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Identification of Longevity-associated Genes in Long-lived Snell and Ames Dwarf Mice

Overview
Journal Age (Dordr)
Publisher Springer
Specialty Geriatrics
Date 2009 Nov 28
PMID 19943135
Citations 20
Authors
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Abstract

Recent landmark molecular genetic studies have identified an evolutionarily conserved insulin/IGF-1 signal transduction pathway that regulates lifespan. In C. elegans, Drosophila, and rodents, attenuated insulin/IGF-1 signaling appears to regulate lifespan and enhance resistance to environmental stress. The Ames (Prop1 (df/df)) and Snell (Pit1 (dw/dw)) hypopituitary dwarf mice with growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin deficiencies live 40-60% longer than control mice. Both mutants are resistant to multiple forms of environmental stress in vitro. Taken collectively, these genetic models indicate that diminished insulin/IGF-l signaling may play a central role in the determination of mammalian lifespan by conferring resistance to exogenous and endogenous stressors. These pleiotropic endocrine pathways control diverse programs of gene expression that appear to orchestrate the development of a biological phenotype that promotes longevity. With the ability to investigate thousands of genes simultaneously, several microarray surveys have identified potential longevity assurance genes and provided information on the mechanism(s) by which the dwarf genotypes (dw/dw) and (df/df), and caloric restriction may lead to longevity. We propose that a comparison of specific changes in gene expression shared between Snell and Ames dwarf mice may provide a deeper understanding of the transcriptional mechanisms of longevity determination. Furthermore, we propose that a comparison of the physiological consequences of the Pit1dw and Prop1df mutations may reveal transcriptional profiles similar to those reported for the C. elegans and Drosophila mutants. In this study we have identified classes of genes whose expression is similarly affected in both Snell and Ames dwarf mice. Our comparative microarray data suggest that specific detoxification enzymes of the P(450) (CYP) family as well as oxidative and steroid metabolism may play a key role in longevity assurance of the Snell and Ames dwarf mouse mutants. We propose that the altered expression of these genes defines a biochemical phenotype which may promote longevity in Snell and Ames dwarf mice.

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References
1.
Janmohamed A, Hernandez D, Phillips I, Shephard E . Cell-, tissue-, sex- and developmental stage-specific expression of mouse flavin-containing monooxygenases (Fmos). Biochem Pharmacol. 2004; 68(1):73-83. DOI: 10.1016/j.bcp.2004.02.036. View

2.
Corcos L, Fautrel A, Guillouzo A . Interleukin-1 beta antagonizes phenobarbital induction of several major cytochromes P450 in adult rat hepatocytes in primary culture. FEBS Lett. 1995; 366(2-3):159-64. DOI: 10.1016/0014-5793(95)00513-9. View

3.
Marc N, Galisteo M, Lagadic-Gossmann D, Fautrel A, Joannard F, Guillouzo A . Regulation of phenobarbital induction of the cytochrome P450 2b9/10 genes in primary mouse hepatocyte culture. Involvement of calcium- and cAMP-dependent pathways. Eur J Biochem. 2000; 267(4):963-70. DOI: 10.1046/j.1432-1327.2000.01083.x. View

4.
Dulos J, van der Vleuten M, Kavelaars A, Heijnen C, Boots A . CYP7B expression and activity in fibroblast-like synoviocytes from patients with rheumatoid arthritis: regulation by proinflammatory cytokines. Arthritis Rheum. 2005; 52(3):770-8. DOI: 10.1002/art.20950. View

5.
Krueger S, Williams D . Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism. Pharmacol Ther. 2005; 106(3):357-87. PMC: 1828602. DOI: 10.1016/j.pharmthera.2005.01.001. View