Human stem cell proteins: tools to fight the negative effects of aging skin

David L Stachura and Kristen F Rueb

What is aging?

In simple terms, aging is the process of growing old. All organisms, including humans, age over time. All of our organ systems are constantly getting older and reducing their physiological function. This process is almost imperceptible on a daily basis, but it is always occurring. There are multiple hallmarks of aging, such as cell death coupled with an inability of stem cells to replace those that are dying [1]. Cells don’t communicate with each other as well; their ability to promote normal tissue homeostasis becomes altered [1]. Additionally, many believe that the underpinnings of aging is due to low-grade molecular inflammation and oxidative stress [2]. Inflammation and stress are normal events in our body, but as we age, our bodies don’t handle them as well, which leads to age-related diseases such as atherosclerosis, arthritis, cancer, diabetes, osteoporosis, dementia, vascular diseases, obesity and metabolic syndrome [3].

Basically, aging comes down to two main factors: there is intrinsic and extrinsic damage done to our bodies over time. The intrinsic factors are things that we have little control over- they are genetic. Cells have a finite lifespan, and when they die, there is a loss of homeostasis in tissue. Cells can no longer “talk” to each other, secrete extracellular matrix (ECM) proteins, or repair cellular damage as efficiently as they did when they were younger. Decreases in our metabolism and hormonal signaling ensure that aging tissues aren’t going to function as well as they once did. The other factors that affect aging are extrinsic, which we have more control over. They involve our diet, levels of exercise and stress, and exposure to pollutants and other environmental factors. Together, these intrinsic and extrinsic forces play a huge role in aging.

What’s special about aging skin?

Intrinsic and extrinsic forces of aging also affect our skin. Skin is the largest organ system in our body and it has numerous essential physiological functions. Skin protects us against microbes and the environment, helps us regulate body temperature and internal hydration, is a critical part of our immune system, and is necessary for sensory functions. Aging skin obviously loses elasticity and becomes more wrinkled, but that is just a small, visible part of what is going on. Your skin is composed of three stratified layers; there is the outer epidermis, the middle layer of dermis, and the deepest layer, the hypodermis, which is comprised of subcutaneous fat. As our skin ages, all of these layers thin considerably and lose essential functions (Figure 1) [4,5]. In the epidermis, keratinocytes, the most common skin cell, start to change shape and are not replaced as quickly [4]. Active melanocytes, the cells that give our skin color and protect us from ultraviolet radiation, start to decline, giving aging skin uneven pigmentation [6]. And although the number of sweat glands doesn’t decrease, older skin secretes less sebum, which reduces skin moisturizing and antioxidant activity [7]. Moving down to the dermis, aging causes a decrease in cellularity and in vascularity, so blood flow and immune cells are reduced [4,5]. This aging of the dermis results in less glycosaminoglycan production [8], which is important for

Figure 1: Skin thins and is less functional as it ages. Epidermis (top layer), dermis (middle layer), and hypodermis (bottom fatty layer) of skin in young (left) and older skin (right). All layers thin over time, sweat glands secrete less sebum, the tissue is less vascularized, and the number of ADMSCs (blue cells) are reduced (image by Kristine Cordy).

the support of collagen and elastin, important ECM proteins that keep skin tight and youthful. Not surprisingly, these essential ECM proteins are also reduced in aging skin [9], in addition to there being less hyaluronic acid secreted from fibroblasts [8]. Finally, the subcutaneous fat layers in skin diminish significantly, which is important because that’s where adipose derived mesenchymal stem cells (ADMSCs) reside [10], which are essential for tissue homeostasis. Throughout aging skin there is an increase in reactive oxygen species (ROS), which are by-products of cellular metabolism [4,5,11,12]. In younger skin, ROS are processed by the body and rendered harmless, while in aging skin these molecules cause damage to cells and proteins. Most extrinsic factors that have a role in aging seem to do so by causing oxidative stress. Exposure to UV light, which is prevalent especially on the face, hands, neck, and arms accelerates this process, as does exposure to environmental pollutants and lifestyle choices. Importantly, skin is affected by diet, exercise, and stress [reviewed in 13,14]. Overall, the intrinsic and extrinsic forces work hand-in-hand; skin cells and proteins work less efficiently at handling normal tissue homeostasis as they age, and this process is exacerbated by outside forces acting on the skin.

In essence, skin is a unique organ system. It’s exposed to the elements, so it gets barraged constantly by the outside world, especially UV radiation, which causes severe damage to our DNA and proteins on a daily basis. And, it’s the most visible of all our organs, so it indicates an outward appearance of aging to others.

Why do stem cell products uniquely help ameliorate aging?

Sadly, aging is a fact of life. While the appearance of our skin is important, it is also essential for our health and well being. How can we promote healthy skin and fight aging? There are lots of products and procedures promoted that are “anti-aging.” Unfortunately, most products simply address aesthetic issues, and these treatments do very little to actually address aging, which is why they are temporary and lose efficacy over time. There are several treatments for skin aging that address the underlying physiological changes that occur in older skin, such as retinoid treatment and hormone replacement therapy (for postmenopausal women). Another promising treatment is using stem cells and the proteins that they secrete to treat aging.

What are stem cells? Briefly, they are unique cells that live in our bodies that replenish dying mature cells. Every organ has stem cells responsible for it’s replenishment in adults, and skin is no different; over 30,000 skin cells are produced every minute. While there is a population of stem cells that regenerate in the skin’s epidermis [15], the main stem cells present in skin, ADMSCs, reside in the hypodermis [10]. Research shows that these ADMSCs can differentiate into epidermal stem cells [16], indicating that they are likely the most important stem cell population for skin. Sadly, as you grow older, ADMSCs are also susceptible to the intrinsic and extrinsic forces of aging; ADMSCs die off and aren’t replaced as quickly in older skin [reviewed in 17]. Research also shows that these older stem cells lose their ability to secrete proteins and antioxidants, allowing ECM to break down and ROS to further damage tissue. This is unfortunate, because healthy surviving ADMSCs contribute to regeneration of skin during aging [18,19]. ADMSCs secrete ECM proteins like collagen and elastin that reduce fine lines and wrinkles [20] as well as signaling molecules that instruct cells to grow and home to a site of injury [reviewed in 21]. Proteins produced by these stem cells can remodel scar tissue, increase blood flow, and modulate the immune system [22]. Additionally, they block ROS activity by secreting antioxidants [18,19]. There have been transplantation studies that indicate young ADMSCs effectively rejuvenate aging skin [23,24], and ADMSCs secrete a multitude of growth factors that promote cellular homeostasis and repair [25]. Excitingly, you don’t need to actually inject the ADMSCs into your skin to get anti-aging results- the cells secrete proteins into the extracellular space to exert all these actions. Numerous studies show that just using the proteins secreted from ADMSCs helps with a multitude of skin issues, including reducing the appearance of aging [18–25].

Unfortunately, there is no preventing the aging process. Our bodies are not meant to last forever; even the stem cells that keep our bodies functioning eventually start to lose their efficacy. While the molecular underpinnings of aging are somewhat enigmatic, there are ways to counteract the intrinsic and extrinsic factors that affect aging. Human stem cells and secreted stem cell proteins have shown proven efficacy to do just that, with little to no discernible side effects, unlike some other anti-aging treatments like hormone-replacement therapy. The amount of products on the market to “fight” aging is staggering. However, they don’t really address the fact that your skin is changing physiologically and needs to be supplemented instead of just made to look more aesthetically pleasing. The main benefit to using human stem cell-derived products is that they really repair the damage caused by aging in a meaningful way to effectively make your skin look more youthful and healthy.

Works Cited

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