March 10, 2010

SDSU BioScience Center UpData

By Roberta Gottlieb, M.D.

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coronary arteries

Researchers in the BioScience Center have been thinking about autophagy. Autophagy (literally "self-eating") is a process where cells recycle bits and pieces of themselves through a pathway involving an autophagosome, which then transports the material to be recycled to the lysosome. Although I usually don't get technical in these postings, TIME Magazine recently published a special report on longevity and mentioned the importance of autophagy in extending lifespan (TIMEHEALTH Feb 22, 2010). Autophagy can be induced by restricting calories or intermittent fasting, by drugs such as resveratrol or rapamycin, or by a compound present in semen, called spermidine. It appears that these all work through inducing autophagy. BSC researchers Kim Finley and Roberta Gottlieb have been studying autophagy for several years; Finley uses fruit flies to understand the role of autophagy in lifespan extension, and Gottlieb is looking at autophagy as a way to protect the heart.

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autophagosomes in a cross-section of a heart

More recently, autophagy has been shown to play important but complex roles in the immune system. That's where the BSC immunologists who now grace the third-floor Shiley Center for Cardiovascular Research are getting involved. They have been interested in how aging affects the immune system. It is well-known that the elderly are more vulnerable to infection, and do not respond as briskly to vaccination. Phyllis Linton has recently submitted a grant proposal to determine whether inducing autophagy can restore immune function in the elderly. Marilyn Thoman and Libby Virts have been studying various aspects of age-related immune deterioration, and are now exploring whether boosting autophagy can modify this process. Since autophagy becomes less efficient as the organism ages, the quest is to determine whether drugs or caloric restriction can normalize autophagy and immune function. Joy Phillips and Ed Morgan have been working for several years to develop a vaccine adjuvant (an adjuvant is something added to a vaccine to help boost the immune response) that might work better than current ones, and they are now exploring whether this adjuvant works in part by boosting autophagy. Ed Morgan is also working with graduate student Nikos Gurfield and the Gottlieb lab to determine if autophagy can be harnessed to enhance antigen presentation, with the goal of developing a vaccine for the parasite Trypanosoma cruzi which causes Chagas Disease, a chronic infection that damages the heart and leads to heart failure. The infection afflicts about 16 million people in Latin America and is being seen with increasing frequency in the U.S., in part due to immigration. However, the parasite, which spends part of its life cycle in a biting insect called the reduvid bug, is also present in the border states from Texas to California.

Because of the expanding interest in autophagy as it relates to the immune response and aging, the BSC investigators have scheduled a weekly meeting in the Kreitzer Conference Room. It appears that the BSC investigators have largely been bitten by "autophagy fever," and it seems to be a rich topic to mine, based on the publications coming from this work.