Dr. Shahrzad Alimohammadi, PharmD, PhD Candidate
Table of Contents
Introduction
Skin is one of the most complicated organs in the human body when it comes to structure and function. It serves as a physical barrier, prevents electrolyte and water loss, regulates body temperature, and aids the immune system in fighting pathogens. There are several receptors, such as autonomic and sensory receptors, that respond to various exogenous stimuli including vibration, touch, temperature, pressure, itch, and pain.
There are 3 main layers in the skin named epidermis, dermis, and hypodermis, from the outermost to the innermost, respectively, and each is divided into several other layers themselves (Fig. 1 and 2). The condition of the skin reflects very much on one’s general state of health and is relatively malleable. This article will summarize ways in which the reader can keep their skin healthy as they age.
What Happens to the Skin with Aging?
Aging is mainly characterized by intrinsic (chronologic) and extrinsic processes. Chronologic aging is considered genetically driven, a process that is irresistible and followed by laxity and exaggerating expression lines (Khavkin and Ellis 2011). In addition, a combination of factors such as ultraviolet (UV) radiation, high alcohol consumption, tobacco, low body mass index (BMI), air pollution, and lower socioeconomic status contribute to skin aging (Goodman et al., 2019).
Skin aging is a natural process that presents as laxity, wrinkling, and pigmentation changes (Khavkin and Ellis 2011). Wrinkles (rhytids) develop at fault lines in aged skin. Although the mechanisms differ, the lines are a consequence of facial expressions and possibly skin deformity caused by mechanical compression during sleep. Shear, stress forces, and compression affect the face in lateral or prone sleep positions (Anson et al. 2016).
Flattening of the dermal-epidermal junction leads to a thinner epidermis. Surface area loss of dermal-epidermal interface results in higher fragility and lowered transfer of nutrients through dermis and epidermis. Slower wound healing, as well as less functional desquamation, happens due to a decreased epidermal cell turnover. Changes lead to skin atrophy, reduced fibroblasts, and subdermal adipose tissue. Collagen fiber bundles reduce with age and lead to a decreased collagen type III/I ratio.
External factors, in particular sun exposure, contribute to extrinsic aging. Photoaging manifests as rhytids, dryness, irregular pigmentation, telangiectasias, loss of elasticity, and purpura. Histological features of aged skin include elastin accumulation below the dermal-epidermal junction or elastosis in addition to epidermal atrophy, collagen, and elastic fibers fragmentation (Khavkin and Ellis 2011).

Fig 1. The 3 layers of the skin: epidermis, dermis, and hypodermis (Wikimedia)

Fig. 2: Layers of the epidermis (hematoxylin-eosin 10x) (Wikimedia)
Factors that Contribute to Aging of the Skin
We might not be able to stop the clock on the aging of our skin, but we can influence the velocity of the change. Below are seven factors that contribute to skin health. Knowledge of these factors can help you maintain healthy and glowing skin well into your older years.
1. Diet and Hydration
Diet is a critical player in the treatment and prevention of many diseases, including
dermatological disorders. Acne, skin cancer (e.g., NMSC), skin aging, and psoriasis are
examples of skin diseases that might benefit from a rich and healthy diet (Rezaković et al.,
2014). If you have a skin disorder, it is a good idea to take a closer look at your diet and
determine which foods may be playing a role. Lifestyle and dietary modifications can help
improve many skin disorders manifestations and their severity, namely acne,
psoriasis, and even the aging process (Katta and Desai 2014).
Inflammatory skin diseases such as atopic dermatitis (AD), acne vulgaris (AV), and psoriasis benefit from a healthy and nutrient-rich diet. Healthy foods may decrease skin findings and reduce
inflammation. The goal is to follow a lower glycemic index (GI) by avoiding bread, rice,
pasta, and cereal and using acids such as lemon juice or vinegar to lower AGEs to 50%
(Prussick 2019). To conclude, diet and food intake are involved in preventing several
diseases such as systemic and dermatological disorders and impacting one’s
health. Here is an article with more information on healthy carbohydrate options and dietary suggestions.
Hydration status is important not only to maintain good skin health but for general health. The skin contains about 30% water and is a barrier to water loss. It is, however, semi-permeable, with water exiting through the sweat glands. Outdoor exposure to high-intensity sunlight can accelerate dehydration. Hydration maintains thermoregulation, organ function, proper vascular mechanics, and healing. Some studies have shown improvement in wound healing when hydration status is optimal. Contrary to popular opinion, adequate hydration will not ward off wrinkles.

