV exposure.
• Tretinoin and isotretinoin creams, chemical peeling with peeling substances such as salicylic acid, trichloroacetic acid or fruit acids (AHS).

1. Kusserow A et al (2005) Unexpected complexity of the Wnt gene family in a sea anemone. Nature 433:156-160.
2. Makrantonaki E (2015) Skin aging. Dermatologist 66: 730-737
3. Si Tao et al (2015) Wnt activity and basal niche position sensitize intestinal stem and progenitor cells to DNA damage. EMBO J doi: 10.15252/embj.201490700.
4. Spanjer AI et al (2016): TGF-β-induced profibrotic signaling is regulated in part by the WNT receptor Frizzled-8 FASEB Journal doi: 10.1096/fj.201500129
5. Uribarri J et al(2007): Circulating glycotoxins and dietary advanced glycation endproducts: two links to inflammatory response, oxidative stress, and aging. J Gerontol A Biol Sci Med Sci 62: 427-433.
6. Vierkötter A et al (2010) Airborne particle exposure and extrinsic skin aging. J Invest Dermatol 130:2719-2726.