An Anti-Wrinkle Diet: Nutritional Strategies to Combat Oxidation, Inflammation and Glycation

Rajani Katta, MD; Ariadna Perez Sanchez, MD; Evelyne Tantry

Disclosures

Skin Therapy Letter. 2020;25(2):3-7. 

In This Article

The Pathophysiology of Skin Aging

Skin aging is a highly complex process. Our current understanding of this process, while not complete, has indicated that the intricate and intertwined processes of oxidation, inflammation, and glycation play major roles. Each of these is highly impacted by diet.

Ultraviolet radiation (UVR) is the major contributor to extrinsic skin aging, and the impact of UVR on the skin has been well described. UVR is responsible for multiple direct effects on the skin, as well as numerous downstream effects. UVR may produce direct DNA damage via induction of DNA photoproducts.[7] It also results in oxidative stress, with a resultant increase in free radical production, especially reactive oxygen species (ROS).[8] These cause additional DNA damage[9] as well as damage to both structural (collagen and elastin) and enzymatic proteins. Effects on lipids include peroxidation of cell membrane lipids.[10]

Metabolic processes, pollution, smoking, and other factors also contribute to oxidative stress. Due to constant exposure, the body's defense mechanisms are designed to withstand the damaging effects of free radicals. Endogenous enzyme systems include superoxide dismutase, glutathione peroxidase, catalase, and others. The epidermis and dermis also contain antioxidant defenses, including vitamin C, vitamin E, carotenoids, selenium, and others.[11,12] While these are important components of the body's endogenous defense systems, they require constant replenishment from dietary sources. and others. The epidermis and dermis also contain antioxidant defenses, including vitamin C, vitamin E, carotenoids, selenium, and others.[11,12] While these are important components of the body's endogenous defense systems, they require constant replenishment from dietary sources.

Photooxidative stress also activates several inflammatory pathways and contributes to chronic inflammation, which impacts the clinical and molecular features of aging[13,14] as well as the promotion of skin tumorigenesis.[15] Activation of these pathways ultimately acts to increase the expression of several matrix metalloproteinases (MMPs).[13,14,16]

MMPs encompass a number of different enzymes, including collagenases. Along with elastases, these act to remodel the extracellular matrix (ECM), with resulting fragmentation of the collagen and elastin fibers that provide structural support and elasticity to the skin. UVR also results in the reduced expression of tissue inhibitor of MMPs (TIMPs), which ordinarily would act to inhibit ECM destruction.[17]

Several other inflammatory pathways are activated by oxidative stress, including pathways which promote the release of a number of inflammatory cytokines and prostaglandins. The induction of pro-inflammatory genes leads to the release of inflammatory mediators from keratinocytes, fibroblasts, white blood cells, and others, including interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha. These further contribute to the effects of chronic inflammation.

Glycation is another factor that accelerates aging of the skin. Glycation is distinct from photoaging, but is closely intertwined. Glycation refers to the non-enzymatic process whereby sugar molecules covalently bond to proteins, lipids, or nucleic acids. The resulting products are known as advanced glycation end products (AGEs) or glycotoxins. AGEs are a heterogeneous group of molecules, with the prevalent AGE in the human body, including the skin, being carboxymethyl lysine (CML).

Glycation is an important factor in atherosclerosis,[18] renal disease,[19] diabetic complications, and other conditions. It plays an important role in skin aging as well. The accumulation of AGEs within the skin results in typical structural and functional changes that are colloquially known as sugar sag.[20]

AGEs have a large impact on the collagen and elastin fibers that maintain the structural framework of the skin and provide resilience and elasticity. Glycation results in intermolecular collagen cross-linking, resulting in increased stiffness and vulnerability to mechanical stimuli.[21] In addition, cross-linked collagen cannot be repaired as well. Collagen is highly susceptible to glycation, in part due to its long half-life, and may undergo up to a 50% increase in glycation over a lifetime.[22] Glycation is closely related to oxidation and inflammation as well. Glycation increases reactive oxygen species (ROS), further accelerating oxidative damage. Additionally, AGEs may bind to specialized cellular surface receptors called receptor for AGEs (RAGEs). When activated, RAGE triggers several cellular signaling pathways.[23] These further promote inflammation and altered cytokine expression.

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