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Biology of Aging
November 15 - 19
Responsible: Sandra Cardoso
Biology of Aging Program

Organizers: Paula I Moreira (pismoreira@gmail.com) and Sandra Morais Cardoso (smacardoso@yahoo.com)

Marcia c Haigis (Harvard Medical School, Boston, USA)
Raquel Seiça (Universidade de Coimbra, Coimbra, Portugal)
Paula Agostinho (Universidade de Coimbra, Coimbra, Portugal)
Emília Duarte (Universidade de Coimbra, Coimbra, Portugal)
Ana Duarte (Universidade de Coimbra, Coimbra, Portugal)
Paula I Moreira (Universidade de Coimbra, Coimbra, Portugal)
Sandra Morais Cardoso (Universidade de Coimbra, Coimbra, Portugal)

Organization and Goals
The Course lectures will be open to the general public and Grant Proposal discussions will be made by student with pre-assigned papers/themes. Those are open to all CNC-PhD students, not only BEB students. Who wish to attend/be evaluated (please contact the course coordinators).
Students will have access to papers that will be made available (in BEB’s page) previous to the course. Presentations should be prepared and given together.


Monday (15 Nov 2010),
9h30: Introduction to the course, summary of course goals and student goals.
10h00-11h00: Biology of Aging (SM Cardoso)
11h00-11h15: Break
11h15-12h15: The Aging Brain (PI Moreira)

15h00-17h00: Tutorial distribution of papers relevant to the course.

Tuesday, (16 Nov 2010)
9h30-10h30: Inflammation and Aging (P Agostinho)
10h30-10h45: Break
10h45-11h45: Oxidative Stress in Aging (A Duarte)
11h45-12h00: Break
12h00-13h00: Age-related changes in glucose homeostasis (R Seiça)

15h00-17h30: Grant Proposal

Wednesday, (17 Nov 2010)
10h00-11h00: Mitochondrial role in the Aging process (P Moreira)
11h00-11h30: Break
11h30-12h30: Autophagy and its modulation in Aging (SM Cardoso)

14h30-15h30: The coordination of nuclear and mitochondrial communication during aging. (MC Haigis)
15h30-17h30: Grant Proposal

Thursday, (18 Nov 2010)
9h30-10h30: Mammalian sirtuins role in aging. (MC Haigis)
10h30-10h45: Break
10h45-11h45: Therapeutic potential of sirtuins: the in vivo evidence? (MC Haigis)
11h45-12h00: Break
12h00-13h00: Cellular senescence: from the cell to the organism and back (E Duarte)

15h00-17h30: Grant Proposal
18h00: Social Event

Friday(19 Nov 2010)
10h00-13h00: Who is interested in Aging and Age-related disorders?
We invite all CNC PIs to attend to this informal meeting to discuss this topic with Marcia C Haigis and with each other.
In order to the organizers plan in advance these get together, a registration is mandatory.
Short presentations by students (15 min):
“Melatonin alters cell death processes in response to age-related oxidative stress in the brain of senescence-accelerated mice” (IV Naredo)
“Chronic hypoxia potentiates age-related oxidative imbalance in brain vessels” (C Carvalho)
“Mitochondrial metabolism in age related PD” (AR Esteves)
“Age and gender effects on brain mitochondrial function in 3xTg-AD mice: a comparative study” (S Cardoso)

16h00:CNC Seminar
(MC Haigis)

Invited Speakers

Marcia C Haigis (Assistant Professor, Department of Pathology Harvard Medical School)
Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010;5:253-95.
Finley LW, Haigis MC. The coordination of nuclear and mitochondrial communication during aging and calorie restriction. Ageing Res Rev. 2009 Jul;8(3):173-88.
Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell. 2006 Sep 8;126(5):941-54.

Raquel Seiça (Professor of Physiology at Medical School, University of Coimbra, Portugal)
Sena CM, Louro T, Matafome P, Nunes E, Monteiro P, Seiça R. Antioxidant and vascular effects of gliclazide in type 2 diabetic rats fed high-fat diet. Physiol Res. 2009;58(2):203-9. Epub 2008 Apr 1
Sena CM, Proença T, Nunes E, Santos MS, Seiça RM. The effect of soybean oil on glycaemic control in Goto-kakizaki rats, an animal model of type 2 diabetes. Med Chem. 2008 May;4(3):293-7.
Nunes E, Peixoto F, Louro T, Sena CM, Santos MS, Matafome P, Moreira PI, Seiça R. Soybean oil treatment impairs glucose-stimulated insulin secretion and changes fatty acid composition of normal and diabetic islets. Acta Diabetol. 2007 Sep;44(3):121-30.

Emília Duarte (Assistant Professor at Science and Technology School, University of Coimbra, Portugal)
Cristóvão AC, Saavedra A, Fonseca CP, Campos F, Duarte EP, Baltazar G. (2010) Microglia of rat ventral midbrain recovers its resting state over time in vitro: Let microglia rest before work. J Neurosci Res. 88(3):552-62.
Saavedra A, Baltazar G and Duarte EP. (2008)  Driving GDNF expression: The green and the red traffic lights. Prog Neurobiol. 86, 186-215. 
Saavedra A, Baltazar G and Duarte EP. (2007) Interleukin-1b mediates GDNF up-regulation upon dopaminergic injury in ventral midbrain cell cultures. Neurob. Dis. 25, 92-104.

