- Patent Number:
9,322,821
- Appl. No:
14/491609
- Application Filed:
September 19, 2014
- نبذة مختصرة :
Using NMR/MS based metabonomics and targeted lipidomics approaches the inventors have explored the metabolic phenotypes of aging and longevity in a cohort including centenarians, elderly and young adults. The invention provides biomarkers for a reduced risk of developing ageing related chronic inflammatory disorders and propose an in vitro method of diagnosing a lifestyle that allows to delay and/or avoid ageing related chronic inflammatory disorders using p-cresol sulphate as biomarker.
- Inventors:
Nestec S.A. (Vevey, CH)
- Assignees:
NESTEC S.A. (Vevey, CH)
- Claim:
1. An in vitro method of diagnosing a lifestyle that allows a subject to delay and/or avoid an ageing related chronic inflammatory disorder, comprising determining a level of p-cresol sulphate (PSC) in a urine sample obtained from the subject after a change in lifestyle has been made, and comparing the subject's PCS level to a predetermined reference value, wherein the predetermined reference value is based on a urine PCS level obtained from the subject before the change in lifestyle, wherein the subject is a human adult of at least 45 years of age, wherein the ageing related chronic inflammatory disorder is atherosclerosis, arthritis, dementia, type 2 diabetes, or osteoporosis, and wherein an elevated urine PCS level in the sample compared to the predetermined reference value indicates an increased likelihood that the lifestyle allows the subject to delay and/or avoid the ageing related chronic inflammatory disorder.
- Claim:
2. The method of claim 1 , further comprising determining a level of phenylacetylglutamine (PAG) in the sample, and comparing the subject's PAG level to a predetermined reference value, wherein the predetermined reference value is based on a urine PAG level obtained from the subject before the change in lifestyle, and wherein elevated urine PCS and PAG levels in the sample compared to the predetermined reference values indicate an increased likelihood that the change in lifestyle allows the subject to delay and/or avoid the ageing related chronic inflammatory disorder.
- Claim:
3. The method of claim 2 , wherein the level of PAG in the sample and the predetermined reference value are determined by 1H-NMR and/or mass spectrometry.
- Claim:
4. The method of claim 2 , wherein the predetermined reference value is 81 μmol/mmol creatinine for PAG in urine.
- Claim:
5. The method of claim 1 , wherein the method serves to diagnose a lifestyle that permits healthy ageing.
- Claim:
6. The method of claim 1 , wherein the method serves to diagnose longevity.
- Claim:
7. The method of claim 1 , wherein the method serves to diagnose healthier gut microflora-host interactions.
- Claim:
8. The method of claim 7 , wherein the subject is an elderly subject.
- Claim:
9. The method of claim 1 , wherein the change in lifestyle is a change in diet.
- Claim:
10. The method of claim 9 , wherein the change in diet is use of at least one nutritional product that was previously not consumed or consumed in different amounts.
- Claim:
11. The method of claim 9 , wherein the method serves to detect the effectiveness of a new nutritional regimen.
- Claim:
12. The method of claim 1 wherein the levels of PCS in the sample and the predetermined reference value are determined by 1H-NMR and/or mass spectrometry.
- Claim:
