CA2381777A1 - Identification of genetic markers of biological age and metabolism - Google Patents
Identification of genetic markers of biological age and metabolism Download PDFInfo
- Publication number
- CA2381777A1 CA2381777A1 CA002381777A CA2381777A CA2381777A1 CA 2381777 A1 CA2381777 A1 CA 2381777A1 CA 002381777 A CA002381777 A CA 002381777A CA 2381777 A CA2381777 A CA 2381777A CA 2381777 A1 CA2381777 A1 CA 2381777A1
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- tissue
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- gene expression
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6809—Methods for determination or identification of nucleic acids involving differential detection
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
Abstract
A method of measuring the biological age of a multicellular organism is disclosed. In one embodiment this method comprises the steps of obtaining a sample of nucleic acid isolated from the organism's organ, tissue or cell and determining the expression pattern of a panel of sequences within the nucleic acid that have been predetermined by either increase or decrease in response to biological aging of the organ, tissue or cell. A method of obtaining biomarkers of aging is also disclosed. This method comprises the step of comparing a gene expression profile of a young multicellular organism subject's organ, tissue or cells; a gene expression profile from a chronologically aged subject's organ, tissue or cell; and a gene expression profile from a chronologically aged but biologically younger subject's organ, tissue or cell and identifying gene expression alterations that are observed when comparing the young subjects and the chronologically aged subjects and are not observed or reduced in magnitude when comparing the young subject and the chronologically aged but biologically younger subjects.
Claims (28)
1. A method of measuring the biological age of a multicellular organism comprising the steps of:
(a) obtaining a sample of nucleic acid isolated from the organism's organ, tissue or cell, wherein the nucleic acid is RNA or a cDNA
copy of RNA and (b) determining the gene expression pattern of a panel of specific sequences within the nucleic acid pool described in (a) that have been predetermined to either increase or decrease in response to biological aging of the organ, tissue or cell, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences.
(a) obtaining a sample of nucleic acid isolated from the organism's organ, tissue or cell, wherein the nucleic acid is RNA or a cDNA
copy of RNA and (b) determining the gene expression pattern of a panel of specific sequences within the nucleic acid pool described in (a) that have been predetermined to either increase or decrease in response to biological aging of the organ, tissue or cell, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences.
2. The method of claim 1 wherein the expression patterns of at least ten sequences are determined in step (b).
3. The method of claim 2 wherein the expression patterns of at least 20 sequences are determined in step (b).
4. The method of claim 3 wherein the expression levels of at least 30 sequences are determined in step (b).
5. The method of claim 4 wherein the expression levels of at least 40 sequences are determined in step (b).
6. The method of claim 5 wherein the expression levels of at least 50 sequences are determined in step (b).
7. The method of claim 1 wherein the organism is a mammal.
8. The method of claim 7 wherein the mammal is slected from the group consisting of humans, rats and mice.
9. The method of claim 1 wherein the nucleic acid is isolated from a tissue selected from the group consisting of brain tissue, heart tissue, muscle tissue, skin, liver tissue, blood, skeletal muscle, lymphocytes and mucosa.
10. The method of obtaining biomarkers of aging comprising the steps of:
(a) comparing a gene expression profile of a young multicellular organism subject's organ, tissue or cells; a gene expression profile from a biologically and chronologically aged subject's organ, tissue or cell; and a gene expression profile from a chronologically aged but biologically younger subject's organ, tissue or cell, and (b) identifying gene expression alterations that are observed when comparing the young subjects and the chronologically and biologically aged subjects and are not observed or reduced in magnitude when comparing the young subjects and chronologically aged but biologically younger subjects.
(a) comparing a gene expression profile of a young multicellular organism subject's organ, tissue or cells; a gene expression profile from a biologically and chronologically aged subject's organ, tissue or cell; and a gene expression profile from a chronologically aged but biologically younger subject's organ, tissue or cell, and (b) identifying gene expression alterations that are observed when comparing the young subjects and the chronologically and biologically aged subjects and are not observed or reduced in magnitude when comparing the young subjects and chronologically aged but biologically younger subjects.
11. The method of claim 10 wherein one uses high density oligonucleotide arrays comprising at least 5-10% of the subject's genes to compare the subjects gene expression profile.
12. The method of claim 10 wherein the gene expression profile indicates a two-fold or greater increase or decrease in the expression of certain genes in chronologically aged subjects.
13. The method of claim 10 wherein the gene expression profile indicated a 3-fold or greater increase or decrease in the expression of certain genes in chronologically aged subjects.
14. The method of claim 10 wherein the gene expression profile indicates a 4-fold or greater increase or decrease in the expression of certain genes in chronologically aged subjects.
