**7. Effects of aging on extracellular matrix**

ECM comprises of a network of numerous molecules and primarily functions to provide support to cells. It presents the cells with growth factors which in turn bind their respective receptors to influence response of the cells to various stimulus. Moreover, the matrix present around a cell also protects it from any possible mechanical injury [60, 61].

Depending upon specific function and anatomical position, ECM organization may differ. Exposure to UVR can adversely affect this particular organization. One instance involves the fragmentation of long collagen fibrils into short chains along with accumulation of unstructured elastin containing material which terminates in decreased skin durability [62]. Deposition of fragmented collagen fibrils can further result in decreased formation of type I procollagen [63]. Another effect UVR have is the production of MMPs that function as ECM scissors. Continued exposure to UVR results in elastin fiber injury which can terminate in wrinkle formation. In skin, elastin fibers are classified as oxytalan fibers, elaumin fibers and dermal elastin fibers depending upon their structure and position [64]. They form a network that is prone to elastase secreted from UV exposed fibroblasts and neutrophils. Fibroblast elastase can digest elaumin and oxytalan fibers while neutrophil elastase is able to digest all three elastin fibers which is crucial especially during inflammation and damage recovery. But since the numbers of neutrophils is low in dermis, major damage is contributed by fibroblast elastase which culminate in wrinkles [65, 66].

Another hallmark of photoaging involves decreased proteoglycan content [67]. Hyaluronan degradation in UV irradiated skin occurs due to increased HYBID protein activity. Large hyaluronan molecules bought inside the cell in clathrin coated vesicles

are broken down into smaller components and released into the external surrounding. These hyaluronan components act as inflammatory signals and can additionally lead to wrinkle formation [68].

ECM remodeling generally involves uptake of degraded collagen fibers inside fibroblasts via receptors like integrin α2β1 and Endo180 receptor. Endo180 receptor belongs to type I membrane protein occurring in the plasma membrane. It binds to type I, IV and V collagen to internalize them inside the cell. Few studies regarding endo180 receptor and photoaging have shown that cells exposed to UVR have low endo180 receptor expression which ultimately results in decreased internalization of collagen fragments. Additionally, IL-1α secretion from keratinocytes under UV exposure blocks endo180 receptor expression. Further investigations regarding endo180 receptor expression in photoaged skin are worth undertaking in the future [69, 70].
