2. Afia Osei-Ntansah Independent Research Reservoir High School Dr. Susan Michaelis

3. Learn about Hutchinson Gilford Progeria Syndrome (HGPS) Cause for HGPS Effects in Children with Progeria Possible Effects in Us (Primary Research) Conclusion

4. How many of you have ever seen the movie The Curious Case of Benjamin Button?

5. FALSE HEADLINES

6.  Progeria is a rare disease, but it doesn’t cause children to reverse in age, instead they age quicker.

7.  Symptoms of Progeria include...  dry, wrinkly skin  small jaw  hair loss & balding  growth failure  osteoporosis  and most fatal-- cardiovascular disease

8. Children with Progeria

9. Raise your hand if you are taking Biology or if you have already taken it.

10.  The mutation responsible for Progeria was found in the LMNA gene.  Even though the mutation is a silent mutation, it activates a splice site in this gene. But what does this all mean?

11. What are genes made up of?

12. DNA Nucleotides: A- adenine T- thymine C- cytosine G- guanine

13.  In Progeria, the DNA sequence of GGC becomes GGT. So this change is known a silent mutation because the amino acid (the building block for the protein to be made) of both of these sequences are the same.

14. What is a splice site? (here’s an example with mRNA)

15.  When this gene is not spliced properly, a protein is produced. The name of this protein is progerin and it quickly builds up in the bodies of children with Progeria. Research has also shown that it builds up in our bodies too.

16.  Children with Progeria are born looking normal, until the age of 1 &2.  It takes time for progerin to start causing problems.

17. 2 nuclei. Which is not affected by progerin?

18.  So because of nuclear blebbing, the control center or the brain of a cell is ruined. An unstable nucleus is an easy target for disease- like the diseases we see in Progeria.

19.  The FTI is able to reverse the strength that progerin has on cells. Left- Progeria cell without FTI Right- Cell treated with FTI Cells treated with an FTI had a more normal nucleus. Diseases were treated, but not cured. Weight improved, bone density improved, heart muscles were also strengthened.

20.  It’s effects proved to be limited  Took more than a year for results to show  Effects wore off quickly  Because it was a very expensive trial, only 50 out of the 200 children who needed treatment were able to get it  The results of the children were still greater than expected Farnesyltransferase Inhibitor (FTI)

21. So now, close your eyes and imagine how you think you will look at 80 years old. Raise your hand and tell me what you see.

22.  Wrinkly skin  Hair Loss  Osteoporosis  Cardiovascular Disease

23.  Statins are used in many medications in our normal population.  Mostly heart medicines- Levacor, Zocor  And a few bone strengthening drugs

24.  Research is being done on how FTIs and statins may work together better than just FTIs to stop the prenylation of progerin.  Prenylation- the addition of hydrophobic molecules to progerin

25.  Hydrophobic molecules make progerin accumulate faster, because of this, statins are needed to block this prenylation.

26. Think about these similarities. Is it possible that an aspect of a rare disease found only in 200 children worldwide can be related to the normal aging process?

27. Progerin is produced in both normal individuals and children with Progeria

28. Diseases found in children with Progeria are also found in the elderly.

29. Progerin is what causes these diseases in children with Progeria.

30. Can progerin cause age-related diseases in the normal aging population too?

31.  Dr. Susan Michaelis, Department of Cell Biology at John Hopkins University  Dr. Junko Oshima, Molecular and Cell Biology at UW  Dr. Ingrid Harten, Biology of Aging (progeriod syndromes) at UW  Dr. Tom Misteli, Senior Investigator at the NIH

32.  Dr. Harten at the University of Washington says, “we make a little bit of progerin all the time and it builds up and by the time that you are 70 or 80, you can see it and by then it will start to cause some problems.”

33.  Dr. Susan Michaelis says, “This could be [a factor for aging] and it could be a really important factor in some people and not very important in others.”

34.  Dr. Misteli a senior investigator at the National Institutes of Health (NIH) also says, “I don’t think it’s the reason why we age, but I think it certainly contributes.”

35. Progerin could be a contributing factor to aging in the elderly. There is a lot that is known about normal aging. This insight can be used to treat children with Progeria even better- giving mopre children hope.

38.  http://www.impawards.com/2008/curious_case_of_benjamin_button_ver12.html  http://giggsey.com/videos/index.php?type=films&film=565  http://simple.wikipedia.org/wiki/Alternative_splicing  http://www.imetum.tum.de/forschung/epigenetik/ allgemein/  http://en.wikipedia.org/wiki/Progeria  http://www.ridersplus.com/articles/clubs_and_rides/Ride_for_Progeria_printer.php  http://vectorblog.org/2012/09/first-ever-drug-trial-reverses-some-signs-of-aging-in-progeria/  http://www.intechopen.com/books/genetic-disorders/hutchinson-gilford-progeria-syndrome  http://abcnews.go.com/topics/lifestyle/health/progeria-syndrome.htm  http://www.laprensatoledo.com/Stories/2006/December27,2006/Kaylee.htm  http://www.scatterweb.net/top-10-weird-medical-conditions-that-are-still-not-fully-understood/  http://teamcarlyq.com/  http://www.youtube.com/watch?v=trFBZprV_eU  http://www.pinterest.com/Haleyrg123/progeria/  http://www.fia-lee.blogspot.com  sharron-harrysstory.blogspot.com  http://www.nj.com/news/local/index.ssf/2010/07/verona_family_is_hoping_for_a.html  http://www.astrochem.org/sci/Nucleobases.php  http://www.dailymail.co.uk/news/article-2537843/Touching-tribute-penned-Patriots-owner-Robert-Kraft- 17-year-old-rare-disease-died-HOURS-BEFORE-guest-honor-Patriots-play-game.html  http://www.vyperlook.com/amazing-incredible/hayley-okines-14-year-old-teenager-progeria-105-old  http://facepunch.com/showthread.php?t=1215772  http://www.wisegeek.org/what-is-a-banana-bag.htm  http://www.jerebeasleyreport.com/2008/12/capitol-hill-nursing-home/  http://www.progeriaresearch.org/  http://home.comcast.net/~neilswidey/fasttimes.htm  http://myhome.sunyocc.edu/~weiskirl/water.htm