Chapter 2

Aging and the Recovery of Skin Function and Appearance

Adele Sparavigna,    Clinical Research and Bioengineering Institute, Monza, Italy

Abstract

Age-related skin changes (wrinkles, atrophy, gray spots, loss of hydration, and elasticity) can be considered the result of intrinsic factors (chronological, hormonal, and genetic) and the consequence of life habits and environmental damage mainly due to ultraviolet radiation from the sun (responsible for skin photoaging). The correlation between diet and skin is well established in some skin diseases (acne, atopic dermatitis, and psoriasis are a few examples). What is not yet entirely clear is what substances can improve skin appearance and aging for a person who is well nourished. Thanks to the analysis of recent scientific literature and my experience as a dermatologist and researcher, I will try to investigate the role of diet in counteracting skin aging by focusing on the Mediterranean dietary profile, which is characterized by the regular use of abundant fruits, vegetables, wholemeal bread and cereals, legumes, nuts, seeds, and olive oil, all of them fresh, natural, seasonal, and locally sourced.

Keywords

Skin aging; Mediterranean diet; antioxidant food; nonenzymatic glycation products; phytoestrogens; telomere shortening

Introduction

Aging can be defined as a physiological process characterized by a continuous and irreversible loss of homeostasis that involves the whole body. With the progressive increase of life expectancy in developed countries, the prevalence of aging-related diseases is increasing, making it necessary to implement specific preventive strategies. The leading role of diet in maintaining health throughout the human life cycle has been well established by a multitude of scientific papers from different medical disciplines. The effects of an unbalanced diet can be detected at different levels: diets rich in saturated fats, cholesterol, and animal protein or high in salt and sugar can not only increase metabolic and cardiovascular disease risk but also contribute to the accumulation of oxidative and inflammatory responses, increasing the production of free radicals that damage all cellular constituents and lead to an acceleration in the aging process. Skin, as an integral part of the system, is affected by these responses. Wrinkles, atrophy, gray spots, and loss of hydration and elasticity are the most visible signs. To understand how diet contributes to the maintenance of skin health is particularly relevant because skin aging is determined by the combined influences of intrinsic factors (chronological, hormonal, and genetic) and extrinsic ones that can be divided in behavioral factors such as sun exposure (responsible for photoaging), cigarette smoking, diet, alcohol drinking, drug abuse, and environmental factors such as pollution, weather, and humidity.

The correlation between diet and skin health was recently well established for several skin diseases. Examples include acne (especially for milk and dairy products, which have been correlated in several studies with more severe diseases) (Melnik, 2015), atopic dermatitis (which improves with the intake of essential fatty acids and certain probiotics) (Mohajeri and Newman, 2014), and psoriasis (which is significantly correlated with metabolic syndrome) (Voiculescu et al., 2014). Correcting poor and unbalanced nutrition undoubtedly improves skin health, but what is not yet entirely clear is what substances can improve skin health and appearance and counteract skin aging in a targeted manner for a person who is well nourished. Thanks to the analysis of recent scientific literature and my personal experience as a dermatologist and researcher, I will try to investigate these issues, focusing on the traditional feeding practices of Italy, my home country, which are most famously represented by the Mediterranean diet.

Skin Aging

As far as skin is concerned, the aging phenomenon is caused by exogenous and endogenous factors. Ultraviolet (UV) radiation exposure is the main exogenous factor responsible for aging in the skin, especially in fair-skinned Caucasian subjects and exerts its effect predominantly through the accumulation of free radicals in the tegument. Smoking, pollution, sleep deprivation, and poor nutrition are other exogenous factors that promote skin aging. The difference between the two types of skin aging—exogenous and endogenous—can be observed by comparing UV-protected and UV-exposed sites. Endogenously aged skin displays epidermal and dermal atrophy, a reduced extracellular matrix (collagen, elastin fibers, and glycosaminoglicans), and marked vascular changes. Skin functions are impaired: thermoregulation, glandular function, wound healing, the epidermal barrier, and melanogenesis are all diminished. Exogenous aging also displays thickened stratum corneum, the aggregation of abnormal elastic fibers in the dermis (solar elastosis), and deep altered production and distribution of melanin, which leads to uneven pigmentation.