15. A method of measuring biological age of muscle tissue comprising the step of quantifying the mRNA abundance of a panel of biomarkers selected from the group consisting of markers W08057, AA114576, 11071777, 11106112, D29016, and M16465.
16. A method of measuring biological age of muscle tissue comprising the step of quantifying the mRNA abundance of a panel of biomarkers selected from the group consisting of markers described in Tables 1, 2, 15, and 16.
17. A method of measuring biological age of brain tissue comprising the step of quantifying the mRNA abundance of a panel of biomarkers selected from the group consisting of markers M17440, K01347, AA116604 and X16995.
18. The method of claim 10 wherein the subject is a mammal.
19. The method of claim 18 wherein the mammal is selected from the group consisting of humans, mice and rats.
20. A method of measuring biological age of brain tissue comprising the step of quantifying the mRNA abundance of a panel of biomarkers selected from the group consisting of markers described in Tables 5, 6, 9, and 10.
21. A method of measuring biological age of heart tissue comprising the step of quantifying the mRNA abundance of a panel of biomarkers selected from the group consisting of markers described in Tables 11, 12, 13 and 14.
22. A method for screening a compound for the ability to inhibit or retard the aging process in multicellular organisms tissue, organ or cell comprising the steps of:
(a) dividing test organisms into first and second mammalian samples;
(b) exposing the organisms of the first sample to a test compound;
(c) analyzing tissues, organs or cells of the first and second samples for the level of expression of a panel of sequences that have been predetermined to either increase or decrease in response to biological aging of the tissue;
(d) comparing the analysis of the first and second samples and identifying test compounds that modify the expression of the sequences of step (c) in the first sample such that the expression pattern is indicative of tissue, organ or cell that has an inhibited or retarded biological age.
(a) dividing test organisms into first and second mammalian samples;
(b) exposing the organisms of the first sample to a test compound;
(c) analyzing tissues, organs or cells of the first and second samples for the level of expression of a panel of sequences that have been predetermined to either increase or decrease in response to biological aging of the tissue;
(d) comparing the analysis of the first and second samples and identifying test compounds that modify the expression of the sequences of step (c) in the first sample such that the expression pattern is indicative of tissue, organ or cell that has an inhibited or retarded biological age.
23. A method as in claim 22, wherein the organism is a mammal.
24. The method of claim 23, wherein the mammal is selected from the group consisting of humans, rats and mice.
25. A method as in claim 23, wherein the tissue is selected from the group consisting of brain tissue, heart tissue, muscle tissue, blood, skeletal muscle, mucosa, skin, lymphocytes and liver tissue.
26. A method of detecting whether a test compound mimics the gene profile induced by caloric restriction, comprising the steps of:
(a) exposing a multicellular organism to the test compound, and (b) measuring the expression level of a panel of sequences predetermined to either increase or decrease in response to biological aging in a tissue, organ or cell of the organism and comparing the measurement to a measurement obtained in the same tissue, organ or cell in calorically restricted subjects.
(a) exposing a multicellular organism to the test compound, and (b) measuring the expression level of a panel of sequences predetermined to either increase or decrease in response to biological aging in a tissue, organ or cell of the organism and comparing the measurement to a measurement obtained in the same tissue, organ or cell in calorically restricted subjects.
