Researchers at UCLA have found that sulforaphane, a chemical in broccoli and other cruciferous vegetables, switches on a set of antioxidant genes and enzymes in specific immune cells. The cells then fight the harmful effects of free radical molecules that can damage cells and lead to disease. The discovery could hold a key to renovating the body’s immunity, which declines as we age.
The study, published in the Journal of Allergy and Clinical Immunology online 06 March 2008, was led by Dr. Andre Nel, chief of nanomedicine at the David Geffen School of Medicine at UCLA.
“The mysteries of aging have always intrigued man,” said Dr. Nel. “While we have known for some time that free radicals are important in aging, most of the past attention has focused on the mechanisms that produce free radicals rather than addressing the pathways used by the body to suppress their production."
A dynamic equilibrium exists in the body between the mechanisms that lead to increased free radical production and those antioxidant pathways that help combat free radicals.
“Our study contributes to the growing understanding of the importance of these antioxidant defense pathways that the body uses to fight free radicals,” said Nel, a practicing clinical allergist and immunologist at the Geffen School. “Insight into these processes points to ways in which we may be able to alleviate the effects of aging."
Sulforaphane vs. Oxidants
The tricky balance between pro-oxidant and antioxidant forces in the body could determine the outcome of many disease processes that are associated with aging, including cardiovascular disease, degenerative joint diseases and diabetes, as well as the decline in efficiency of the immune system’s ability to protect against infectious agents.
“As we age, the ability of the immune system to fight disease and infections and protect against cancer wears down as a result of the impact of oxygen radicals on the immune system,” Nel said.
According to this study, the ability of aged tissues to reinvigorate their antioxidant defense can play an important role in reversing much of the negative impact of free radicals on the immune system. However, until this current study, the extent to which antioxidant defense can impact the aging process in the immune system was not properly understood.
Other cruciferous vegetables include brussel sprouts, broccoli, cabbage, cauliflower, bok choy, kale, collards, broccoli sprouts, chinese broccoli, broccoli raab, kohlrabi, mustard, turnip, radish, rocket, and watercress.
Previous studies have shown that consumption of broccoli sprouts is effective at inhibiting Helicobacter pylori growth,; sulforaphane was identified as one of the active agents.
“Our defense against oxidative stress damage may determine at what rate we age, how it will manifest and how to interfere in those processes,” Nel said. “In particular, our study shows that a chemical present in broccoli is capable of stimulating a wide range of antioxidant defense pathways and may be able to interfere with the age-related decline in immune function."
Of Mice and Broccoli
The UCLA team not only found that the direct administration of sulforaphane in broccoli reversed the decline in cellular immune function in old mice, but they witnessed similar results when they took individual immune cells from old mice, treated those cells with the chemical outside the body and then placed the treated cells back into a recipient animal.
In particular, the scientists discovered that dendritic cells, which introduce infectious agents and foreign substances to the immune system, were particularly effective in restoring immune function in aged animals when treated with sulforaphane.
“We found that treating older mice with sulforaphane increased the immune response to the level of younger mice,” said Hyon-Jeen Kim, first author and research scientist at the Geffen School.
To find out how the chemical in broccoli raised the immune system’s response, the UCLA group verified that sulforaphane interacts with a protein called Nrf2, which serves as a master regulator of the body’s overall antioxidant response and is capable of switching on hundreds of antioxidant and rejuvenating genes and enzymes.
Nel said that the chemistry leading to activation of this gene-regulation pathway could be a platform for drug discovery and vaccine development to boost the decline of immune function in elderly people.
“This is a radical new way of thinking in how to increase the immune function of elderly people to possibly protect against viral infections and cancer,” Nel said. “We may have uncovered a new mechanism by which to boost vaccine responses by using a nutrient chemical to impact oxidant stress pathways in the immune system."
The next step will be further studies to see how these findings could translate to humans.
Nrf2 activation by sulforaphane restores the age-related decrease of TH1 immunity: Role of dendritic cells Hyon-Jeen Kim, Berenice Barajas, Meiying Wang, Andre E. Nel The Journal of Allergy and Clinical Immunology DOI: 10.1016/j.jaci.2008.01.016
Zhang Y, Talalay P, Cho CG, Posner GH. A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci 1992;89:2399403
Fahey JW, Haristoy X, Dolan PM, Kensler TW, Scholtus I, Stephenson KK, Talalay P, Lozniewski A (May 2002). “Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors.”. PMID 12032331
_ Images:, credit: whologwhy, Stef Yau, Creative Commons License _