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Path517A - The Biology and Pathology of Aging
(updated 1/5/14)

Instructor:

Matt Kaeberlein   kaeber@uw.edu

           

Faculty Lecturers:

Alan Herr                alanherr@uw.edu

Dave Marcinek        dmarc@uw.edu

Junko Oshima         picard@uw.edu

Daniel Promislow     promislo@uw.edu

Norm Wolf              normwolf@u.washington.edu

Piper Treuting          treuting@uw.edu

 

Course Website:  

                        https://catalyst.uw.edu/workspace/kaeber/42631/

This course meets on Friday afternoons (2 - 4:20 PM) in the Health Sciences Building Room T-747


The course will be an overview of the biology of aging at the whole animal, organ, cellular, and molecular levels.

Required weekly readings can be downloaded from this website by clicking "files" or here.

 

Participation: Each of you is expected to participate in a 25 minute group presentation on one of the topics below. Topics will be chosen on the first day of class. In addition, each week you will be expected to answer prepared discussion questions and write a critical review on one of the weekly research papers. Please be sure to bring a printed copy of your assignment to class each week. (Online copies will not be accepted.)

 

Grading:  For those who registered for credit/no credit, you must turn in all of the assigned weekly questions/reviews and may have no more than one unexcused absence in order to receive a passing grade.  In addition you must participate in your assigned group presentation.

 

For those who registered for a numerical grade, you will receive a 4.0 if you satisfactorily complete all of your weekly assignments, attend all scheduled classes, and participate in your assigned group presentation.  Your grade will be reduced by 0.5 points for each missed class or missing assignment.  For example, if you miss one class and fail to turn in one assignment, your grade for the course will be 3.0. Failure to participate in a group presentation will result in 2.0 being deducted from your final course grade.

 

 

 

Course Schedule: 

 

Week 1 (Jan 10):    Introduction, selection of presentation groups, key concepts in aging

 

Lecture: Overview of aging research and model systems – Matt Kaeberlein


Week 2 (Jan 17): 

 

Student Presentation:  Nate Basisty, Ali Jafari

 

Paper Discussion:

 

Review Paper #1: Kaeberlein M. (2013). Longevity and aging. F1000prime reports 5, 5. 3590784

 

Classic Paper #1: Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R. (1993). A C. elegans mutant that lives twice as long as wild type. Nature 366, 461-464.

 

Classic Paper #2:  Sinclair DA, Guarente L. (1997). Extrachromosomal rDNA circles--a cause of aging in yeast. Cell 91, 1033-1042.

 

Lecture: Cell senescence, telomeres and aging – Junko Oshima

 

 

Week 3 (Jan 24): 

 

Student Presentation: Bonnie Hastings, Rick Rice, Charisma Enam, Ying He

                                  

Paper Discussion:

 

Review Paper #1:  1.  F. Rodier, J. Campisi, Four faces of cellular senescence. J Cell Biol 192, 547 (Feb 21, 2011).

 

Research Paper #1: 1.            D. Munoz-Espin et al., Programmed cell senescence during mammalian embryonic development. Cell 155, 1104 (Nov 21, 2013).

 

Research Paper #2: 1.            B. Bernardes de Jesus et al., Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO molecular medicine 4, 691 (Aug, 2012).

 

Lecture: Pathology of mouse aging – Piper Treuting

 

 

Week  (Jan 31): 

 

 

Student Presentation: Farzin Eshaghi, Nic LeTexier, Tiffany Yang

 

Paper Discussion:

 

Review Paper #1:  Ladiges W, Ikeno Y, Liggitt D, Treuting PM. (2013). Pathology is a critical aspect of preclinical aging studies. Pathobiology of aging & age related diseases 3. 3749367

 

Research Paper #1: Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schroder S, Adler T, Afonso LC, Aguilar-Pimentel JA, Becker L, Garrett L, Hans W, Hettich MM, Holtmeier R, Holter SM, Moreth K, Prehn C, Puk O, Racz I, Rathkolb B, Rozman J, Naton B, Ordemann R, Adamski J, Beckers J, Bekeredjian R, Busch DH, Ehninger G, Graw J, Hofler H, Klingenspor M, Klopstock T, Ollert M, Stypmann J, Wolf E, Wurst W, Zimmer A, Fuchs H, Gailus-Durner V, Hrabe de Angelis M, Ehninger D. (2013). Rapamycin extends murine lifespan but has limited effects on aging. The Journal of clinical investigation 123, 3272-3291. 3726163

 

Research Paper #2: Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE, Hejtmancik JF, Nadon N, Strong R, Wood LK, Woodward MA, Miller RA. (2012). Rapamycin slows aging in mice. Aging Cell 11, 675-682. 