Fig. 4: Food can effect level of blood sugar and consequently impact the skin
2. Exercise
Exercise is beneficial for skin health and can reduce the changes of aging.
According to the literature, impaired mitochondrial metabolism results in the changes seen in aging skin.
Based on a paper published by Crane et al., exercising regulated the expression of IL-15 via
skeletal muscle AMP-activated protein kinase (AMPK). Muscle AMPK eradication leads to
skin degeneration thus low doses of IL-15 treatment might be a favourable option to diminish
skin aging besides improving wound healing (Crane et al. 2015; Wong et al. 2019).
Additionally, advanced glycation end-products (AGEs) increase with aging and are involved in
metabolic disorders and tissue modifications. Hence, long-term exercise reduces
glycation and improves Achilles tendon size, preventing injury (Hjerrild et al. 2019).
Facial skin aging is linked to weakened and depleted mimetic muscles. Therefore, one practical tactic is resistance training of facial mimetic muscles to tackle skin aging. Kyunghee
facial resistance program (KFRP) results in a more firm and elastic skin and represents a positive role in facial and neck skin elasticity and mechanical properties. This exercise
program is isometric and includes five resistant movements using fingers (Kim et al. 2016).
Continued exercise training affects the skin blood flow in response to exercise, along with
cutaneous microvascular reactivity changes (Simmons et al., 2011).
3. Sleep
Skin sleep wrinkles occur due to sleep position and site of superficial muscular aponeurotic
system (SMAS) condensation. Sleeping on the side or prone will put facial tissues at the
risk of tensile, shear, and compression mechanical forces (Fig. 6). Sleeping duration and
position significantly affect these forces and their consequences. Supine (back) sleeping is
recommended, even though we unconsciously change our position during our sleep, and it might
take a long time (4 weeks) to adjust to changes in sleeping routines (Anson et al., 2016).
Based on another study, persistent poor-quality sleep increases the signs of diminished skin
barrier function, intrinsic aging, and lower appearance satisfaction. In addition, poor sleepers have
higher levels of uneven pigmentation, fine wrinkling, skin laxity, benign skin growth, and
loss of subcutaneous fat compared to good sleepers. Therefore, good sleep quality aids skin recovery
from UV-induced erythema and improves the self-perception of general appearance.
Acute sleep deprivation and stress are possible factors in damaging the integrity of human skin.
Decreased skin barrier function recovery is an outcome of acute sleep loss. Moreover, the risk
of obesity is higher in chronic sleep deficiency (Oyetakin-White et al. 2015).
As it has been stated in the literature, sleep disorders may be associated with dermatological disorders, including eczema, psoriasis, and skin cancer (Walia and Mehra 2016).