Diet and Skin Aging

The contribution of diet to how skin ages remains largely unclear. While skin scientists know what skin diseases and impairments can occur because of most nutritional deficiencies (e.g., vitamins E and C, carotenoids, and polyunsaturated fatty acids), we miss studies that precisely correlate the signs of aging with qualitative and quantitative nutrient intakes (Draelos, 2013) We do not know to what extent a “good diet”—which is hard to define—or a supplemented diet can contribute to successful skin aging. Cosgrove et al. (2007) evaluated the associations between nutrient intakes and the appearance of aging skin using data from the first National Health and Nutrition Examination Survey conducted in the United States between 1971 and 1974. Clinical dermatological examinations were conducted of 4025 women ages 40–75 years and data were gathered for their dietary habits and other variables (e.g., body mass index, race, energy intake, physical activity, and smoking). The authors found that higher intakes of vitamin C and linoleic acid and lower intakes of fats and carbohydrates were associated with better skin aging appearance (fewer wrinkles, less senile dryness, and less skin atrophy) independently of other factors known to affect skin aging. This study is different from many others in the literature because it examined nutrient intakes from food rather than from nutritional supplements or topically applied nutrients. Nevertheless, no direct conclusion about nutrients and skin aging appearance could be determined. Significant dietary changes have occurred in the past 30 years, however, and the use of facial cosmetics has seen a tremendous increase. For these reasons, studying the relationship between dietary attitudes and skin aging has become even more complicated. On one side is the structural and biochemical complexity of aging in skin and its appendages; on the other side is the extreme variability of genetic, physiological, and pathological factors as well as environment and behavior. All of these affect our knowledge in this field. Until we have at our disposal techniques to make in vivo measurements of the different nutrients in the skin (this can only be considered science fiction now), it will be almost impossible to accurately evaluate the effect of single or grouped dietary constituents on skin aging. Anyway, although science and common sense suggest that a healthy diet such as the Mediterranean diet with its emphasis on fresh fruits and vegetables, nuts, fish, olive oil, and integral cereals may improve aging in general and skin appearance in particular, many challenges remain in designing and running nutritional research (Draelos, 2013). If we look at the aging phenomenon on a biological basis, we may be able to better predict how nutritional factors can affect it. Up to now, the main mechanisms causing aging of tissue and organs are as follows:

ent Oxidative stress

ent Nonenzymatic glycation products

ent Sex hormone imbalance

ent Telomere shortening

In this chapter we will analyze each of these mechanisms and their correlations with dietary habits.

Oxidative Stress and Chronic Inflammation

Reactive oxygen species (ROS) are essential to life. We breathe oxygen, and properly generated ROS has beneficial protective and antiaging effects on cells. Nevertheless, ROS production from several sources in our everyday lives such as UV exposure, inflammation, stress, pollution, and smoking leads to an excess of free radicals that hurt the chemical stability of cellular structures. This is why cells have their own intrinsic antioxidative enzyme systems such as superoxide dismutase that are able to neutralize ROS by taking a free electron from another source. Vitamins A, C, and E and polyphenols all exert strong antioxidation effects and work synergistically. A fundamental strategy for enhancing skin protection from oxidative stress is to support the endogenous antioxidant system via the antioxidants normally present in the skin. Since these antioxidants work in a complex harmony, a permanent intake of isolated antioxidants is not physiologically as effective as consuming a diet rich in fruits and vegetables; this remains the healthiest and safest way to maintain youthful and healthy skin.

A vast literature has been produced over the past decades about the role of antioxidants in a balanced diet. Even more detailed recent studies directly correlate dietary intake of antioxidants with skin protection: resveratrol has been demonstrated to attenuate skin atrophy induced by oxidative damage (Watanabe et al., 2015), and cocoa (Karim et al., 2014) and green tea polyphenols (Roh et al., 2015) confer protective effects on skin against UV-induced acceleration of skin aging. So far, a variety of phytomolecules derived in particular from polyphenols, triterpenes, and sterol classes have demonstrated a promising activity on skin aging. Among them, carnosic acid, curcuglicoside, curcumin, glycyrrizic acid, and extracts and pure compounds from Fabaceae, Asteraceae, and Zingiberaceae appear most interesting (Tundis et al., 2015). In particular, maslinic acid found in olive oil is a natural triterpene that has protective effects against chronic inflammatory diseases through its modulation of arachidonic acid metabolism (Yap and Lim, 2015).

