Cephalon, on 25 December 2010 - 07:30 PM, said:
I'm not sure I'm up to date with all supplements to avoid while doing CR.
From what I understand
a) nicotinamide and
might have negative impact on CR effects. are there any other forms of Vitamin B3 to avoid during CR?
I'm just about starting CR and want to make sure my (efforts) are not all for nothing.
Congratulations on starting CR-- a healthy way of living indeed. The question you asked is important -- a question I frequently discuss in CR way teleconferences and also here on this forum
You may find this post helpful: using Calorie Restriction Sicence to Select Supplements
I think SIRT2 is important, along with any number of energy-sensitive regulators that become active when CR is practiced. As you enjoy your new CR life, I suggest taking a look at studies like the one below and others cited in the references. Then carefully consider any supplements you take that may conflict with the pathways you have learned about.
Good luck with your CR life!
SIRT1 Negatively Regulates the Mammalian Target of Rapamycin
Hiyaa Singhee Ghosh1¤, Michael McBurney2, Paul D. Robbins1*
The IGF/mTOR pathway, which is modulated by nutrients, growth factors, energy status and cellular stress regulates aging in various organisms. SIRT1 is a NAD+ dependent deacetylase that is known to regulate caloric restriction mediated longevity in model organisms, and has also been linked to the insulin/IGF signaling pathway. Here we investigated the potential regulation of mTOR signaling by SIRT1 in response to nutrients and cellular stress. We demonstrate that SIRT1 deficiency results in elevated mTOR signaling, which is not abolished by stress conditions. The SIRT1 activator resveratrol reduces, whereas SIRT1 inhibitor nicotinamide enhances mTOR activity in a SIRT1 dependent manner. Furthermore, we demonstrate that SIRT1 interacts with TSC2, a component of the mTOR inhibitory-complex upstream to mTORC1, and regulates mTOR signaling in a TSC2 dependent manner.
These results demonstrate that SIRT1 negatively regulates mTOR signaling potentially through the TSC1/2 complex.
Citation: Ghosh HS, McBurney M, Robbins PD (2010) SIRT1 Negatively Regulates the Mammalian Target of Rapamycin. PLoS ONE 5(2): e9199. doi:10.1371/journal.pone.0009199
1. Chen D, Guarente L (2007) SIR2: a potential target for calorie restriction mimetics. Trends Mol Med 13: 64–71. Find this article online
2. Boily G, Seifert EL, Bevilacqua L, He XH, Sabourin G, et al. (2008) SirT1 regulates energy metabolism and response to caloric restriction in mice. PLoS ONE 3: e1759. Find this article online
3. Guarente L, Picard F (2005) Calorie restriction–the SIR2 connection. Cell 120: 473–482. Find this article online
4. Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289: 2126–2128. Find this article online
5. Bordone L, Cohen D, Robinson A, Motta MC, van Veen E, et al. (2007) SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6: 759–767. Find this article online
6. Sommer M, Poliak N, Upadhyay S, Ratovitski E, Nelkin BD, et al. (2006) DeltaNp63alpha overexp
ression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. Cell Cycle 5: 2005–2011. Find this article online
7. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, et al. (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303: 2011–2015. Find this article online
8. Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, et al. (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305: 390–392. Find this article online
9. Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410: 227–230. Find this article online
10. Berdichevsky A, Viswanathan M, Horvitz HR, Guarente L (2006) C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell 125: 1165–1177. Find this article online
11. Lin SJ, Kaeberlein M, Andalis AA, Sturtz LA, Defossez PA, et al. (2002) Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 418: 344–348. Find this article online
12. Kaeberlein M, Kirkland KT, Fields S, Kennedy BK (2004) Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol 2: E296. Find this article online
13. Kaeberlein M, Powers RW 3rd, Steffen KK, Westman EA, Hu D, et al. (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310: 1193–1196. Find this article online
14. Inoki K, Li Y, Xu T, Guan KL (2003) Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 17: 1829–1834. Find this article online
15. Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J (2003) Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 13: 1259–1268. Find this article online
16. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, et al. (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14: 885–890. Find this article online
17. Medvedik O, Lamming DW, Kim KD, Sinclair DA (2007) MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae. PLoS Biol 5: e261. Find this article online
18. Aarmour SM JB, Sherry N. Hsieh SN, Land-Bracha A, Thomas SM, Sinclair DA (2009) Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy. Aging 1: 515–528. Find this article online
19. Demidenko ZN, Blagosklonny MV (2009) At concentrations that inhibit mTOR, resveratrol suppresses cellular senescence. Cell Cycle 8: 1901–1904. Find this article online
20. MV. B (2009) Inhibition of S6K by resveratrol: In search for the purpose. Aging 1: 511–514. Find this article online
21. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, et al. (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460: 392–395. Find this article online
22. Schmelzle T, Hall MN (2000) TOR, a central controller of cell growth. Cell 103: 253–262. Find this article online
23. Ghosh HS, Spencer JV, Ng B, McBurney MW, Robbins PD (2007) Sirt1 interacts with transducin-like enhancer of split-1 to inhibit NF-kappaB mediated transcription. Biochem J. Find this article online
24. Jin Q, Yan T, Ge X, Sun C, Shi X, et al. (2007) Cytoplasm-localized SIRT1 enhances apoptosis. J Cell Physiol 213: 88–97. Find this article online
25. Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y (2007) Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem 282: 6823–6832. Find this article online
26. Zhang H, Cicchetti G, Onda H, Koon HB, Asrican K, et al. (2003) Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR. J Clin Invest 112: 1223–1233. Find this article online
27. Potter CJ, Huang H, Xu T (2001) Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105: 357–368. Find this article online
28. Dasgupta B, Milbrandt J (2007) Resveratrol stimulates AMP kinase activity in neurons. Proc Natl Acad Sci U S A 104: 7217–7222. Find this article online
29. Zhang J (2006) Resveratrol inhibits insulin responses in a SirT1-independent pathway. Biochem J 397: 519–527. Find this article online
30. Canto C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, et al. (2009) AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 458: 1056–1060. Find this article online
31. Araki T, Sasaki Y, Milbrandt J (2004) Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 305: 1010–1013. Find this article online
32. Bedalov A, Simon JA (2004) Neuroscience. NAD to the rescue. Science 305: 954–955. Find this article online
33. Berger Z, Ravikumar B, Menzies FM, Oroz LG, Underwood BR, et al. (2006) Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum Mol Genet 15: 433–442. Find this article online
34. Chen J, Zhou Y, Mueller-Steiner S, Chen LF, Kwon H, et al. (2005) SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. J Biol Chem 280: 40364–40374. Find this article online
35. Li X, Alafuzoff I, Soininen H, Winblad B, Pei JJ (2005) Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain. FEBS J 272: 4211–4220. Find this article online
36. Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, et al. (2005) Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet 37: 349–350. Find this article online
37. Qin W, Yang T, Ho L, Zhao Z, Wang J, et al. (2006) Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem 281: 21745–21754. Find this article online
38. Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, et al. (2004) Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 36: 585–595. Find this article online
39. Pattingre S, Espert L, Biard-Piechaczyk M, Codogno P (2008) Regulation of macroautophagy by mTOR and Beclin 1 complexes. Biochimie 90: 313–323. Find this article online
40. Yang YP, Liang ZQ, Gu ZL, Qin ZH (2005) Molecular mechanism and regulation of autophagy. Acta Pharmacol Sin 26: 1421–1434. Find this article online
41. Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, et al. (2008) A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci U S A. Find this article online
42. Narala SR, Allsopp RC, Wells TB, Zhang G, Prasad P, et al. (2008) SIRT1 Acts as a Nutrient-sensitive Growth Suppressor and its Loss is Associated with Increased AMPK and Telomerase Activity. Mol Biol Cell. Find this article online
43. McBurney MW, Yang X, Jardine K, Hixon M, Boekelheide K, et al. (2003) The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis. Mol Cell Biol 23: 38–54. Find this article online
Edited by Michael, 01 January 2011 - 04:09 PM.