| WEEK # | TOPICS | READINGS |
|---|---|---|
| 1 | Introduction and course overview | No Readings |
| 2 | Introduction to calorie restriction |
Weindruch, R., R. L. Walford, et al. "The Retardation of Aging in Mice by Dietary Restriction: Longevity, Cancer, Immunity and Lifetime Energy Intake." Journal of Nutrition 116 (1986): 641-54. Colman, R. J., R. M. Anderson, et al. "Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys." Science 325 (2009): 201-4. |
| 3 | Cellular senescence and telomerase |
Allsopp, R. C., H. Vaziri, et al. "Telomere Length Predicts Replicative Capacity of Human Fibroblasts." Proc Natl Acad Sci 89 (1992): 10114-18. ( Rudolph, K. L., S. Chang, et al. "Longevity, Stress Response, and Cancer in Aging Telomerase-deficient Mice." Cell 96 (1999): 701-12. |
| 4 | Premature aging syndromes |
Varga, R., M. Eriksson, et al. "Progressive Vascular Smooth Muscle Cell Defects in a Mouse Model of Hutchinson-Gilford Progeria Syndrome." Proc Natl Acad Sci 103 (2006): 3250-5. ( Kujoth, G. C., A. Hiona, et al. "Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian Aging." Science 309 (2005): 481-4. |
| 5 | Lifespan extension in model organisms |
Kennedy, B. K., N. R. Austriaco Jr., et al. "Mutation in the Silencing Gene SIR4 Can Delay Aging in S. cerevisiae." Cell 80 (1995): 485-96. Ayyadevara, S., C. Tazearslan, et al. "Caenorhabditis elegans PI3K Mutants Reveal Novel Genes Underlying Exceptional Stress Resistance and Lifespan." Aging Cell 8 (2009): 706-25. |
| 6 | Sirtuins in lifespan extension |
Kaeberlein, M., McVey M., et al. "The SIR2/3/4 Complex and SIR2 alone Promote Longevity in Saccharomyces cerevisiae by Two Different Mechanisms." Genes Dev 13 (1999): 2570-80. Herranz, D., M. Muñoz-Martin, et al. "Sirt1 Improves Healthy Ageing and Protects from Metabolic Syndrome-associated Cancer." Nature Communnication 1 (2010): 1-8. |
| 7 | Tor in model organisms |
Steffen, K. K., V. L. MacKay, et al. "Yeast Life Span Extension by Depletion of 60s Ribosomal Subunits is Mediated by Gcn4." Cell 133 (2008): 292-302. Hansen, M., S. Taubert, et al. "Lifespan Extension by Conditions that Inhibit Translation in Caenorhabditis elegans." Aging Cell 6 (2007): 95-110. |
| 8 | Field trip to Boston Data Aging Club meeting at Harvard Medical School
| No Readings |
| 9 | Oxidative stress theory of aging |
Pérez, V. I., R. Buffenstein, et al. "Protein Stability and Resistance to Oxidative Stress are Determinants of Longevity in the Longest-living Rodent, the Naked Mole-rat." Proc Natl Acad Sci 106 (2009): 3059-64. ( Schriner, S. E., N. J. Linford, et al. "Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria." Science 308 (2005): 1909-11. |
| 10 | Oxidative stress and aging: beneficial effects |
Schulz, T. J., K. Zarse, et al. "Glucose Restriction Extends C. elegans Life Span by Inducing Mitochondrial Respiration and Increasing Oxidative Stress." Cell Metab 6 (2007): 280-93. Lee, S-J, A. B. Hwang, et al. "Inhibition of Respiration Extends C. elegans Life Span via Reactive Oxygen Species that Increase HIF-1 Activity." Current Biology 20 (2010): 2131-36. |
| 11 | Reversing aging with drugs; activating sirtuins with resveratrol |
Baur, J. A., K. J. Pearson, et al. "Resveratrol Improves Health and Survival of Mice on a High-calorie Diet." Nature 444 (2006): 337-42. Um, J-H, S-J Park, et al. "AMP-Activated Protein Kinase-Deficient Mice are Resistant to the Metabolic Effects of Resveratrol." Diabetes 59 (2010): 554-63. ( |
| 12 | Student oral presentations
| No Readings |
| 13 | Reversing aging with drugs; inhibiting the TOR pathway with rapamycin |
Miller, R. A., D. E. Harrison, et al. "Rapamycin, but not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice." J Gerontol A Biol Sci Med Sci 66 (2011): 191-201. Spilman, P., N. Podlutskaya, et al. "Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-βeta Levels in a Mouse Model of Alzheimer's Disease." PLoS One 5 (2010): e9979. |
