A wrinkle is a fold, ridge or crease in the skin. Different intrinsic and external factors cause the development of a wrinkle. Biochemical and histological studies has revealed the pathogenesis

of wrinkles. Significant biochemical changes contributed to the formation of wrinkles. These include but not limited to –

1. In epidermis: the decrease of:

• markers of cellular differentiation
• Filaggrin (a filament-associated protein that binds to keratin fibers in epithelial cells)
• keratohyalin granules (a protein structure found in granules in the stratum granulosum of the epidermis, which may be involved in keratinization)
• enzyme transglutamase I (Transglutaminases form extensively cross-linked, generally insoluble protein polymers that are indispensable to create barriers and stable structures in skin)

These components are essential for the maturation of corneocytes (the keratinocytes in their last stage of differentiation and form the outermost part of the epidermis) and deficiencies in barrier function would produce water loss and desquamation (shedding of the outermost layer of the skin) defects.

• epidermis is thinner and has reduced rete pegs/rete ridges in naturally aged skin; but is often thickened in photodamaged skin.

2. At DermoEpidermal junction – the decrease of

• collagens IV and VII
• oxytalin fibers (By light microscopy three different types of fibers were observed in skin: oxytalan, elaunin, and elastic – forming the elastic system of skin, The oxytalan fibers are the most superficial ones – they are very thin and directed perpendicularly to the dermoepidermal junction. At the electron microscopic level the oxytalan fibers are formed by bundles of tubular microfibrils)

These components contributed to weakening the interface between Dermo-Epidermal Junction

3. In the Dermis, the decrease of

• glycosoaminoglycans vary in distribution around the wrinkled area
• chondroitin sulfate in papillary dermis

These components are the natural want-binding agents in the extracellular matrix (the ground substance) working like sponges to maintain the water content of the skin. Hydration is a factor in wrinkling.

Histological changes are significant in dermis connective tissue

• collagen fiber bundles are shorter and thinner and have more space between the fiber bundles. collagen fragmentation is evident
• structural changes in elastic fibers; build-up of elastotic material in photodamaged skin (elastosis)

It has been widely accepted that the damage of skin connective tissue in the dermis – collagen fragmentations and elastosis (decreased elasticity due to loss of elastin) is the main mechanism of wrinkle formation.

4. Subcutaneous, the change of

• fat loss
• slackening of facial muscles

The facial muscles are subcutaneous muscles that generally originate on bone, and insert on the skin (dermis) of the face. When the facial muscles contract, the muscle shortens without a corresponding shortening of skin, thereby producing a wrinkle.