Skin ailments and concerns can be best addressed when underlying cellular functions and processes are understood. Cellular metabolism at the mitochondrial level can tell us much about how skin changes throughout time and when exposed to different conditions, as well as what is affecting our skin and its appearance. Currently, the skin care industry is engaged in research to determine the best ways to harness mitochondrial functions for use in the fight against premature aging and skin cancer, among other concerns.
Known as the “powerhouses” of cells, the main function of our oval-shaped mitochondria is cellular respiration (oxidative metabolism or oxidative phosphorylation), during which the mitochondria generate energy for the cell as a whole by processing the nutrients we ingest into charged molecules, ultimately producing adenosine triphosphate (ATP) molecules, which provide energy for most energy-consuming activities within the cell. If you think of the human body as the cell, your intestines are the mitochondria; when you ingest food, the intestines break it down for energy, and when a cell “ingests,” its mitochondria are responsible for breaking down the components for energy in the same way.
Mitochondria have two membranes made of phospholipids and proteins: a smooth outer membrane and a highly folded inner membrane. The outer membrane of mitochondria is semi-permeable, allowing only small molecules and ions to come in and out. The inner membrane is permeable to oxygen, carbon dioxide and water, and is folded many times over; these folds are known as cristae, which encompass more surface area in order for chemical reactions to take place. Molecules and enzymes that create ATP reside on and within the folds of the cristae. The space between the outer and inner membranes is the intermembrane space, which is made up of the gel-like matrix; this matrix consists of a fluid that contains a mixture of water and proteins. The enzymes that catalyze the reactions of respiration (ATP) are components of both the gel-like matrix and the inner mitochondrial membrane.
The gel-like matrix space contains mitochondrion-specific DNA (mtDNA), ribonucleic acid (RNA) and ribosomes that participate in the synthesis of several mitochondrial components. Besides cellular respiration and fatty acid oxidation, mitochondrial functions also include thermogenesis (heat production), hypoxia (oxygen reduction) management and triggering of apoptosis (cell death), all via complex enzymatic mechanisms.
This process is error-prone and ultimately leads to the generation of reactive oxygen species (ROS), which are highly active free radicals, making the mitochondria the site of highest ROS turnover in the cell, and exposing nuclear and mtDNA to oxidative damage. The repair mechanisms available for mtDNA are limited and the mutational rate of mtDNA is approximately 50 times higher compared to nuclear DNA. Mutations of mtDNA may play a major causative role in the normal aging process with the accumulation of mtDNA mutations accompanied by a decline in mitochondrial functions.
Accumulation of random oxidative damage caused by ROS mutations of DNA lead to what we consider characteristic signs of aging, including the development of fine lines and wrinkles, decreased or impaired barrier function, and loss of skin tissue. These macro aspects are direct consequences of loss of enzymatic activity, the specific signaling cascade that leads to increased known as matrix metalloproteinase-1 (MMP-1), or interstitial collagenase, expression and consequent collagen degradation. The damaged proteins accumulate within the mitochondria while oxidative phosphorylation decreases and synthesis of ATP molecules becomes impaired, which causes further physiological failures.
The occurrence of apoptosis as a result of mitochondrial dysfunction has been linked to organ malfunction, skin diseases, cancer and aging. The epidermal keratinocytes in the skin when exposed to ultraviolet (UV) radiation have been found to be particularly sensitive to the decline of mitochondrial function and mtDNA mutations, making them potential markers of photoaging. The so-called “common deletion” of mtDNA is increased up to ten-fold in photoaged skin compared to sun-protected skin of the same individuals.1 It has been shown that two weeks of sun exposure (in particular UVA radiation) leads to an approximate 40 percent increase in the levels of “common deletion” in the dermis, which persists for at least 16 months;2 the defective respiratory chain then triggers further damaging cascades independent from the primary inducing agent.
