Focus on the Contribution of Oxidative Stress in Skin Aging

Abstract

Skin aging is one of the most evident signs of human aging. Modification of the skin during the life span is characterized by fine lines and wrinkling, loss of elasticity and volume, laxity, rough-textured appearance, and pallor. In contrast, photoaged skin is associated with uneven pigmentation (age spot) and is markedly wrinkled. At the cellular and molecular level, it consists of multiple interconnected processes based on biochemical reactions, genetic programs, and occurrence of external stimulation. The principal cellular perturbation in the skin driving senescence is the alteration of oxidative balance. In chronological aging, reactive oxygen species (ROS) are produced mainly through cellular oxidative metabolism during adenosine triphosphate (ATP) generation from glucose and mitochondrial dysfunction, whereas in extrinsic aging, loss of redox equilibrium is caused by environmental factors, such as ultraviolet radiation, pollution, cigarette smoking, and inadequate nutrition. During the aging process, oxidative stress is attributed to both augmented ROS production and reduced levels of enzymatic and non-enzymatic protectors. Apart from the evident appearance of structural change, throughout aging, the skin gradually loses its natural functional characteristics and regenerative potential. With aging, the skin immune system also undergoes functional senescence manifested as a reduced ability to counteract infections and augmented frequency of autoimmune and neoplastic diseases. This review proposes an update on the role of oxidative stress in the appearance of the clinical manifestation of skin aging, as well as of the molecular mechanisms that underline this natural phenomenon sometimes accelerated by external factors.

Keywords: UV; aging; dermis; epidermis; inflammation; melanocyte; photoprotection; skin; skin cancer.

Figure 1

A schematic representation of the structure and functions of the skin. Human skin is composed of three layers: the epidermis (the top layer), the dermis (the middle layer), and the hypodermis (the bottom fatty layer).

Figure 2

Age-related changes in the skin. Skin aging results in cumulative detrimental effects characterized by abnormal ECM organization, pigmentary changes, loss of subcutaneous fat, hair greying, minored hair density, decreased sebaceous gland function, and low-grade chronic inflammation. Cellular and molecular events reviewed in the text describe the impact of oxidative disequilibrium on these time-dependent and/or extrinsically accelerated tissue transformations.

Figure 3

The involvement of oxidative stress in the greying process. In young and healthy subjects, melanocytes in pigmented hair follicles can deal with the low endogenous oxidative stress caused by the melanin biosynthetic pathway. This is due to the adequate presence of endogenous antioxidant levels and the high DNA repair activity. In old subjects, however, reduced production of endogenous antioxidants and repair enzymes induce deleterious oxidative stress damage in pigment-producing cells. This results in the accumulation of senescent inactive melanocytes around the dermal papilla and at the outer root sheath, no melanocyte stem cells at the bulge area, and consequent a non-pigmented hair shaft.

Figure 4

Schematic representation of the involvement of oxidative stress in common age-related skin diseases. Progressive structural and functional degeneration of the skin leaves it prone to a wide variety of very common cutaneous diseases. The onset of most of these clinical conditions involves extrinsic activation of cutaneous immune cells in a redox-dependent manner. This includes a reduced immune response, production of autoantibodies, and chronic low-grade inflammation. Structural, biochemical changes, accumulation of senescent cells, and age-related stem cell depletion impact the cutaneous repair capacity. Metabolic alterations in aged skin do not fully support the physiological function of the skin and its appendages.