BIOMARKERS OF SIRTUIN ACTIVITY AND METHODS OF USE THEREOF
First Claim
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1. A method of detecting sirtuin modulation in a subject comprising determining the expression level of at least one sirtuin biomarker in a biological sample from the subject, wherein a change in the expression level of the sirtuin biomarker as compared to a control is indicative of sirtuin modulation.
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Abstract
Provided are methods for monitoring sirtuin modulation in a subject, for example, during therapeutic treatment with a sirtuin modulating compound. The methods involve determining the expression level of one or more sirtuin biomarkers in a biological sample from the subject. Also provided are methods for identifying compounds that modulate the activity of a sirtuin protein using one or more sirtuin biomarkers.
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Citations
74 Claims
- 1. A method of detecting sirtuin modulation in a subject comprising determining the expression level of at least one sirtuin biomarker in a biological sample from the subject, wherein a change in the expression level of the sirtuin biomarker as compared to a control is indicative of sirtuin modulation.
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2. (canceled)
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4-6. -6. (canceled)
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10-12. -12. (canceled)
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14-17. -17. (canceled)
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18. A method for monitoring therapeutic treatment with a sirtuin modulator comprising determining the expression level of at least one sirtuin biomarker in a biological sample from a subject being treated with a sirtuin modulator.
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19-36. -36. (canceled)
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37. A method for monitoring the progress of therapeutic treatment with a sirtuin modulator, comprising:
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a) administering a sirtuin modulator to a subject, b) obtaining a biological sample from said subject, and c) determining the expression level of at least one sirtuin biomarker in the biological sample; wherein an altered expression level of the sirtuin biomarker in the biological sample as compared to a control is indicative of therapeutic sirtuin modulation in said subject.
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38-42. -42. (canceled)
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43. A method for identifying a subject that would benefit from treatment with a sirtuin modulating compound, comprising determining the expression level of at least one sirtuin biomarker in a biological sample from the subject, wherein an altered expression level of the sirtuin biomarker as compared to a control is indicative of a subject that would benefit from treatment with a sirtuin modulating compound.
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44-48. -48. (canceled)
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49. A method for evaluating a subject'"'"'s risk of developing a sirtuin-mediated disease or disorder, comprising determining the expression level of at least one sirtuin biomarker in a biological sample from the subject, wherein an altered expression level of the sirtuin biomarker as compared to a control is indicative of a subject at risk for developing a sirtuin-mediated disease or disorder.
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50-52. -52. (canceled)
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53. A method for identifying a compound that modulates sirtuin activity, comprising:
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a) contacting a cell expressing a sirtuin protein with a test compound, and b) determining the expression level of at least one sirtuin biomarker in the cell, wherein a change in the expression level of the sirtuin biomarker in the presence of the test compound as compared to a control is indicative of a compound that modulates sirtuin activity.
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54-56. -56. (canceled)
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57. A method for treating a sirtuin-mediated disease or disorder in a subject, comprising:
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a) administering a sirtuin modulating compound to the subject, and b) monitoring the expression level of at least one sirtuin biomarker over time to determine whether the course of treatment in the subject should be modified.
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58-61. -61. (canceled)
- 62. A kit for detecting the expression level of a sirtuin biomarker, comprising at least one component for determining the expression level of a sirtuin biomarker and at least one sirtuin modulating compound.
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66. A method of determining the level of sirtuin activity in a biological sample comprising determining the expression level of at least one sirtuin biomarker in the biological sample.
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67. A method of detecting sirtuin modulation in a subject comprising determining the expression level of FGF21 in a biological sample from the subject, wherein a change in the expression level of FGF21 as compared to a control is indicative of sirtuin modulation.
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68. A method for monitoring therapeutic treatment with a sirtuin modulator comprising determining the expression level of FGF21 in a biological sample from a subject being treated with a sirtuin modulator, wherein a change in the expression level of FGF21 upon treatment with the sirtuin modulator is indicative of therapeutic sirtuin modulation in the subject.
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69. A method for monitoring the progress of therapeutic treatment with a sirtuin modulator, comprising:
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a) administering a sirtuin modulator to a subject, b) obtaining a biological sample from said subject, and c) determining the expression level of FGF21 in the biological sample; wherein an altered expression level of FGF21 in the biological sample as compared to a control is indicative of therapeutic sirtuin modulation in said subject.
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70. A method for identifying a subject that would benefit from treatment with a sirtuin modulating compound, comprising determining the expression level of FGF21 in a biological sample from the subject, wherein an altered expression level of FGF21 as compared to a control is indicative of a subject that would benefit from treatment with a sirtuin modulating compound.
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71. A method for evaluating a subject'"'"'s risk of developing a sirtuin-mediated disease or disorder, comprising determining the expression level of FGF21 in a biological sample from the subject, wherein an altered expression level of FGF21 as compared to a control is indicative of a subject at risk for developing a sirtuin-mediated disease or disorder.
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72. A method for identifying a compound that modulates sirtuin activity, comprising:
a) contacting a cell expressing a sirtuin protein with a test compound, and b) determining the expression level of FGF21 in the cell, wherein a change in the expression level of FGF21 in the presence of the test compound as compared to a control is indicative of a compound that modulates sirtuin activity.
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73. A method for treating a sirtuin-mediated disease or disorder in a subject, comprising:
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a) administering a sirtuin modulating compound to the subject, and b) monitoring the expression level of FGF21 over time to determine whether the course of treatment in the subject should be modified.
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74-86. -86. (canceled)
Specification