Nonenzymatic Glycation Products

Nonenzymatic glycation was first diagnosed and described in diabetic patients as leading to the accumulation of advanced glycation end (AGE) products in several tissues and organs. AGEs have been associated with end-stage renal disease, chronic obstructive pulmonary disease, atherosclerosis, and connective tissue impairment. The term glycation has emerged in recent years to describe one of the most important aging factors for human tissues and organs (Simm et al., 2015); it now commonly refers to the nonenzymatic process of proteins, lipids, and nucleic acids covalently bonding to the sugar molecules glucose and fructose. Glycation occurs at random molecular sites and generally results in the inhibition of the target molecule’s functions. Immunostaining has demonstrated the presence of glycation in aged skin and resulting structural, morphological, and functional impairments. Glucose and fructose play a critical role in glycation, but foods containing glycated proteins also provide further exogenous AGEs to an organism. Barbecued meats, toasted bread, dark-colored soft drinks, and donuts contain high levels of AGEs. Now we know that grilling, frying, and roasting methods produce higher levels of AGEs in cooked food. Orally consumed and endogenous AGEs are proinflammatory and accumulate on nucleic acids, proteins, and lipids. Fortunately, dietary habits can reduce AGEs in the body. First, a diet should contain low levels of monosaccharides, which are responsible for the glycation phenomenon. Water-based cooking methods such as boiling and streaming produce a logarithmically lower amount of AGEs. Several aromatic herbs and spices are believed to be able to reduce the endogenous production of AGEs: cinnamon, oregano, cloves, ginger, garlic, α-lipoic acid, carnitine, flavonoids, resveratrol, vitamins, zinc, and manganese. Furthermore, since glycation is accelerated in the presence of an ROS, the intake of antioxidants is able to limit the production of endogenous AGEs (Draelos, 2013).

Sex Hormone Imbalances

Some of the changes that affect aging skin in menopausal women occur as a consequence of estrogen deficiency. The mechanisms involved seem to originate from the dermal and epidermal reduction of cellularity, collagen quantity, and skin thinning. This mechanism is responsible for a total cumulative loss of about 30% of skin thickness in the first 5 years after menopause. Keratinocytes and dermal fibroblasts exhibit receptors for sexual hormones, which is why we observe collagen and glycosaminoglycans deficiency after menopause. The role of estrogens in maintaining dermal thickness is demonstrated by the fact that orally administrated isoflavone-rich soy extract during six consecutive months causes significant increases in epithelial and dermal thickness (Accorsi-Neto et al., 2009). Since estrogen therapy is not always feasible due to its side effects and contraindications, phytormones in the diet represent a natural and valid alternative to hormonal therapy after menopause. Although phytoestrogens are nonsteroidal substances, they have a heterocyclic phenolic composition that shows structural similarities to the estrogens. Of particular interest is their higher affinity for the β subtype of the estrogen receptor that is present in bones, skin, and the cardiovascular system (all the organs suffering from estrogen deprivation after menopause) while having reduced or even antagonist effects on the α subtype of the estrogen receptor (found in the uterus and breast, which are at higher risk of cancerization after estrogen stimulation). This is why phytoestrogens are considered selective estrogen receptor modulators and are widely used to treat menopause estrogen deficiency. Soy isoflavones—in particular, genistein—are the best studied phytoestrogens (Nagaraju et al., 2013). Anyway, while soy is very abundant in many Asian diets, it is not characteristic of the Mediterranean diet, which helps explain why not all Western women are able to tolerate it. Also allergies to soy are more frequent in Western countries (Cordle, 2004). Other vegetables contain many other natural sources of phytoestrogens (Agradi et al., 2006). Species belonging to the Leguminosae, Apiaceae, Graminaceae, Iridaceae, Chenopodiaceae, Cruciferae (or Brassicaceae), and Solanaceae families provide significant amounts of phytoestrogens. Among the species from these families are such widely consumed foods such as beans and other legumes, tomatoes, cabbage, carrots, and some cereals. When supported by proper cooking practices as in the Mediterranean tradition, vegetable foods rich in phytoestrogens can help maintain healthy and young skin.