27. The method of claim 26 wherein the multicellular organism is a mammal.
28. The method of claim 27 wherein the mammal is selected from the group consisting of humans, rodents and mice.
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14854099P | 1999-08-12 | 1999-08-12 | |
US60/148,540 | 1999-08-12 | ||
US17823200P | 2000-01-26 | 2000-01-26 | |
US60/178,232 | 2000-01-26 | ||
US21192300P | 2000-06-16 | 2000-06-16 | |
US60/211,923 | 2000-06-16 | ||
PCT/US2000/021603 WO2001012851A2 (en) | 1999-08-12 | 2000-08-08 | Identification of genetic markers of biological age and metabolism |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2381777A1 true CA2381777A1 (en) | 2001-02-22 |
CA2381777C CA2381777C (en) | 2011-10-04 |
Family
ID=27386702
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2381777A Expired - Lifetime CA2381777C (en) | 1999-08-12 | 2000-08-08 | Identification of genetic markers of biological age and metabolism |
Country Status (7)
Country | Link |
---|---|
US (3) | US6569624B1 (en) |
EP (1) | EP1200629B1 (en) |
AT (1) | ATE384137T1 (en) |
AU (1) | AU782102B2 (en) |
CA (1) | CA2381777C (en) |
DE (1) | DE60037817D1 (en) |
WO (1) | WO2001012851A2 (en) |
Families Citing this family (47)
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US7452664B2 (en) | 1999-12-15 | 2008-11-18 | Massachusetts Institute Of Technology | Methods for identifying agents which alter histone protein acetylation |
US8642284B1 (en) | 1999-12-15 | 2014-02-04 | Massachusetts Institute Of Technology | Methods for identifying agents that alter NAD-dependent deacetylation activity of a SIR2 protein |
US6406853B1 (en) | 1999-12-23 | 2002-06-18 | The Regents Of The University Of California | Interventions to mimic the effects of calorie restriction |
WO2001045752A1 (en) * | 1999-12-23 | 2001-06-28 | The Regents Of The University Of California | Interventions to mimic the effects of calorie restriction |
EP1399553A2 (en) | 2000-12-12 | 2004-03-24 | The University of Connecticut | Polynucleotides encoding cellular transporters and methods of use therof |
US7572575B2 (en) | 2000-12-13 | 2009-08-11 | Massachusetts Institute Of Technology | SIR2 activity |
WO2002074911A2 (en) * | 2001-03-19 | 2002-09-26 | Wisconsin Alumni Research Foundation | Identification of gene expression alterations underlying the aging process in mammals |
US20030190312A1 (en) * | 2001-06-22 | 2003-10-09 | The Regents Of The University Of California | Eukaryotic genes involved in adult lifespan regulation |
US20030036079A1 (en) * | 2001-06-26 | 2003-02-20 | Weindruch Richard H. | Gene expression alterations underlying the retardation of aging by caloric restriction in mammals |
AU2002313737A1 (en) * | 2001-08-13 | 2003-04-01 | University Of Kentucky Research Foundation | Gene expression profile biomarkers and therapeutic targets for brain aging and age-related cognitive impairment |
US20030082597A1 (en) * | 2001-08-15 | 2003-05-01 | Cannon L. Edward | Age-associated markers |
CN102402650A (en) | 2001-11-09 | 2012-04-04 | 生命技术公司 | Identification, monitoring and treatment of disease and characterization of biological condition using gene expression profiles |
WO2003099781A2 (en) * | 2002-05-24 | 2003-12-04 | Boehringer Ingelheim Pharmaceuticals, Inc. | METHODS FOR THE IDENTIFICATION OF IKKα FUNCTION AND OTHER GENES USEFUL FOR TREATMENT OF INFLAMMATORY DISEASES |
AU2003256408A1 (en) * | 2002-08-09 | 2004-02-25 | The Regents Of The University Of California | Eukaryotic genes involved in adult lifespan regulation |
FR2847269B1 (en) * | 2002-11-19 | 2006-07-28 | Coletica | METHOD FOR IDENTIFYING AN EVENTUAL MODIFICATION OF AT LEAST ONE BIOLOGICAL PARAMETER USING YOUNG AND AGE LIVING CELLS |
WO2004047728A2 (en) * | 2002-11-26 | 2004-06-10 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
US20040191775A1 (en) * | 2003-03-12 | 2004-09-30 | Spindler Stephen R. | Methods of analyzing genes affected by caloric restriction or caloric restriction mimetics |
US20050123451A1 (en) * | 2003-10-31 | 2005-06-09 | Hiroshi Nomura | System and apparatus for body fluid analysis using surface-textured optical materials |
US20070275108A1 (en) * | 2003-12-19 | 2007-11-29 | Geesamen Bard J | Life Span Managment |
US20050266438A1 (en) * | 2004-03-16 | 2005-12-01 | The Regents Of The University Of California | Genetic networks regulated by attenuated GH/IGF1 signaling and caloric restriction |
US20050228237A1 (en) * | 2004-04-12 | 2005-10-13 | Frank Shallenberger | Method for analyzing the biological age of a subject |
US7273453B2 (en) * | 2004-04-12 | 2007-09-25 | Frank Shallenberger | Method for analyzing the biological age of a subject |
WO2005123955A2 (en) * | 2004-06-09 | 2005-12-29 | Children's Medical Center Corporation | Methods and compositions for modifying gene regulation and dna damage in ageing |