Due to the prominent role of mitochondria in both intrinsic and extrinsic aging, the skin care industry is actively looking into the many ways mitochondria might play a role in skin health and anti-aging specifically. Protecting mitochondria from UV-induced damage, in particular UVA-generated mtDNA mutations, is an important step that can be achieved by using broad spectrum UVA/UVB sunscreens and applying recommended sun protection measures.3 Anthocyanins and some other plant pigments have also been shown to exhibit UV-protective effects on human skin cells, representing a useful addition to mitochondria- protecting regimens.
In terms of fighting signs of aging by targeting skin cells and the mitochondria specifically, topically applied antioxidants are effective in preventing mitochondria-induced MMP-1 expression and consequent deterioration of the extracellular matrix. Antioxidants are molecules capable of scavenging reactive oxygen species through several mechanisms. The most documented as having potent antioxidative properties and most widely used for skin care and skin protection purposes include L-ascorbic acid, tocopherol and polyphenols (resveratrol, silymarin, green tea extract and grape seed extract, to name a few).
Niacinamide is a coenzyme precursor for important redox coenzymes – nicotinamide adenine dinucleotide (NAD+), nicotinamide adenine dinucleotide phosphate (NADP+) – and their reduced forms, NADH and NADPH, respectively, which play important roles in many enzymatic reactions, allowing for an exceptionally broad spectrum of effects that topical niacinamide exhibits on skin. Among those multiple effects, niacinamide has been shown to decrease ROS production by mitochondria and to extend the replicative lifespan of fibroblasts,4 an effect that points to the boosting of mitochondrial function and the protection of mitochon-
drial genome.
Coenzyme Q 10 is another ingredient that has been shown to improve mitochondrial function and efficacy, as well as to perform as an antioxidant.
If active ingredients can be designed to stimulate aconitase enzyme activity in mitochondria to prevent the ever-increasing damage from cellular oxidative stress, beneficial anti-aging possibilities for personal skin care are conceivable. Aconitase is a crucial enzyme in the citric acid cycle that is specifically altered by oxidative damage, resulting in a loss of catalytic functions and, consequently, to a decline of mitochondrial function.
Given the significant role mitochondria and their metabolism play in the aging process, it is not surprising that the skin care industry is focusing significant efforts on developing products which will protect mitochondria and boost their function. Such products will contribute to increased skin cell protection, longer cellular life, improved barrier function and a better functioning extra- cellular matrix.
Citations:
[1] Koch H., Wittern KP, Bergemann J., J Invest. Dermatol, 2001, 117; 892-7.
[2] Berneburg M., Plettenberg H., Medve-Konig K., Pfahlberg A., Gerls-Barlag H., Geffeler O., Krutmann J., J Invest. Dermatol, 2004, 122; 1277-83.
[3] FDA 2011
[4] Kang HT, Hwang ES, Aging Cell, 2008, 8, 426-38; Matts PJ, Oblong JE, Bisset DL. A, Int. Fed. Soc. Cosmet. Chem. Mag., 2002, 285-9.
Resources:
http://www.buzzle.com/articles/mitochondria-structure-and-functions.html
http://onlinelibrary.wiley.com/doi/10.1111/j.1473-2165.2010.00496.x/pdf
http://www.biology4kids.com/files/cell_mito.html
http://etap.org/demo/biology1/instruction7tutor.html
Prahl S et al., Biofactors, 2008, 245-55.
Voet & Voet, Biochemistry, John Willey & Sons, Inc. 1995
Elsner P et al, JDDG, 2011, 9, Suppl 3 S1-S32
Ivana Veljkovic, Ph.D., manages product development, regulatory and clinical trials for PCA skin®. She received her doctorate in organic chemistry from Freie Universität Berlin, and her master’s of science degree in chemistry from the University of Belgrade in Yugoslavia. Veljkovic has previously worked as a research scientist specializing in the synthesis and purification of organic compounds before joining a health care company in Canada that represented PCA skin®. In her role, she worked directly with physicians, nurses and aestheticians, educating them about skin physiology, ingredients and proper treatments for specific skin conditions.