13. The method of claim 1 , wherein the predetermined reference value is 63 μmol/mmol creatinine for PCS in urine.
- Claim:
14. The method of claim 1 , wherein the method further comprises increasing diagnostic precision by determining whether a level of one or more of biomarkers selected from the group consisting 1-O-alkyl-2-acylglycerophoshocholine(PC-O) 32:1, 1-O-alkyl-2-acylglycerophosphocholine(PC-O) 34:1, 15-hydroxy-eicosatetraenoic acid (15-HpETE), leukotriene E4 (LTE4), leukotriene B4 (LTB4), and 8,9-epoxyeicosatrienoic (8,9 EpETre) is increased in serum, and/or whether a level of one or more biomarkers selected from the group consisting of hydroxy-sphingomyelin (SM-OH) 22:1, lysophosphatidylcholines (LPC) 18:0, sphingomyelin (SM) 24:0, 1-O-alkyl-2-acylglycerophosphocholine (PC-O) 34:3, 1-O-alkyl-2-acylglycerophosphocholine(PC-O) 36:4, 1-O-alkyl-2-acylglycerophosphocholine (PC-O) 40:1, phosphatidylcholine (PC) 36:2, hydroxyoctadecadienoic acid (9-HODE), 9-oxo-octadecadienoic acid (9-oxo-HODE), and 11,12-epoxyeicosatrienoic acid (11,12-DiHETre) is decreased in serum, compared to a predetermined reference value based on a serum level of the one or more biomarkers obtained from the subject before the change in lifestyle.
- Patent References Cited:
2008/0124752 May 2008 Ryals
2009/0155826 June 2009 Hu
2012/0129265 May 2012 Lundin et al.
2012/0202240 August 2012 Deigner et al.
2014/0343865 November 2014 Brown
2015/0065366 March 2015 McDunn
2015/0072043 March 2015 Collino et al.
2015/0072320 March 2015 Collino et al.
2015/0072363 March 2015 Collino et al.
2015/0105296 April 2015 Collino et al.
2249161 November 2010
2011/010104 January 2011
2011/063470 June 2011
2011/140093 November 2011
- Other References:
Biagi, E. et al., “Ageing of the human metaorganism: the microbial counterpart,” Age: Journal of the American Aging Association, 34(1):247-267, 2011. cited by applicant
Collino, S. et al., “Monitoring healthy metabolic trajectories with nutritional metabonomics,” Nutrients, 1(1): 101-110, 2009. cited by applicant
Linnane, A. et al., “Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide,” Biogerontology, 8(5):445-467, 2007. cited by applicant
Rhee, E. et al., “Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans,” Journal of Clinical Investigation, 121(4):1402-11, 2011. cited by applicant
Yap, I. et al., “Metabolome-wide association study identifies multiple biomarkers that discriminate North and South Chinese populations at differing risks of cardiovascular disease: INTERMAP Study,” Journal of Proteome Research, 9(12):6647-54, 2010. cited by applicant
Caprari, P. et al., “Aging and red blood cell membrane: a study of centenarians,” Experimental Gerontology, 34(1):47-57, 1999. cited by applicant
Feldstein, A. et al., “Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis,” Journal of Lipid Research, 51(10):3046-54, 2010. cited by applicant
Gieger, C. et al., “Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum,” PLOS Genetics, 4(11):e1000282, 12 pages, 2008. cited by applicant
Giunta, S., “Is inflammaging an auto[innate]immunity subclinical syndrome?” Immunity & Ageing, 3:12, 2006. (2 pages). cited by applicant
“Helmholtz Zentrum München, “Parameters at the Metabolic Platform of the Genome Analysis Center,” Jan. 1, 2009, German Research Centre for Environmental Health (GmbH), Metabolomic Platform, Genome Analysis Center, Institute of Experimental Genetics, Neuherberg, Germany, retrieved online from on Jun. 26, 2012, 6 pages.” cited by applicant
Romisch-Margl, W. et al., “Procedure for tissue sample preparation and metabolite extraction for high-throughput targeted metabolomics,” Metabolomics, 8(1):133-142, 2011. cited by applicant
Shearer, G. et al., “Lipoprotein lipase releases esterified oxylipins from very low-density lipoproteins,” Prostaglandis Leukotrienes and Essential Fatty Acids, 79(6):215-222, 2008. cited by applicant
Yang, J. et al., “Quantitative profiling method for oxylipin metabolome by liquid chromatography electrospray ionization tandem mass spectrometry,” Analytical Chemistery, 81(19):8085-93, 2009. cited by applicant
- Primary Examiner:
Wallenhorst, Maureen
- Attorney, Agent or Firm:
Kilpatrick Townsend & Stockton LLP
- الرقم المعرف:
edspgr.09322821
No Comments.