 

Lecture: Mutations, genomic stability and aging – Alan Herr

 

 


Week 5 (Feb 7):  

 

Student Presentation: Natalie Miller, Madeline Sandoval, Kate Johnson, Mike Stolly

 

Paper Discussion:

Review Paper #1:  Kennedy SR, Loeb LA, Herr AJ. (2012). Somatic mutations in aging, cancer and neurodegeneration. Mech Ageing Dev 133, 118-126. 3325357

Research Paper #1: Kennedy SR, Salk JJ, Schmitt MW, Loeb LA. (2013). Ultra-sensitive sequencing reveals an age-related increase in somatic mitochondrial mutations that are inconsistent with oxidative damage. PLoS Genet 9, e1003794. 3784509

Research Paper #2: Safdar A, Bourgeois JM, Ogborn DI, Little JP, Hettinga BP, Akhtar M, Thompson JE, Melov S, Mocellin NJ, Kujoth GC, Prolla TA, Tarnopolsky MA. (2011). Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice. Proc Natl Acad Sci U S A 108, 4135-4140. 3053975

 

Lecture: Oxidative stress and the free radical theory of aging– Norm Wolf

 

Week 6 (Feb 14): 

 

Student Presentation: Benjamin Curtis, Anthony Bui, Rang Gao, Rasmus Moeller

 

Paper Discussion:

Review Paper #1:  Perez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, Richardson A. (2009). Is the oxidative stress theory of aging dead? Biochim Biophys Acta 1790, 1005-1014. 2789432

Classic Paper #1: Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS. (2005). Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308, 1909-1911. 

Research Paper #1: Perez VI, Buffenstein R, Masamsetti V, Leonard S, Salmon AB, Mele J, Andziak B, Yang T, Edrey Y, Friguet B, Ward W, Richardson A, Chaudhuri A. (2009). Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat. Proc Natl Acad Sci U S A 106, 3059-3064. 2651236

Faculty Lecture: Progeria – Junko Oshima

 

 

Week 7 (Feb 21): 

 

Student Presentation: William Valente, Natalie Vandeven, Martha Delaney

 

Paper Discussion:
 

Review Paper #1:  Coppedè F. Premature aging syndrome. Adv Exp Med Biol. 2012;724:317-31.

Classic Paper #1: Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.  Nature. 2003 May 15;423(6937):293-8.

Classic Paper #2: Chang S, Multani AS, Cabrera NG, Naylor ML, Laud P, Lombard D, Pathak S, Guarente L, DePinho RA. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet. 2004 Aug;36(8):877-82.

Faculty Lecture: Comparative biology of aging – Daniel Promislow


Week 8 (Feb 28): 

 

Student Presentation: Valerie Tryon, Alex Chen, Chris Schaupp, Mike Zhang

 

Paper Discussion:

Review Paper #1:  Moorad JA, Promislow DE Aging and Menopause. In Princeton Guide to Evolution, Losos J, ed.

Classic Paper #1: Williams GC. (1957). Pleiotropy, natural selection, and the evolution of senescence. Evolution 11, 398-411. 

Research Paper #1: Tian X, Azpurua J, Hine C, Vaidya A, Myakishev-Rempel M, Ablaeva J, Mao Z, Nevo E, Gorbunova V, Seluanov A. (2013). High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature 499, 346-349.  PMC: 3720720

Lecture: Mitochondria and aging: Beyond free radicals – Dave Marcinek


Week 9 (Mar 7): 

 

Student Presentation: Ellen Quarles, Laura Taylor, Ana Dinca

 

Paper Discussion:

Review Paper #1:  Sohal, R.S. and W.C. Orr, The redox stress hypothesis of aging. Free Radic Biol Med, 2012. 52(3): p. 539-55.

Research Paper #1: Lopez-Lluch, G., et al., Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proc Natl Acad Sci U S A, 2006. 103(6): p. 1768-73.

Research Paper #2: Durieux, J., S. Wolff, and A. Dillin, The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell, 2011. 144(1): p. 79-91.

Lecture: Conserved pathways of aging – Matt Kaeberlein

 


Week 10 (Mar 14):

 

Student Presentation: Chun-Chi Lu, Mitchell Lee

 

Paper Discussion:

 

Lecture: Interventions and the future of aging research – Matt Kaeberlein

 

 

 

Send questions about this workspace to MATT R KAEBERLEIN​.