Telomere Shortening

Telomeres are DNA–protein complexes at the end of chromosomes that protect the genetic material and promote chromosomal stability. Telomeres shorten with time because they cannot replicate completely each time the cell divides; for that reason, they may be the most powerful biological clock yet elucidated. Furthermore, it has been demonstrated that being overweight, stressed, and sedentary accelerates the shortening of telomeres (Epel, 2012). Progressive shortening of telomeres leads to senescence, apoptosis, and oncogenic transformation of somatic cells that affect an individual’s health and lifespan. Shorter telomeres have also been associated with increased skin aging (Kosmadaki and Gilchrest, 2004; Masood, 2011).

Telomere length positively correlates with the dietary intake of fiber and negatively associates with waist circumference. A diet rich in antioxidant omega-3 fatty acids and vitamins C and E, and beta-carotene is associated with a reduced rate of telomere shortening. Antioxidants are known to protect telomeric DNA from oxidative damage caused by extrinsic and intrinsic DNA damaging agents. Reduced protein intake also seems to increase cell longevity. Of notable interest is that improved nutrition, increased exercise, and better stress management might also booster the enzyme telomerase, which directs the replication of telomeres and adds telomeric repeat sequences to the chromosomal DNA ends.

The Mediterranean Diet

The Mediterranean diet was studied for the first time in a systematic and scientific way by American scientist Ancel Keys, who demonstrated the influence of diet on longevity and health. This analysis involved some Mediterranean countries in the 1950s following the austere times in the wake of World War II, which were characterized by a physically active lifestyle and a frugal diet based mostly on vegetable products (Monteagudo et al., 2015). The Mediterranean coast is characterized by great ethnic, cultural, religious, economic, and political differences that may have influenced the quantity and quality of food. Nevertheless, these countries traditionally share the availability of the same foods derived from agriculture, herding, and fishing. Some studies widely accepted by the scientific community showed that in the early 1960s in these geographical areas, life expectancy was almost the highest in the world and that the incidence of heart disease, some cancers, and other chronic diseases related to diet was among the lowest in the world. This occurred despite high smoking, low socioeconomic levels, and a shortage of health care. It is significant that this diet is common where olive trees are traditionally grown; one accepted definition of this nutritional pattern relates to diet practiced in Mediterranean areas dominated by olive trees (Keys, 1980).

The characteristics of the Mediterranean diet are abundant fruits, vegetables, wholemeal bread and cereals, legumes, nuts, and seeds, all of them fresh, natural, seasonal, and locally sourced. Olive oil is the principal source of fat, daily servings of fresh fruit are used as dessert, and refined sugars or honey are consumed only a few times a week. Dairy products (principally cheese and yogurt) are consumed daily in moderate amounts, as are fish and poultry. Only a few eggs (0–4) are consumed per week; red meat is eaten in modest amounts; and wine, generally red, is also consumed in modest amounts, generally during the meal (Pitsavos et al., 2005). Numerous studies over several decades confirmed that the Mediterranean diet can reduce the risk of cardiovascular and metabolic disease and improve cognitive health (Davis et al., 2015), but what about skin health?

Recent publications regarding the correlation between eating habits and skin cancer have demonstrated that the Mediterranean diet may contribute to lower rates of skin cancers despite high levels of solar radiation in Mediterranean countries (Fortes et al., 2008; Malagoli et al., 2015; Shapira, 2010). Taking into account what we learned from the scientific literature and what has been explained in this chapter, the correspondence between the Mediterranean diet and good dietary habits based on potentiating antiaging mechanisms in the skin is quite high (Fig. 2.1).

image
Figure 2.1 Skin Mediterranean diet pyramid. Adapted from Dernini, S., Berry, E.M., 2015. Mediterranean diet: from a healthy diet to a sustainable dietary pattern. Front. Nutr. 2: 1 (Dernini and Berry, 2015).

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