Common expression wrinkles.
4. Substance Use: Smoking and Alcohol
Smoking and alcohol consumption are well-documented to affect the skin and prematurely age the skin. Smoking is associated with cutaneous microvascular constriction. This is
induced by the amount and duration of the exposure to smoking. Alcohol consumption impacts the skin’s antioxidant defense system as it decreases carotenoid concentrations in the dermis. Alcohol also leads to peripheral vasodilation that results in facial capillaries becoming dilated. Under-eye puffiness, wrinkles, uneven skin tone, as well as
losing volume under the eyes, lips, and midface are possible manifestations of age (Goodman
et al. 2019).
Several subtypes of the nicotinic class of acetylcholine receptors, such as the α7 receptor, are
present and expressed on all skin cell types.
Neither wrinkles nor colors disappear when the lesion is stretched. The longer the habit, the higher the
degree. Cessation of the habit, especially if it is not of long duration, eventuates in
the disappearance of the lesion (Ortiz and Grando 2012).
5. Skin injury and sunburn
UV radiation can be both beneficial and harmful to the human skin. UV exposure results in
immunosuppression, sunburn, carcinogenesis, and skin aging. Thus, photoprotection is highly
recommended.
UV radiation may also assist in the diagnosis and treatment of many skin disorders. Photobiology is mainly focused on the UV spectrum, which can be both
therapeutic and harmful in dermatology. UV can harm the skin via sunburn,
UV-induced skin cancers, and premature skin aging. It also plays a role in cutaneous disease
treatment, including atopic dermatitis (AD), T-cell lymphoma, psoriasis, and
diagnosis of several other diseases.
Generally, short-wavelength light is used to treat epidermal diseases, and long-wavelength light targets deeper layers, for instance, thicker lesions and even sebaceous glands. UV light is subdivided into 4 types based on their
wavelength ranges, such as UVC (200-280 nm), UVB (280-320 nm), UVA2 (320-340 nm),
and UVA1 (340-400 nm). UVA can penetrate the deep dermis, and UVB is absorbed in the
epidermal layer. The area of the electromagnetic spectrum which has the highest impact on
cutaneous health and disease is called UVR.
Thus, post-UVR exposure acute changes like tanning, sunburn, epidermal hyperplasia, proinflammatory and immunosuppressive modifications, and synthesis of vitamin D. Besides, other chronic changes may manifest upon UV radiation such as photoaging and photocarcinogenesis. As such, photoprotection is crucial in UVR exposure. Various skin disorders, including AD, psoriasis, cutaneous T-cell lymphoma (CTCL), scleroderma, vitiligo, facial rejuvenation, and acne (Christensen et al., 2017).
6. Anti-aging topical skin treatments
UV radiation plays a crucial role in skin sunburn and might also lead to harmful
products that develop skin aging through reactive oxygen species (ROS). Several pharmaceutical
dosage forms, for instance, creams supplemented with antioxidants, prevent the unwanted outcomes of
UV exposure by ROS quench. Herbal creams consisting of Phytoextracts fight against UV exposure
injuries.
Some examples of these herbals are Acacia nilotica, Benincasa hispida, Calendula
officinalis, Camellia sinensis, Camellia sinensis, Nelumbo nucifera, Capparis decidua, Castanea
sativa, Coffea arabica, Crocus sativus, Emblica officinalis Gaertn, Foeniculum vulgare, Hippophae
rhamnoides, Lithospermum erythrorhizon, Malus domestica, Matricaria chamomilla L., Moringa
oleifera, Morus alba, Ocimum basilicum, Oryza sativa, Polygonum minus, Punica granatum, Silybum
marianum, Tagetes erecta Linn., Terminalia chebula, Trigonella foenumgraecum, and Vitis
vinifera.
In addition, flavonoids and phenolic acids play a role in skin protection against UV-induced damage. Although, more research and studies are required to confirm their anti-aging effects (Jadoon et al., 2015). Several other supplements, both internal and topical, help as anti-aging compounds, including
curcumin, epigallocatechin gallate (EGCG) content in the green tea, collagen, CoQ10,
Crocin, theanine, Rhodiola, garlic, astragalus, fisetin, resveratrol (Kubala and Seitz 2020) .
7. Skin and the microbiome
The role of the skin microbiome in skin aging has been well-documented in the literature. The skin has a variety of microenvironments for bacteria, depending on the pH, gender, moisture, temperature, and products secreted in specialized areas of the skin. Extrinsic factors include clothing worn, creams applied, cosmetics, and antibiotics. Changes associated with aging shift the microbiome of the skin. For instance, adolescent changes in sebum production lead to the colonization of the yeast Malassezia.
Several predominating microbial communities exist on the skin, including, i.e., Cyanobacteria, Staphylococcus, Cutibacterium (formerly Propionibacterium acnes), Lactobacillus, Corynebacterium, Streptococcus, Neisseria, Candida, and Malassezia. Interestingly, the condition of the microbiome of the skin and gut may impact the process of aging in the skin. A greater understanding of the microbiome will allow a more predictive assessment of the status of human health. Other factors that affect skin aging include resistance to UV radiation, immune response modifications, metabolism, and the biosynthesis of substances related to age (Li et al. 2020).
Summary
Skin changes with aging are variable and modifiable to some extent. The human body interacts on all levels, the skin being the tip of the iceberg. When care is taken with lifestyle choices, including diet, exercise, sleep, stress, it can have benefits on the health of your skin.

Shahrzad Alimohammadi is a Pharm.D. and currently a junior research fellow at the Department
of Immunology, University of Debrecen. She is a Ph.D. candidate, and her research mainly
focuses on the skin’s immune cells, including Langerhans cells and dendritic cells and their
possible roles in the skin!
Pharmaceutical technology, as well as dermatology, are her favorite topics when it comes to
research. In the dermatological field, Shahrzad is interested in inflammatory and immune-related
skin diseases and cosmetic dermatology.
References
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