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Wrinkles form from loss of collagen and elastin around the thin eyelid skin, and squinting and smiling contribute to crow's feet around the eyes High UV exposure from squinting: Squinting in sunlight concentrates the orbicularis oculi contraction while simultaneously exposing the delicate periocular skin to UV without the protection people typically apply to other facial areas Thin vascular walls: The periocular area's thin skin makes underlying blood vessels more visible the purplish discoloration of dark circles is largely the color of these vessels showing through transparent skin Crow's feet form through a specific mechanism: the orbicularis oculi muscle contracts the overlying skin folds over years of repetition, the collagen fibers in the fold zone degrade and the crease becomes permanent even without muscle contraction

A 2013 Cochrane review performed on 52,044 randomized participants showed limited positive effects of the MedDiet on cardiovascular risk (66), whereas in the same year a meta-analysis performed on 3,073 randomly assigned individuals with different dietary regimes showed that the MedDiet as well as diets characterized by low-glycemic index, low-carbohydrate and high-protein determined an improvement in cardiovascular risk factors in patients with diabetes (67)

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Aptamers, single-stranded DNA or RNA with unique three-dimensional conformations, tightly bind to target proteins, offering promise for targeted O-GlcNAc modification on specific proteins [197]