Delayed and Accelerated Aging Share Common Longevity Assurance Mechanisms

• DOI: 10.1371/journal.pgen.1000161
• Publication Date: 2008-08-14T21:49:07Z
• Authors: Björn Schumacher; Ingrid van der Pl...; Michael J. Moorhouse; Theodore Kosteas; Andria Rasile Rob...; Yousin Suh; Timo M. Breit; Harry van Steeg; Laura J. Niedernh...; Wilfred van IJcken; Andrzej Bartke; Stephen R. Spindler; Jan H. J. Hoeijma...; Gijsbertus T. J. ...; George A. Garinis
• Keywords: Progeria; Premature aging; Calorie Restriction; Werner syndrome; Genome-wide Association Study

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