Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2006 Jun;28(2):125-44.
doi: 10.1007/s11357-006-9008-6. Epub 2006 Jun 3.

Identification of longevity-associated genes in long-lived Snell and Ames dwarf mice

W H Boylston  1 , James H DeFord, John Papaconstantinou
Affiliations

Identification of longevity-associated genes in long-lived Snell and Ames dwarf mice

W H Boylston et al. Age (Dordr). 2006 Jun.

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.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1210/me.9.9.1214', 'is_inner': False, 'url': 'https://doi.org/10.1210/me.9.9.1214'}, {'type': 'PubMed', 'value': '7491113', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/7491113/'}]}
    2. Abbaszade IG, Clarke TR, Park CH, Payne AH (1995) The mouse 3 beta-hydroxysteroid dehydrogenase multigene family includes two functionally distinct groups of proteins. Mol Endocrinol 9:1214–1222 - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/0014-5793(95)00513-9', 'is_inner': False, 'url': 'https://doi.org/10.1016/0014-5793(95)00513-9'}, {'type': 'PubMed', 'value': '7789536', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/7789536/'}]}
    2. Abdel-Razzak Z, Corcos L, Fantrel A, Guillouzo A (1995) Interleukin-1 beta antagonizes phenobarbital induction of several major cytochromes P450 in adult rat hepatocytes in primary culture. FEBS Lett 366:159–164 - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/j.bbrc.2005.05.063', 'is_inner': False, 'url': 'https://doi.org/10.1016/j.bbrc.2005.05.063'}, {'type': 'PubMed', 'value': '15925325', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/15925325/'}]}
    2. Amador-Noguez D, Zimmerman J, Venable S, Darlington G (2005) Gender-specific alterations in gene expression and loss of liver sexual dimorphism in the long-lived Ames dwarf mice. Biochem Biophys Res Commun 332:1086–2000 - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1053/jhep.2002.35276', 'is_inner': False, 'url': 'https://doi.org/10.1053/jhep.2002.35276'}, {'type': 'PubMed', 'value': '12198646', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/12198646/'}]}
    2. Anderson SP, Yoon L, Richard EB, Dunn CS, Cattley RC, Corton JC (2002) Delayed liver regeneration in peroxisomes proliferators-activated receptor-alpha-null mice. Hepatology 36:544–554 - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1210/en.2005-0411', 'is_inner': False, 'url': 'https://doi.org/10.1210/en.2005-0411'}, {'type': 'PubMed', 'value': '15919742', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/15919742/'}]}
    2. Bartke A (2005) Minireview: role of the growth hormone/insulin-like growth factor system in mammalian aging. Endocrinology 146:3718–3723 - PubMed