CN101137417B (en) * | 2005-02-15 | 2012-05-30 | 有限会社日本通商 | Physical strength age measuring system |
US20070099830A1 (en) | 2005-04-21 | 2007-05-03 | Massachusetts Institute Of Technology | Sirt4 activities |
US7960605B2 (en) | 2006-03-17 | 2011-06-14 | BioMaker Pharmaceuticals, Inc. | Methods for testing for caloric restriction (CR) mimetics |
EP2428587A3 (en) * | 2006-10-13 | 2012-07-18 | Metabolon Inc. | Biomarkers related to metabolic age and methods using the same |
EP2128275A4 (en) * | 2007-02-23 | 2010-12-08 | Progenika Biopharma Sa | Method and product for "in vitro" genotyping with applications in anti-ageing medicine |
US8420088B2 (en) | 2008-01-28 | 2013-04-16 | Novartis Ag | Methods and compositions using FGF23 fusion polypeptides |
US7666137B2 (en) * | 2008-04-10 | 2010-02-23 | Frank Shallenberger | Method for analyzing mitochondrial function |
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EP2331707A4 (en) * | 2008-08-28 | 2012-06-06 | Dermtech Int | Determining age ranges of skin samples |
WO2010104573A1 (en) * | 2009-03-11 | 2010-09-16 | Nestec S.A. | Tissue-specific aging biomarkers |
US20110091081A1 (en) * | 2009-10-16 | 2011-04-21 | General Electric Company | Method and system for analyzing the expression of biomarkers in cells in situ in their tissue of origin |
US8320655B2 (en) * | 2009-10-16 | 2012-11-27 | General Electric Company | Process and system for analyzing the expression of biomarkers in cells |
US8824769B2 (en) * | 2009-10-16 | 2014-09-02 | General Electric Company | Process and system for analyzing the expression of biomarkers in a cell |
CA2779606A1 (en) * | 2009-11-10 | 2011-05-19 | Nestec S.A. | Heart aging biomarkers and methods of use |
CN106511415A (en) | 2010-05-24 | 2017-03-22 | Nse产品公司 | Oral formulations for counteracting effects of aging |
WO2013027191A1 (en) | 2011-08-25 | 2013-02-28 | Novartis Ag | Methods and compositions using fgf23 fusion polypeptides |
US8652518B2 (en) | 2012-04-15 | 2014-02-18 | Jahahreeh Finley | Compositions and methods for the prevention and treatment of diseases or conditions associated with oxidative stress, inflammation, and metabolic dysregulation |
FR2993282B1 (en) * | 2012-07-13 | 2017-11-10 | Expanscience Lab | METHOD FOR IDENTIFYING MOLECULAR MARKERS OF CHILD'S SKIN |
US20190093163A1 (en) * | 2015-06-12 | 2019-03-28 | President And Fellows Of Harvard College | Compositions and methods for maintaining splicing fidelity |
WO2019074615A2 (en) * | 2017-09-14 | 2019-04-18 | OneSkin Technologies, Inc. | In vitro methods for skin therapeutic compound discovery using skin age biomarkers |
WO2020198229A1 (en) | 2019-03-26 | 2020-10-01 | Dermtech, Inc. | Novel gene classifiers and uses thereof in skin cancers |
US11227691B2 (en) | 2019-09-03 | 2022-01-18 | Kpn Innovations, Llc | Systems and methods for selecting an intervention based on effective age |
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US5744300A (en) | 1993-03-24 | 1998-04-28 | Geron Corporation | Methods and reagents for the identification and regulation of senescence-related genes |
US6087102A (en) * | 1998-01-07 | 2000-07-11 | Clontech Laboratories, Inc. | Polymeric arrays and methods for their use in binding assays |
US6406853B1 (en) | 1999-12-23 | 2002-06-18 | The Regents Of The University Of California | Interventions to mimic the effects of calorie restriction |
-
2000
- 2000-08-08 DE DE60037817T patent/DE60037817D1/en not_active Expired - Lifetime
- 2000-08-08 CA CA2381777A patent/CA2381777C/en not_active Expired - Lifetime
- 2000-08-08 EP EP00952626A patent/EP1200629B1/en not_active Expired - Lifetime
- 2000-08-08 US US09/630,567 patent/US6569624B1/en not_active Expired - Lifetime
- 2000-08-08 WO PCT/US2000/021603 patent/WO2001012851A2/en active IP Right Grant
- 2000-08-08 AU AU65289/00A patent/AU782102B2/en not_active Expired
- 2000-08-08 AT AT00952626T patent/ATE384137T1/en not_active IP Right Cessation
-
2002
- 2002-12-02 US US10/307,706 patent/US20030157526A1/en not_active Abandoned
-
2006
- 2006-11-20 US US11/974,837 patent/US20080254464A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
WO2001012851A3 (en) | 2001-08-23 |
WO2001012851A2 (en) | 2001-02-22 |
US20030157526A1 (en) | 2003-08-21 |
EP1200629B1 (en) | 2008-01-16 |
AU782102B2 (en) | 2005-07-07 |
DE60037817D1 (en) | 2008-03-06 |
US6569624B1 (en) | 2003-05-27 |
AU6528900A (en) | 2001-03-13 |
EP1200629A2 (en) | 2002-05-02 |
CA2381777C (en) | 2011-10-04 |
US20080254464A1 (en) | 2008-10-16 |
ATE384137T1 (en) | 2008-02-15 |
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Legal Events
Date | Code | Title | Description |
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EEER | Examination request | ||
MKEX | Expiry |
Effective date: 20200810 |