Horm Mol Biol Clin Invest 2013
Georgios Nikolakis, Evgenia Makrantonaki and Christos C. Zouboulis*
Abstract: Aged skin exhibits disturbed lipid barrier, angiogenesis, production of sweat, immune functions, and calcitriol synthesis as well as the tendency towards development of certain benign or malignant diseases. These complex biological processes comprise endogenous and exogenous factors. Ethnicity also markedly influences the phenotype of skin aging. The theories of cellular senescence, telomere shortening and decreased prolifera-tive capacity, mitochondrial DNA single mutations, the inflammation theory, and the free radical theory try to explain the biological background of the global aging pro-cess, which is mirrored in the skin. The development of advanced glycation end-products and the declining hormonal levels are major factors influencing intrinsic aging. Chronic photodamage of the skin is the prime factor leading to extrinsic skin aging. The deterioration of important skin functions, due to intrinsic and extrinsic aging, leads to clinical manifestations, which mirror several internal age-associated diseases such as diabetes, arterial hyper-tension and malignancies.;
Keywords: aging; extrinsic aging; hormones; intrinsic aging; skin.;
*Corresponding author: Prof. Dr. Christos C. Zouboulis,;
Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Auenweg 38, 06847 Dessau, Germany,;
Georgios Nikolakis: Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, 06847 Dessau, Germany
Evgenia Makrantonaki: Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, 06847 Dessau, Germany;
and Forschungsgruppe Geriatrie, Charité Universitaetsmedizin Berlin, 13347 Berlin, Germany
It is a common truth that biological systems stand as a natural paradox, which in the past was considered to defy the Second Law of Thermodynamics, stating that the entropy of every isolated system should always increase. The existence and maintenance of these systems are based on the development of biochemical mechanisms, with which they struggle to evade or at least delay oxidation that would eventually lead to a lower energy state [1–3]. Under this spectrum, aging can be considered as a natural process of biochemical events, leading to gradual accumulation of damage and resulting in disease and death . Although the manifestations of this damage are masked as far as the inner organs are concerned, the skin surface appears as the first bearer of marks of time as well as an easily accessible model for the assessment and determination of the involved molecular mechanisms . Skin has long been recognized to protect organisms against deleterious environmental factors and is vital for the homeostasis of temperature, electrolyte, and fluid balance of the body .
Phenotype of skin aging
Aged skin shows a phenotype of a disturbed lipid barrier, angiogenesis, production of sweat, immune functions, and production of calcitriol as well as the tendency towards development of various benign or malignant diseases . These complex biological processes comprise endogenous factors such as genetic predisposition, cellular metabolic pathways, and qualitative and quantitative hormonal alterations, termed intrinsic aging and exogenous factors, primarily ultraviolet (UV) light exposure and secondarily chemicals, toxins, and pollution, leading to extrinsic aging . The model for the former is skin deriving from areas that are not sun-exposed, mostly the inner side of the upper arm and the buttocks, and for the latter are skin areas constantly sun-exposed, such as facial skin. Intrinsically aged skin appears macroscopically thin and atrophic and exhibits fine wrinkles, loss of underlying fat, reduced elasticity, and prominent dryness, often accompanied by pruritus . On the contrary, extrinsically photoaged skin exhibits deep wrinkles, thickening of the epidermis, dullness, roughness, and mottled discoloration. Telangiectasies and pigmentary discoloration might also be observed in advanced and severe degrees of photoaging [9–14], with the latter being the major skin aging-associated change in Asian populations .
The latter observation led to comparative studies between populations of different ethnicity. Caucasians have greater skin wrinkle formation and sagging in comparison with other skin phenotypes, whereas the manifestations have an earlier onset . Furthermore, Caucasians are more prone to skin desquamation, which is dependent of age . Afro-American and Caucasian women both have a higher prevalence of age-related dryness compared to other ethnicity groups . Chinese women have more severe periorbital wrinkles in comparison with women from Japan, whereas Thai women were characterized by severe wrinkling of the lower half of their faces . Caucasian females have a higher prevalence of sagging in the subzygomatic area . Wrinkling in each facial area has a later onset in Chinese women in comparison with French women, although age-related pigment spot intensity is the cardinal sign of aging in Chinese women . Lastly, although Asian skin seems to have similar transepidermal water loss and ceramide levels to Caucasian skin, the stratum corneum barrier appears to be more susceptible to mechanical stimuli. Asian skin is more sensitive to exogenous chemicals because of the thinner stratum corneum barrier, higher eccrine gland intensity, and smaller pore areas in comparison with other ethnic groups, indicating the correlation of the latter to the sebaceous gland activity . Because skin aging phenotype varies according to the population, not universal but ethnicity-specific aging characteristics could only be correlated with age-associated diseases. Photographic severity scales and other clinical methods are developed to assess the severity of skin aging features [9, 20].