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Delayed and accelerated aging share common longevity assurance mechanisms

Schumacher, B and Van Der Pluijm, I and Moorhouse, MJ and Kosteas, T and Robinson, AR and Suh, Y and Breit, TM and Van Steeg, H and Niedernhofer, LJ and Van Ijcken, W and Bartke, A and Spindler, SR and Hoeijmakers, JHJ and Van Der Hors, GTJ and Garinis, GA (2008) Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genetics, 4 (8). ISSN 1553-7390

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Abstract

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan. Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice. Subsequent analysis of significantly over-represented biological processes revealed suppression of the endocrine and energy pathways with increased stress responses in both delayed and premature aging. To test the relevance of these processes in natural aging, we compared the transcriptomes of liver, lung, kidney, and spleen over the entire murine adult lifespan and subsequently confirmed these findings on an independent aging cohort. The majority of genes showed similar expression changes in all four organs, indicating a systemic transcriptional response with aging. This systemic response included the same biological processes that are triggered in progeroid and long-lived mice. However, on a genome-wide scale, transcriptomes of naturally aged mice showed a strong association to progeroid but not to long-lived mice. Thus, endocrine and metabolic changes are indicative of "survival" responses to genotoxic stress or starvation, whereas genome-wide associations in gene expression with natural aging are indicative of biological age, which may thus delineate pro- and anti-aging effects of treatments aimed at health-span extension. © 2008 Schumacher et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Schumacher, B
Van Der Pluijm, I
Moorhouse, MJ
Kosteas, T
Robinson, AR
Suh, Y
Breit, TM
Van Steeg, H
Niedernhofer, LJ
Van Ijcken, W
Bartke, A
Spindler, SR
Hoeijmakers, JHJ
Van Der Hors, GTJ
Garinis, GA
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorKim, Stuart K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 1 August 2008
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 4
Number: 8
DOI or Unique Handle: 10.1371/journal.pgen.1000161
Schools and Programs: School of Medicine > Biochemistry and Molecular Genetics
Refereed: Yes
ISSN: 1553-7390
PubMed ID: 18704162
Date Deposited: 18 Jul 2012 20:25
Last Modified: 03 Feb 2019 06:55
URI: http://d-scholarship.pitt.edu/id/eprint/12983

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