Understanding skin aging: Exploring anti-aging modalities

INTRODUCTION

Skin is the first defense against the external environment from physical and chemical stimuli and infective organisms. It has an immaculate power to shed and regenerate in an orderly time-bound fashion. Genetic factors, sun exposure, occupational activities, and time – all contribute to the aging process of the skin. Although aging changes also occur in other organs/systems of the body, the skin shows visible signs of aging to one and all. As the expectancy of life has increased throughout the world, we are encountering an increasing number of aging populations desperately seeking advice to delay or reverse the signs of aging. The present communication attempts to address these important aspects of both causes and remedies of this natural process.

THEORIES OF AGING

There are two basic theories of aging that have been put forward to explain the complexity beneath – Programmatic theory and Stochastic theory.

The programmatic theory is comprised of telomere shortening and cellular senescence. As the age advances, the human telomere shortens over 30%. Telomeres of patients with premature aging syndromes such as progeria are significantly shorter than their age-matched controls. Cellular senescence denotes a limited capacity of cells to undergo cell division leading to altered differentiation, irreversible growth arrests, and resistance to apoptosis.^[1,2] The stochastic theory postulates that a four-pronged process operates in the aging skin [Table 1].

EXTRINSIC SKIN CHANGES

As age advances, the tell-tale signs of aging start to display on the body gradually, which may vary from individual-to-individual, geographic areas, race, and occupation involving excessive sun exposure, etc. Face, hands, and feet are the first to show chronologic aging and photoaging.^[3] Atrophy, wrinkling, laxity, sagging, pigmented blemishes, and dryness can be seen on the skin along with greying of the hairs. With time, they become more pronounced and disturbing; pigmentary changes also develop in sun-exposed areas. The liver spots, senile lentigo, and seborrheic keratoses keep developing and increase in number with time. Hair becomes grey, density may reduce, and the anagen phase of hair follicles progressively shortens. Paradoxically, eyebrows can become bushy in the elderly. In aging females, hirsutism may be a cause of concern – grey terminal hair on the chin even resists the hair removal lasers. Previously full face gives a look of weakening, wrinkling, and reduced facial musculature. The neck shows non-elastic wrinkled sagging skin. The nails may become lusterless and show thickening and longitudinal ridging [Figure 1]. The dry skin of the elderly is a continuous source of irritation and pruritus. Senile people, thus, become prone to xerotic skin conditions like asteatotic dermatitis. Pressure sores can develop over the skin of the pelvis due to loss of subcutaneous fat.^[4]

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Figure 1:

Extrinsic skin changes seen in the mother (left) compared to her daughter (right).

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INTRINSIC SKIN CHANGES

ANTI-AGING MODALITIES

The scientific, in depth knowledge of the sophisticated aging and photoaging processes has led us to rational research, both for preventing and delaying the process of aging. Several approaches have been advocated to reverse the aging process to some extent. Everyday, new pharmacological, noninvasive, and laser/surgical intervention is being added to the ever-expanding basket of anti-aging therapy. It is worthwhile to briefly recount them [Figure 2].

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Figure 2:

Broad classification of anti-aging modalities.

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PHARMACOLOGICAL AGENTS

Both oral and topical pharmacologic agents have been advocated for preventing, tackling, and delaying natural photoaging. It is believed that the prevention, especially that of ultraviolet radiation exposure from early childhood can go a long way in reducing extrinsic skin aging. Wearing protective clothing and using physical and chemical sunscreens, along with avoidance of sunlight, form a substantial denominator of any anti-aging treatment.

CHEMICAL PEELS

Another substantial therapy widely used for age diminishing is different varieties of chemical peels. They have shown promising results when used either alone or with combination of different agents [Table 6].^[51,52]

ENERGY-BASED DEVICES

A selective heat-induced denaturalization of dermal collagen which results in subsequent reactive synthesis is the principle behind various types of light devices. Laser, intense pulsed light, and radiofrequency can be effectively employed for rejuvenation, resurfacing, and tightening of the skin. Laser resurfacing has been shown to be very encouraging in reversing the photoaging by causing extensive dermal remodeling, regeneration of cellular organelles, and stimulation of neocollagenesis.^[53-55]

DERMAL FILLERS AND INJECTABLE SKIN REJUVENATORS

Dermal fillers can be injected within or beneath the skin to improve the blemishes and to cause soft tissue augmentation. They very useful in treating permanent wrinkles like crow’s feet and prominent nasal labial furrows^[27,56] [Table 7].

BOTULINUM TOXIN AND PLATELET-RICH PLASMA (PRP)

Although it has an insignificant effect on skin aging or skin texture on a molecular level, the botulinum toxin is often prescribed for slowing down the visible aging process by acting on dynamic wrinkles.^[57] It is used in various dilutions at various sites and repeated after variable intervals of several months. PRP derived from fresh whole blood of the subject has a very high concentration of platelets which harbor various growth factors including platelet-derived growth factors, transforming growth factors, vascular endothelial growth factors, and insulin-like growth factors. All these growth factors are known to regulate processes including cell migration, attachment, proliferation, and differentiation; promoting ECM accumulation by binding to specific cell surface receptors. This in turn induces the synthesis of collagen and other matrix components by stimulating the activation of fibroblasts, resulting in skin rejuvenation.^[27,58]

ANTI-AGING DIET

Calorie restriction has remained a longstanding advice that delays age-associated diseases and extends the lifespan of an individual. Time and again, claims of intermittent fasting, ketogenic diet, protein restriction, time-restricted feeding, diet restriction of certain amino acids, and fast-mimicking diets have been advocated in natural anti-aging regimens. Although the effects seem to be highly variable and inconsistent, some anti-oxidant properties of such diets causing the elimination of reactive oxygen species may be beneficial to some extent.^[59]

HORMONE REPLACEMENT THERAPY (HRT)

The progressive decrease of hormone synthesis with age makes it logical to use HRT in select individuals – both males and females, with overall benefit in the quality of life and halting signs of aging.^[27,60] Melatonin is one such example, other being estrogen and progesterone. Obese men with Type-2 diabetes mellitus have a low testosterone level and can be advised a controlled testosterone therapy, improving their stamina as well as skin tone.^[61]

CONCLUSION

With increasing longevity, improved comforts, better standard of living, and abundant social interactions, the humankind is getting more concerned about their physical appearance and youthful personality. The first blemish on the face or a fine line on the forehead can be a significant cause for concern for any self-conscious socialite person. Understanding the aging mechanism has translated into a plethora of modalities available for preventing and delaying aging. Social media has also increased awareness about the use of beautifying creams promising a glowing, youthful skin. Thus, an ever-increasing number of people approach skin specialists for various procedures and cosmeceuticals to prevent their skin from signs of senescence. Sunscreen common to all age-defying agents can also be used prophylactically to prevent photoaging, the spectrum of which has now included visible light, infrared rays, and anti-pollutants. The future is getting more and more promising in the field of senescence and skin rejuvenation. An accurate understanding of the aging process up to genomic levels has made it possible to identify novel targets for better prevention, maintenance, and reduction of chronological aging and photoaging.