Photoaging: New insights into its stimulators, complications, biochemical changes and therapeutic interventions

Abstract

Human beings are constantly exposed to UV radiations emitted by sun. Prolonged exposure to UV radiations initiates a series of pathophysiological events that account for photodamage in skin. Photoaging is the major contributor of skin melanoma and risk is particularly seen higher in fair skin population, with approximately 80 to 90% of European and North American population prevalent to skin photoaging. Importantly, skin cancer due to sun exposure is the most leading type of cancer prevalent in New Zealand; with approximately 67,000 new cases diagnosed every year with skin cancer. In fact, photoaging-associated skin cancer accounts for more than 65,000 deaths worldwide every year. This current and impending burden of the affected individuals provokes the need for further insight into the biochemical changes that contribute to the pathogenesis of skin cancer due to UV radiations and future therapeutic interventions to prevent and treat the associated skin disorders. On exposure to UV radiation, there is the generation of reactive oxygen species, reactive nitrogen species and inflammatory mediators. It also increases DNA damage in the body. All these factors together lead to degradation of collagen, and finally results in formation of wrinkles and angiogenesis which are the major clinical manifestations of photoaging. Further, UV radiations cause decrease in Langerhans cell, melanocyte, keratinocytes, fibroblast, collagen, tissue inhibitor of matrix metalloproteinase, various endogenous antioxidants and increase in level of various cytokines. Therefore, by understanding the molecular mechanisms underlying photoaging, new therapeutic managements can be identified and discovered.

Introduction

Aging is a multifactorial and complex process resulting in functional decline and mortality of the cells and organism [1]. There are mainly two types of aging: intrinsic aging and extrinsic aging. Intrinsic aging is an uncontrollable process. Aging increases as the age increases which causes decrease in functional capacity of the body over a time. Intrinsic aging can be manifested by fine wrinkles, thin and transparent skin, hollowed cheeks and eye sockets, loss of firmness on the hands and neck, sagging, dry skin that may itch, inability to sweat sufficiently, greying of hairs that on long-term turns white, and hair loss [2]. Extrinsic aging mainly occurs because of various environmental factors such as various and repetitive facial expressions, gravity, sleeping position, temperature, humidity, and smoking and mostly because of repetitive exposure to sun [2], [3].

In present condition, large amount of ultraviolet radiation is coming on the earth because of a breach in the ozone layer, which is preventing ultraviolet radiation to coming on earth by absorbing it. Since skin is the outermost layer of the body, it is mainly affected by the harmful effects of UV radiation. UV radiation is mainly divided in three parts: UVA (320–400 nm), UVB (280–320 nm), UVC (< 280 nm). Out of these, UVA and UVB are known to produce harmful effects to the skin [4].

Aging of the skin by ultraviolet radiation is known as photoaging. The term photoaging came into existence in 1980 [5]. Repeated exposure of ultraviolet radiation leads to photoaging. The symptoms of photoaging are mainly produced because of biochemical and morphological changes that occur in the body on repeated exposure to radiation. Chronic UV exposure cause decrease in efficacy of the body to combat oxidative stress, generation of interleukins, TNF-α, different growth factor receptors, activation of NF-kB and MAPK pathway, decrease in TGF, etc. [6].

Photoaging is the leading cause of skin cancer or melanoma and is particularly seen higher in fair skin population. Indeed, low ozone levels in the atmosphere, outdoor lifestyle, increasing intermittent sun exposure during childhood, hereditary makeup and fair skin are the major contributing factors in skin cancer due to UV radiations and that is a reason why population in New Zealand, Europe and America are more susceptible to this condition [7]. Recent evidence suggests that 80 to 90% of European and North American population are prevalent to skin photoaging [8]. Importantly, skin cancer due to sun exposure is the most leading type of cancer prevalent in New Zealand; with approximately 67,000 new cases diagnosed every year with skin cancer [9]. Also, the global prevalence of skin cancer due to photodamage is significant. The World Health Organization estimates that more than 65,000 people worldwide die from skin cancer every year due to UV irradiations [10]. This current and impending burden of the affected individuals provokes the need for further insight into the biochemical changes that contribute to the pathogenesis of skin cancer due to UV radiations and future therapeutic interventions to prevent and treat the associated skin disorders.

This review is mainly focused on the different stimulators involved in the pathogenesis of photoaging, the biochemical alterations that occurs during photoaging and the therapeutic implications that can be exploited to combat the devastating effects of photoaging. A literature search was performed using PubMed to look for relevant articles. The keywords used for search were UV radiation, photoaging and skin cancer. The articles were finally screened for further compilation of the present work.