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Resveratrol: A Real Anti-aging Product

By: Peter T. Pugliese, MD
Posted: November 25, 2008, from the December 2008 issue of Skin Inc. magazine.

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Resveratrol and cancer. Cancer is one of the ugliest words in the English language. More is known about cancer now than ever before, but scientists are still a long way from solving this complex disease. One characteristic of cancer cells is that they have escaped the normal growth-control mechanisms in the body. Normal cells are controlled by many genetic systems that maintain a series of checks and balances on all the cells to keep just the right number available at all times. When a cell becomes worn out, nonfunctional or abnormal, the body will usually destroy it. When dealing with a cancer cell, this is not the case; the cell becomes autonomous, and will continue to divide and grow more cancer cells. This is known as abnormal cellular proliferation. Cancer therapy is directed at killing the cancer cell or inhibiting its proliferation: either way, the cancer cell is destroyed.

When a cell is abnormal, it is literally destroyed by being taken apart by a genetic mechanism called apoptosis. The anti-proliferative activity of resveratrol that occurs in some cancer cell lines is believed to be due to the induction of apoptosis.10 It is suggested that the proliferation inhibition of resveratrol is caused by the arrest of the cell cycle. When a cell cannot be destroyed by an existing genetic mechanism, it will stop the division of the cell in one of four stages: G1, S, G2 or M. The molecular mechanisms associated with the anti-proliferative effects relate to two mechanisms—one is the activation of p53 and the other is the suppression of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). These are complex systems, but you can learn more about them by checking out these references.11, 12

Resveratrol and inflammation. Inflammation is a biological reaction that represents a complex host’s normal defense reaction to insult and stress, which can be either physiological or nonphysiological, including such agents as chemicals, drugs, oxidants and microbial entities. All inflammatory responses, whether acute or chronic, must be activated by well-coordinated, sequential events controlled by humoral and cellular reactions. ROS, including superoxide, hydroxyl radical, hydrogen peroxide and reactive nitrogen species (RNS), such as nitric oxide, are implicated in the inflammatory process.

The destructive effects of these ROS depends on their concentration and the microenvironment in which they are released. Normally the body can handle the ROS production, but when they are overproduced, such as when the body experiences sunburn or overeating, they become a major factor in tissue inflammation. Inflammatory responses usually proceed as follows: intracellular activation; infiltration of proinflammatory macrophages and lymphocytes, which are blood cells; increased vascular permeability; and finally tissue damage and cell death. In aging, the same process occurs, but it is slower and less violent.

Current research suggests that resveratrol blocks the inflammatory process in a rather complex way. NF-κB is a key step in the process of inflammation.13 Inhibition of NF-κB activity is a possible mechanism by which resveratrol exerts its anti-inflammatory activity. The exact mechanism by which resveratrol inhibits NF-κB activation remains uncertain, but studies have clearly shown that this action is real.14