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CANCER, AGEING and METABOLISM

CANCER, AGEING and METABOLISM. Ask… or txt: 858 212 4785. difficulties in being a long-lived MCO. cancer. ageing. difficulties in being a long-lived MCO. quantity. quality. cancer. cancer cells: differences are subtle. pathogens: differences are clearer.

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CANCER, AGEING and METABOLISM

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  1. CANCER, AGEING and METABOLISM

  2. Ask… or txt: 858 212 4785

  3. difficulties in being a long-lived MCO cancer ageing

  4. difficulties in being a long-lived MCO quantity quality

  5. cancer

  6. cancer cells: differences are subtle pathogens: differences are clearer

  7. what are other adaptive features of tumor cells? how are they different from normal cells? cell biology genomics proteomics metabolism

  8. fast-growing cells in midst of stationary cells F remove front layer F

  9. fast-growing cells in midst of stationary cells starved for oxygen lack of nutrients low O2 causes transcriptional response hypoxia-inducible factor: HIF1-a

  10. fast-growing cells in midst of stationary cells low oxygen HIF1-a increased glycolysis angiogenic factors

  11. “The prime cause of cancer is the replacement of the respiration of oxygen ... in normal body cells by fermentation of sugar” Otto Warburg 1956

  12. Warburg ca 1950s…

  13. “The prime cause of cancer is the replacement of the respiration of oxygen ... in normal body cells by fermentation of sugar” Otto Warburg 1956

  14. Craig Thompson, M.D. President, Memorial Sloan-Kettering

  15. Science, May 2009

  16. Warburg ca 2010…

  17. “The prime cause of cancer is the replacement of the respiration of oxygen ... in normal body cells by fermentation of sugar” Otto Warburg 1956 Tumor cells derive nearly all of their fatty acids from de novo synthesis Sidney Weinhouse 1953 what are the special features of tumor cell metabolism?

  18. Craig Thompson, M.D. President, Memorial Sloan-Kettering is glucose-dependent FA synthesis an “achilles heel” of tumor cells?

  19. remember citrate lyase? fig 21-10

  20. citrate lyase as an anabolic carbon source… fig 21-10

  21. FA synthesis in glycolytic tumor cells Hatzivassiliou et al. (2005) Cancer Cell 8, 1-11

  22. pre-developed drugs... citrate citrate lyase AcCoA statins cholesterol fatty acids

  23. Both AcCoA availability and NAD+ regeneration are blocked by inhibiting citrate lyase fig 21-10

  24. citrate lyase inhibitors

  25. Do citrate lyase inhibitors block tumor cell growth?

  26. Do citrate lyase inhibitors block tumor cell growth?

  27. A new metabolic pathway in cancer?

  28. A new metabolic pathway in cancer? ~ 80% of gliomas have a mutation in IDH1 cytoplasmic version of IDH, uses NADP+ mutation is always in R132, mostly R132H always heterozygous… why?

  29. A new metabolic pathway in cancer?

  30. A new metabolic pathway in cancer? metabolic profiling (metabolomics) revealed an abundance of 2-hydroxyglutarate… ??? could this be a product of the mutant IDH?

  31. A new metabolic pathway in cancer? mutant

  32. A new metabolic pathway in cancer! How does production of 2OH-glutarate benefit the glioma cancer cell?

  33. programmed cell death: apoptosis a dedicated signaling pathway for killing cells in MCOs apoptotic death has clear characteristics employed in development and in both intra- and inter cellular surveillance main player...

  34. The mitochondrion! one way that apoptosis is activated is by the regulated release of cytochrome c!

  35. The mitochondrion! one way that apoptosis is activated is by the regulated release of cytochrome c!

  36. difficulties in being a long-lived MCO quantity quality

  37. difficulties in being a long-lived MCO cancer aging

  38. difficulties in being a long-lived MCO in adult organisms (like us) many cells must live for the entire lifetime without replacement all organisms have finite lifespans

  39. old and young yeast

  40. old and young C. elegans 1 day old 13 days old

  41. old and young people

  42. The Search for The Fountain of Youth Ponce de Leon

  43. the only known mammalian longevity enhancer...

  44. the only known mammalian longevity enhancer... caloric restriction (CR) 30-40% balanced decrease 30% or more increase in longevity yeast, rotifers, flies, worms, fish, spiders mice, rats, birds

  45. how about in CR in humans or primates? Okinawan centenarians analysis

  46. how about in CR in humans or primates? Okinawan centenarians analysis One controlled human study

  47. how about in CR in humans or primates? Okinawan centenarians analysis One controlled human study Biosphere 2

  48. Biosphere 2

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