Paula Agostinho (Assistant Researcher, at Medical School, University of Coimbra, Portugal)
Lopes JP, Oliveira CR, Agostinho P. Neurodegeneration in an Abeta-induced model of Alzheimer s disease: the role of Cdk5. Aging Cell. 2010 Feb;9(1):64-77.
Lopes JP, Blurton-Jones M, Yamasaki TR, Agostinho P, LaFerla FM. Activation of cell cycle proteins in transgenic mice in response to neuronal loss but not amyloid-beta and tau pathology. J Alzheimers Dis. 2009 Mar;16(3):541-9.
Matos M, Augusto E, Oliveira CR, Agostinho P. Amyloid-beta peptide decreases glutamate uptake in cultured astrocytes: involvement of oxidative stress and mitogen-activated protein kinase cascades. Neuroscience. 2008 Oct 28;156(4):898-910.

Ana Duarte (Pos-Doc Fellow at CNC, Portugal)
Duarte AI, Santos P, Oliveira CR, Santos MS, Rego AC. Insulin neuroprotection against oxidative stress is mediated by Akt and GSK-3beta signaling pathways and changes in protein expression. Biochim Biophys Acta. 2008 Jun;1783(6):994-1002.
Duarte AI, Proença T, Oliveira CR, Santos MS, Rego AC. Insulin restores metabolic function in cultured cortical neurons subjected to oxidative stress. Diabetes. 2006 Oct;55(10):2863-70.
Duarte AI, Santos MS, Oliveira CR, Rego AC. Insulin neuroprotection against oxidative stress in cortical neurons--involvement of uric acid and glutathione antioxidant defenses. Free Radic Biol Med. 2005 Oct 1;39(7):876-89.

Paula I Moreira (Teaching Assistant of Physiology at Medical School, University of Coimbra, Portugal)
Correia S., Moreira P.I. (2010) Hypoxia-inducible factor 1: a new hope to counteract neurodegeneration? J. Neurochem. 112, 1-12.
Wang X., Su B., Siedlak S.L., Moreira P.I., Fujioka H., Wang Y., Casadesus G., Zhu X. (2008) Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc. Natl. Acad. Sci. USA 105, 19318-23.
Moreira P.I., Siedlak S.L., Wang X., Santos M.S., Oliveira C.R., Tabaton M., Nunomura A., Szweda L.I., Aliev G., Smith M.A., Zhu X., Perry G. (2007) Autophagocytosis of mitochondria is prominent in Alzheimer disease J. Neuropathol. Exp. Neurol. 66, 525-532.

Sandra M Cardoso (Teaching Assistant of Molecular and Cellular Biology at Medical School, University of Coimbra, Portugal)
Esteves AR, Arduíno DM, Swerdlow RH, Oliveira CR, Cardoso SM. (2010) Dysfunctional mitochondria uphold calpain activation: contribution to Parkinson’s disease pathology. Neurobiol Dis. 37(3):723-30.
Arduino DM, Esteves AR, Oliveira CR and Cardoso SM (2010) Mitochondrial Metabolism Modulation: A New Therapeutic Approach for Parkinson´s Disease. CNS Neurol Disord Drug Targets. 9(1):105-19.
Esteves A.R.F., Arduíno DM., Swerdlow R.H., Oliveira C.R. and Cardoso S.M. (2008) Oxidative Stress potentiates alpha-synuclein oligomerization in PD Cybrids. Antioxi Redox Signal 11(3): 439-448

Grant Proposals
Presentation should be prepared together and given together—one presentation, essentially. Three specific Aims is often a good number though anywhere from 2-5 can be quite reasonable. These aims should be listed in bullet point form underneath the title of the proposal. You may also employ sub-aims if you prefer (Aim 1A, Aim 1B, etc). Take care that the proposal has a sensible structure: the title should outline the major and general aim, which should be accomplished via several more specific aims, which themselves will be achieved by means of specific experiments.
The proposal should not entirely hinge on one experiment that may or may not work. The proposal should not be narrow but should address a significant issue in a deep manner, leading to a new level of understanding of that problem. A clearly defined hypothesis will help in developing your proposal. Normally grants work within the framework of a specific number of man-years to perform, anything from 3-6 man-years is most reasonable, but it is really up to you. Shorter is better, all things being equal, so that you can do justice to individual experiments. The subject matter should be related in some way to the paper assigned to the group, but does not have to be direct follow up work. Direct follow-up is OK too but make sure there are new ideas there. Do not hesitate to discuss whether a general proposal idea is appropriate with course faculty, but faculty input should be only general, they should not “fashion” the proposal actively in advance. If you wish to work on this in advance of the course meeting, you can contact them by email. Feasibility and creativity are both important in evaluating the proposal, but creativity more so. Try not to only propose familiar experiments. Consider multiple approaches for testing your hypothesis (for example, combining genetic and biochemical approaches). Prepare a powerpoint presentation outlining the proposal and diagramming some of the central experiments you propose. Consider in this powerpoint version necessary controls and pitfalls, and the significance of the project you propose. Non-presenters should discuss the merits of the proposed experiments—whether the problem is a good one, whether the experiments effectively address the problem and will give interpretable results, whether they could actually be done in practice, whether necessary controls have been provided, whether still other experiments should be considered, and, assuming that everything goes to plan, whether the information gained would deliver a significant advance in our understanding of the subject matter.
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