The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Somatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity
Open accessAbstract
Growth hormone (GH) is a key determinant of postnatal growth and plays an important role in the control of metabolism and body composition. Surprisingly, deficiency in GH signaling delays aging and remarkably extends longevity in laboratory mice. In GH-deficient and GH-resistant animals, the “healthspan” is also extended with delays in cognitive decline and in the onset of age-related disease. The role of hormones homologous to insulin-like growth factor (IGF, an important mediator of GH actions) in the control of aging and lifespan is evolutionarily conserved from worms to mammals with some homologies extending to unicellular yeast. The combination of reduced GH, IGF-I, and insulin signaling likely contributes to extended longevity in GH or GH receptor-deficient organisms. Diminutive body size and reduced fecundity of GH-deficient and GH-resistant mice can be viewed as trade-offs for extended longevity. Mechanisms responsible for delayed aging of GH-related mutants include enhanced stress resistance and xenobiotic metabolism, reduced inflammation, improved insulin signaling, and various metabolic adjustments. Pathological excess of GH reduces life expectancy in men as well as in mice, and GH resistance or deficiency provides protection from major age-related diseases, including diabetes and cancer, in both species. However, there is yet no evidence of increased longevity in GH-resistant or GH-deficient humans, possibly due to non-age-related deaths. Results obtained in GH-related mutant mice provide striking examples of mutations of a single gene delaying aging, reducing age-related disease, and extending lifespan in a mammal and providing novel experimental systems for the study of mechanisms of aging.
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Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766
Kuhn, H., Dickinson-Anson, H., & Gage, F. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-06-02027.1996 · Cited by 3,139
Extending Healthy Life Span—From Yeast to Humans
Fontana, L., Partridge, L., & Longo, V. D. (2010) · Science · doi:10.1126/science.1172539 · Cited by 3,023
Self-citationIGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P. C., Cervera, P., & Le Bouc, Y. (2003) · Nature · doi:10.1038/nature01298 · Cited by 2,109
Suppression of Aging in Mice by the Hormone Klotho
Kurosu, H., Yamamoto, M., Clark, J. D., Pastor, J. V., Nandi, A., Gurnani, P., McGuinness, O. P., Chikuda, H., Yamaguchi, M., Kawaguchi, H., et al. (2005) · Science · doi:10.1126/science.1112766 · Cited by 1,935
Pleiotropy, natural selection, and the evolution of senescence
Williams, G. C. (1957) · Evolution · doi:10.2307/2406060 · Cited by 1,912
The p66shc adaptor protein controls oxidative stress response and life span in mammals
Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, P. P., Lanfrancone, L., & Pelicci, P. G. (1999) · Nature · doi:10.1038/46311 · Cited by 1,712
Giustina, A., & Veldhuis, J. D. (1998) · Endocrine Reviews · doi:10.1210/edrv.19.6.0353 · Cited by 1,253
Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span
Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., et al. (2009) · Science · doi:10.1126/science.1177221 · Cited by 1,120
Aguirre, V., Werner, E. D., Giraud, J., Lee, Y. H., Shoelson, S. E., & White, M. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m101521200 · Cited by 1,010
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Green, C. L., Lamming, D. W., & Fontana, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00411-4 · Cited by 714
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Blackwell, T. K., Steinbaugh, M. J., Hourihan, J. M., Ewald, C. Y., & Isik, M. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.008 · Cited by 622
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Vermeij, W. P., Dollé, M. E. T., Reiling, E., Jaarsma, D., Payan-Gomez, C., Bombardieri, C. R., Wu, H., Roks, A. J. M., Botter, S. M., van der Eerden, B. C., et al. (2016) · Nature · doi:10.1038/nature19329 · Cited by 315
Dehkhoda, F., Lee, C. M. M., Medina, J., & Brooks, A. J. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00035 · Cited by 304
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Silva-Vargas, V., Maldonado-Soto, A. R., Mizrak, D., Codega, P., & Doetsch, F. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.06.013 · Cited by 306
Reduced Expression of MYC Increases Longevity and Enhances Healthspan
Hofmann, J. W., Zhao, X., De Cecco, M., Peterson, A. L., Pagliaroli, L., Manivannan, J., Hubbard, G. B., Ikeno, Y., Zhang, Y., Feng, B., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.016 · Cited by 293
The Genetics of Aging: A Vertebrate Perspective
Singh, P. P., Demmitt, B. A., Nath, R. D., & Brunet, A. (2019) · Cell · doi:10.1016/j.cell.2019.02.038 · Cited by 259
Integrating the environmental and genetic architectures of aging and mortality
Argentieri, M. A., Amin, N., Nevado-Holgado, A. J., Sproviero, W., Collister, J. A., Keestra, S. M., Kuilman, M. M., Ginos, B. N. R., Ghanbari, M., Doherty, A., et al. (2025) · Nature Medicine · doi:10.1038/s41591-024-03483-9 · Cited by 211
Sex-Specific Gene Expression and Life Span Regulation
Tower, J. (2017) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2017.07.002 · Cited by 118
Regulation of longevity by FGF21: interaction between energy metabolism and stress responses
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.05.004 · Cited by 121
Energy Metabolism and Ageing in the Mouse: A Mini-Review
Azzu, V., & Valencak, T. G. (2017) · Gerontology · doi:10.1159/000454924 · Cited by 90
Danka Mohammed, C. P., Park, J. S., Nam, H. G., & Kim, K. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.01.007 · Cited by 69
Cytoplasmic mRNA turnover and ageing
Borbolis, F., & Syntichaki, P. (2015) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2015.09.006 · Cited by 39
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Metadata
- Authors
- Bartke, A., Sun, L. Y., & Longo, V.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2013-04
- Volume
- 93
- Issue
- 2
- Pages
- 571-598
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2125246804
- Cited by
- 287
- References
- 34
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- green
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