Delayed and accelerated aging share common longevity assurance mechanisms

Björn Schumacher, Ingrid Van Der Pluijm, Michael J. Moorhouse, Theodore Kosteas, Andria Rasile Robinson, Yousin Suh, Timo M. Breit, Harry Van Steeg, Laura J. Niedernhofer, Wilfred Van Ijcken, Andrzej Bartke, Stephen R. Spindler, Jan H J Hoeijmakers, Gijsbertus T J Van Der Hors, George A. Garinis

Research output: Contribution to journalArticle

115 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1000161
JournalPLoS Genetics
Volume4
Issue number8
DOIs
StatePublished - Aug 2008
Externally publishedYes

Fingerprint

mice
Genome
genome
Biological Phenomena
Transcriptome
transcriptome
stress response
biological processes
anti-aging properties
DNA Repair-Deficiency Disorders
Premature Aging
liver
Liver
DNA repair
Starvation
DNA Damage
starvation
spleen
repair
gene expression

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Schumacher, B., Van Der Pluijm, I., Moorhouse, M. J., Kosteas, T., Robinson, A. R., Suh, Y., ... Garinis, G. A. (2008). Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genetics, 4(8), [e1000161]. https://doi.org/10.1371/journal.pgen.1000161

Delayed and accelerated aging share common longevity assurance mechanisms. / Schumacher, Björn; Van Der Pluijm, Ingrid; Moorhouse, Michael J.; Kosteas, Theodore; Robinson, Andria Rasile; Suh, Yousin; Breit, Timo M.; Van Steeg, Harry; Niedernhofer, Laura J.; Van Ijcken, Wilfred; Bartke, Andrzej; Spindler, Stephen R.; Hoeijmakers, Jan H J; Van Der Hors, Gijsbertus T J; Garinis, George A.

In: PLoS Genetics, Vol. 4, No. 8, e1000161, 08.2008.

Research output: Contribution to journalArticle

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 2008, 'Delayed and accelerated aging share common longevity assurance mechanisms', PLoS Genetics, vol. 4, no. 8, e1000161. https://doi.org/10.1371/journal.pgen.1000161
Schumacher B, Van Der Pluijm I, Moorhouse MJ, Kosteas T, Robinson AR, Suh Y et al. Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genetics. 2008 Aug;4(8). e1000161. https://doi.org/10.1371/journal.pgen.1000161
Schumacher, Björn ; Van Der Pluijm, Ingrid ; Moorhouse, Michael J. ; Kosteas, Theodore ; Robinson, Andria Rasile ; Suh, Yousin ; Breit, Timo M. ; Van Steeg, Harry ; Niedernhofer, Laura J. ; Van Ijcken, Wilfred ; Bartke, Andrzej ; Spindler, Stephen R. ; Hoeijmakers, Jan H J ; Van Der Hors, Gijsbertus T J ; Garinis, George A. / Delayed and accelerated aging share common longevity assurance mechanisms. In: PLoS Genetics. 2008 ; Vol. 4, No. 8.
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