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Featured ArticleArticles, Neurobiology of Disease

A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration

Johannes Gräff, Martin Kahn, Alireza Samiei, Jun Gao, Kristie T. Ota, Damien Rei and Li-Huei Tsai
Journal of Neuroscience 22 May 2013, 33 (21) 8951-8960; DOI: https://doi.org/10.1523/JNEUROSCI.5657-12.2013
Johannes Gräff
1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences and
2Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and
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Martin Kahn
1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences and
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Alireza Samiei
1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences and
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Jun Gao
1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences and
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Kristie T. Ota
1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences and
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Damien Rei
1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences and
2Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and
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Li-Huei Tsai
1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences and
2Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and
3Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142
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Article Information

DOI 
https://doi.org/10.1523/JNEUROSCI.5657-12.2013
PubMed 
23699506
Published By 
Society for Neuroscience
History 
  • Received December 11, 2012
  • Revision received March 6, 2013
  • Accepted March 30, 2013
  • First published May 22, 2013.
  • Version of record published May 22, 2013.
Copyright & Usage 
Copyright © 2013 the authors 0270-6474/13/338951-10$15.00/0

Author Information

  1. Johannes Gräff1,2,
  2. Martin Kahn1,
  3. Alireza Samiei1,
  4. Jun Gao1,
  5. Kristie T. Ota1,
  6. Damien Rei1,2, and
  7. Li-Huei Tsai1,2,3
  1. 1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences and
  2. 2Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and
  3. 3Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142
  • K. T. Ota's present address: Laboratory of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT 06508.

View Full Text

Author contributions

  1. Author contributions: J. Gräff, D.R., and L.-H.T. designed research; J. Gräff, M.K., A.S., J. Gao, K.T.O., and D.R. performed research; L.-H.T. contributed unpublished reagents/analytic tools; J. Gräff, M.K., J. Gao, K.T.O., and L.-H.T. analyzed data; J. Gräff and L.-H.T. wrote the paper.

  • K. T. Ota's present address: Laboratory of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT 06508.

View Abstract

Disclosures

    • Received December 11, 2012.
    • Revision received March 6, 2013.
    • Accepted March 30, 2013.
  • This work was supported by a Swiss National Science Foundation Grant for Prospective Researchers (J. Gräff), the Theodor and Ida Herzog-Egli Foundation (M.K.), and the Glenn Foundation for Medical Research and NIH Grant PO1 AG027916 (L.-H.T.). L.-H.T. is an HHMI investigator. We thank Vipin X. Suri and Jim Ellis from Sirtris-GSK for the SRT3657 compound, Maria Ericsson for the electron microscopy experiments, Katie Schlieper and Mali Taylor for mouse colony maintenance and the oral gavage, Alison Mungenast for text editing, and Matthew M. Dobbin for fruitful scientific discussions. Sirtris Pharmaceuticals contributed to this study in providing and characterizing SRT3657 under a material transfer agreement.

  • L.-H.T. is a scientific advisor of Sirtris-GSK.

  • Correspondence should be addressed to Li-Huei Tsai at the above address. lhtsai{at}mit.edu

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May 20133707247596
Jun 20131286153238
Jul 20133555369
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Jan 20143316059
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Apr 20141403235
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Jan 2015643326
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Apr 20151902615
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Aug 2015431814
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Total 2016928709242
Jan 201711718
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Total 2017189685128
Jan 2018185112
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Apr 20183584
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Total 2018143603119
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Mar 2019192012
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Total 2019179461107
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Feb 2020103912
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Aug 2020325817
Sep 2020236916
Oct 2020136924
Nov 2020206316
Dec 2020236117
Total 2020195604161
Jan 202113349
Total 202113349
Total1129548102802
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The Journal of Neuroscience: 33 (21)
Journal of Neuroscience
Vol. 33, Issue 21
22 May 2013
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A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration
Johannes Gräff, Martin Kahn, Alireza Samiei, Jun Gao, Kristie T. Ota, Damien Rei, Li-Huei Tsai
Journal of Neuroscience 22 May 2013, 33 (21) 8951-8960; DOI: 10.1523/JNEUROSCI.5657-12.2013

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A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration
Johannes Gräff, Martin Kahn, Alireza Samiei, Jun Gao, Kristie T. Ota, Damien Rei, Li-Huei Tsai
Journal of Neuroscience 22 May 2013, 33 (21) 8951-8960; DOI: 10.1523/JNEUROSCI.5657-12.2013
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  • Caloric Restriction Benefits Related to ADRCs?
    Ray Xerri
    Published on: 28 May 2013
  • Published on: (28 May 2013)
    Caloric Restriction Benefits Related to ADRCs?
    • Ray Xerri, Investor - Blogger

    I'm neither a biologist or a scientist. However, I am very familiar with much of the work done on SIRT1 through an investment I had in Sirtris Pharmacueticals and the theory that the calorie restriction diet (CRD) can activate SIRT1 and prolong life. Here is an article I wrote about the company back in 2007: http://wallstreettitan.blogspot.com/2007/12/genesis- of-age-of-life-extention.html

    More recently my inter...

    Show More

    I'm neither a biologist or a scientist. However, I am very familiar with much of the work done on SIRT1 through an investment I had in Sirtris Pharmacueticals and the theory that the calorie restriction diet (CRD) can activate SIRT1 and prolong life. Here is an article I wrote about the company back in 2007: http://wallstreettitan.blogspot.com/2007/12/genesis- of-age-of-life-extention.html

    More recently my interest has been piqued by the potential of adipose derived regenerative cells (ADRCs). Again, my interest is related to investing but I also am certainly enthralled by the science. As I said I'm not an expert in any of this. However, an interesting thought occurred to me. Might there be a connection between the CRD and ADRCs? I'll explain my thinking and ask the experts to comment.

    We now know that fat is the richest repository of stem cells in the body and that ADRCs represent a mixture of many types of regenerative cells that have shown strong evidence of therapeutic value. So what happens to all these beneficial cells when an animal is put on the CRD? Can it be that CRD causes ADRCs to be released into the bloodstream to circulate and target the first sign of trouble? Could this be a defense mechanism that releases ADRCs from fat as fat cells shrink to almost nothing or disappear? If so, do these cells roam around in the bloodstream and rejuvenate mature aging cells throughout the body? Could this be an additional mechanism that helps explain the benefits seen from the calorie restriction diet?

    The way I look at it, the questions that the experts need to answer are:

    1) Do all the ADRCs hidden in fat exist from conception or are they produced over a life time?

    2)What happens when the home of the ADRCs starts to disappear. Do the ADRCs disappear too or are they released into the body, honing in on places where they can help?

    Again, I have no peer reviewed research or technical knowledge to back this train of thought but I was intrigued enough by the idea to put it out there for those who have the resources and expertise to examine it.

    Show Less
    Competing Interests: None declared.

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