Linda and Fori's Project

General Assignment

 * Mod 3 Final Project: Research Proposal
 * Begin to define your research proposal by making a wiki page to collect your ideas and resources (you can do this on one page with your partner or split the effort and each turn in an individual page). Keep in mind that your presentation to the class will ultimately need:
 * a brief project overview
 * sufficient background information for everyone to understand your proposal
 * a statement of the research problem and goals
 * project details and methods
 * predicted outcomes if everything goes according to plan and if nothing does
 * needed resources to complete the work
 * You can organize your wiki page along these lines or however you feel is most helpful. For now, focus on coming up with a research problem and giving a little background about it. *Print your user page(s) for next time, making sure it defines your topic, your idea and two or more references you've collected and summarized. Keep in mind that you're not committed to this idea - if you come up with something that you like better later on, that's fine.

Our Idea

 * Research Problems: One of the primary causes of wrinkles is extended chronic UV exposure, which leads to photo-aging. As photons bombard the surface of the skin, metalloproteases (MMP) are activated, elasticity is lost, and wrinkling occurs. The extracellular matrix of skin cells undergoes degradation: underlying proteins, such as collagen, and fibers, such as elastin, breakdown resulting in loss of mechanical intregrity and the formation of a wrinkle.


 * Research Goals: Attack the root cause of wrinkle formation by attempting to reverse and/or reduce skin matrix degradation by inhibiting collagenase, the metalloprotease that breaks down collagen. More specifically, the enzyme collagenase stimulates collagen formation in fibroblasts at low concentrations, but at high levels, collagenase causes degradation of and damage to collagen levels. MMP levels rise with increased sun exposure, age, and decreased estrogen levels. Our goal is to return MMP levels to concentrations similar to those during youth--levels which were sufficient to remove damaged skin matrix while preserving elasticity and a youthful visage.


 * Predicted outcomes:

Background Research Links
Metalloproteases
 * General Info
 * Key point: MMP are part of the balance of matrix synthesis and breakdown/recycling
 * MMP make sure old/damaged matrix gets degraded --> can be regenerated later
 * w/o: damage accumlates
 * with too much (as in aging): destruction of matrix! wrinkles!
 * elevated MMP levels - what factors?
 * Aging
 * Inflammation
 * Irritation
 * UV sun damage
 * Inhibitors of MMPs
 * How to inhibit MMP in order to conserve matrix?
 * drugs: doxycycline hyclate (MMP-1, 2, 8, 9)
 * eliminate environmental factors
 * anti-inflammatory: inflammation incr. MMP levels
 * plant/soy extracts

Other
 * Corrective Dermatology: Yesterday-Today-Tomorrow.
 * Information on Retinol & Retinoic Acid
 * Recent advances in characterizing biological mechanisms underlying UV-induced wrinkles: a pivotal role of fibrobrast-derived elastase.
 * up-reg fibroblast elastase --> wrinkles!
 * UVB irradiation --> activity of fibroblast elastases
 * confirmed: wrinkles = elastic fiber degradation
 * Zingiber officinale (L.) Rose extract inhibits fibroblast elastase
 * Animal studies: preventive effects against UVB wrinkles
 * HUman: improves wrinkle formation around corner of eye
 * Overall: UV --> cytokine --> incr. elastase --> deterioration of 3D architecture of elastic fibers --> wrinkles