Without inflammation, infections would go unchecked and wounds would not heal; however, the process of inflammation and repair can also be harmful. As we age, the immune system becomes less effective and its capacity to manage the inflammatory activity is reduced. This can lead to chronic inflammation characterized by a slow but continuous production of free radicals and Matrix Metalloproteinases (MMP) causing wrinkles and sagging skin. The term “Inflammaging” was coined by Claudio Franceschi to describe the close relationship between aging and the cascade of inflammatory responses that lead to chronic inflammation. The level of chronic inflammation increases with aging and certain lifestyle or environmental factors or stressors including smoking, UV radiation and poor dietary habits.
Inflammaging is a useful clinical construct although Inflammatory responses are intended to be protective, because all the major age related diseases share an inflammatory pathogenesis. Inflammaging consists of a cascades of signaling pathways or processes at the molecular and cellular levels leading to the differences in expressions of immune and/or inflammatory response genes (cytokines, hormones, enzymes, etc). This rampant up-regulation of anti-stress responses in turn leads to the accumulation of molecular and cellular damages. Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process.When inflammation becomes chronic, these damages accumulate slowly, sometimes without symptoms for years but can lead to severe tissue deterioration. Chronic inflammation is, for this reason, also called “silent inflammation.”
The molecular and cellular biology of inflammaging process are also applicable to skin. The importance of chronic inflammation in the promotion of skin aging is being increasingly recognized and. The elevated circulating pro-inflammatory hormones such as prostaglandins, cytokines or histamines activate inflammatory cells or immune cells such as macrophages which can effectively produce ROS in order to destroy pathogens bt at the same time also cause oxidative damage to functioning bio-molecules such as DNA, proteins and lipids. Accumulated ROS in turn becomes the stimuli to induce a host of cytokine cascades that result in skin aging and photo-damage of skin. These changes are directly tied to the appearance of aging skin. Mediators of inflammation has been found to be increased in aging skin while body’s natural anti-inflammatory mediators are decreased in aging skin.
Inflammaging In Skin
proinflammatory mediators mechanism level in aging skin
COX (cyclooxygenase) COX, is the key enzymes involved in the development of inflammatory response. increased
5-LOX (5-lypooxygenase) 5-LOX is the key enzymes involved in the development of inflammatory response. increased
NF-kB one of the pro-inflammatory transcription factor lead to increased expression of pro-inflammatory mediators genes increased especially after sun exposure, UV radiation
inflammatory response mechanism level in aging skin
Matrix Metalloproteinases (MMP) degrade ECM (collagen, elastin), increased during inflammation, directly related to the aging appearance of skin increased
ROS (free radical) Macrophages produce reactive oxygen species (ROS) in order to attack infection, increased level cause aging skin appearance. An excess of ROS in the skin can make NF-kB chronically active leading to a continued release of inflammatory mediators and thus to chronic inflammation. increased
natural anti-inflammatory mediator mechanism level in aging skin
tissue inhibitors of MMPs (TIMPs) cellular inhibitors of MMPs decreased
transforming growth factor (TGF) 1. anti-inflammatory
2. TGF-β/Smad pathway is the major regulator of type I procollagen synthesis in human skin.decreased
Most of us know by now that sun exposure is the number one cause of wrinkles. Why? Skin reacts to the stress of those damaging UV rays with its own stress-response system, inflammation. UV radiation breaks down elastin and collagen causing cellular damage. Wrinkles are formed when the skin is repeatedly inflamed from UV exposure (Photoaging), cellular damage occurs and as the inflammation subsides/reduces the skin buckles inward, creating a crease. This type of wrinkle is called “static.”