Universität zu Köln

Patti, Gary J., Tautenhahn, Ralf, Johannsen, Darcy, Kalisiak, Ewa, Ravussin, Eric ORCID: 0000-0003-2129-547X, Bruening, Jens C., Dillin, Andrew and Siuzdak, Gary ORCID: 0000-0002-4749-0014 (2014). Meta-analysis of global metabolomic data identifies metabolites associated with life-span extension. Metabolomics, 10 (4). S. 737 - 744. NEW YORK: SPRINGER. ISSN 1573-3890

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Abstract

The manipulation of distinct signaling pathways and transcription factors has been shown to influence life span in a cell-non-autonomous manner in multicellular model organisms such as Caenorhabditis elegans. These data suggest that coordination of whole-organism aging involves endocrine signaling, however, the molecular identities of such signals have not yet been determined and their potential relevance in humans is unknown. Here we describe a novel metabolomic approach to identify molecules directly associated with extended life span in C. elegans that represent candidate compounds for age-related endocrine signals. To identify metabolic perturbations directly linked to longevity, we developed metabolomic software for meta-analysis that enabled intelligent comparisons of multiple different mutants. Simple pairwise comparisons of long-lived glp-1, daf-2, and isp-1 mutants to their respective controls resulted in more than 11,000 dysregulated metabolite features of statistical significance. By using meta-analysis, we were able to reduce this number to six compounds most likely to be associated with life-span extension. Mass spectrometry-based imaging studies suggested that these metabolites might be localized to C. elegans muscle. We extended the metabolomic analysis to humans by comparing quadricep muscle tissue from young and old individuals and found that two of the same compounds associated with longevity in worms were also altered in human muscle with age. These findings provide candidate compounds that may serve as age-related endocrine signals and implicate muscle as a potential tissue regulating their levels in humans.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Patti, Gary J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tautenhahn, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Johannsen, Darcy UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalisiak, Ewa UNSPECIFIED UNSPECIFIED UNSPECIFIED Ravussin, Eric UNSPECIFIED orcid.org/0000-0003-2129-547X UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dillin, Andrew UNSPECIFIED UNSPECIFIED UNSPECIFIED Siuzdak, Gary UNSPECIFIED orcid.org/0000-0002-4749-0014 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-432444
DOI:	10.1007/s11306-013-0608-8
Journal or Publication Title:	Metabolomics
Volume:	10
Number:	4
Page Range:	S. 737 - 744
Date:	2014
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1573-3890
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INITIATOR MASS-SPECTROMETRY; CAENORHABDITIS-ELEGANS; C-ELEGANS; ENDOCRINE REGULATION; ELECTRON-TRANSPORT; DAUER FORMATION; DROSOPHILA; LONGEVITY; LIGANDS; BRAIN Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43244