**10. Future perspective and challenges**

Recently, role of cathepsins with respect to photoaging has been pursued to a greater extent. Cathepsins have important functions in ECM maintenance, apoptosis,

#### *Skin Aging: Implications of UV Radiation, Reactive Oxygen Species and Natural Antioxidants DOI: http://dx.doi.org/10.5772/intechopen.100102*

cell proliferation and differentiation among others. Thus, cells maintain a tight regulation of cathepsins that is hampered during the photoaging process. A study reported diminished levels of cathepsins B, D and K whereas cathepsin G was upregulated in the photoaged skin. Cathepsin G in turn could increase various MMP expression [117]. Such imbalance in cathepsin regulation can have strong adverse effects on the autophagy process. Several studies have shown that autophagosomes of photoaged cells display an upregulation of p62, downregulation of cathepsin L, limited degradation of LC3II protein and an unchanged expression of Beclin-1. All these changes hint towards the reduced lysosomal ability towards degradation of unwanted products [118].

Another area that has received abundant attention involves formation of advanced glycation end products (AGE). They are produced when various proteins undergo oxidation followed by glycation and get accumulated in tissues with advancing age, although they are also found in UVR exposed skin. This occurs as a result of decreased cathepsin D levels which is essential for AGE degradation inside the cell [119, 120].

With advancement in molecular field, several investigations have also concentrated on miRNA expression in terms of chronological aging and photoaging [121]. Specifically, sharp changes in miR-34 and miR-29 family regulation have been reported. For instance, increased miR-34b-5p expression in aged dermis has been reported for decreased COL1A1 and elastin expression together with increased MMP-1 expression [122].

These investigations mentioned above, only portray a fraction of the whole story required for understanding the aging process including both intrinsic and extrinsic aging. Various questions yet await their answers regarding aging. Due to the blurred line between photoaging and chronological aging, differentiating characteristics of these two aging types is often approached with confusion. This occurs because variation with respect to skin aging in different individuals is often subject to photoaging locations, natural skin pigmentation and exposure time period among the other factors. Challenges concerning antioxidants have also been proposed by many authors. Antioxidant level in the skin is affected by oxidative stress along with diet of an individual. To alleviate the signs of photoaging, exogenous supplementation of antioxidants can be given either by extrinsic application in the form of topical creams or intrinsic/systemic application in the form of tablets or capsules. Both the forms of supplementation have their own set of drawbacks and advantages [123]. Moreover, in case of plant derived antioxidants, different parts of the plant have different expression levels of a particular bioactive compound that acts as antioxidant. This forms an important factor while extracting particular antioxidants.

Apart from these challenges, a more daunting analysis that can be made is that radiation whether UV, visible or infrared can adversely affect the skin. To combat this problem various sunscreen formulations are used. But till now, most sunscreen formulations provide protection against specific wavelength ranges of UV region only. This shows the need for formulation of sunscreens which provide a broader protection [124].

### **11. Conclusions**

Aging is a part of life. It is a complex process, affected by both intrinsic and extrinsic factors. Further addition of photoaging process induced by UVR makes studying aging and taking protective measures against it more complex. Therefore, alleviating

aging signs is still in requirement of more innovative ideas that are expected to be developed with more knowledge about the various mechanisms involved under aging and important investigations that can further shed light onto this phenomenon.
