Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span
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Mimicking Caloric Restriction: The extended life span and resistance to age-related diseases in animals exposed to caloric restriction has focused attention on the biochemical mechanisms that produce these effects. Selman et al. (p. 140 ; see the Perspective by Kaeberlein and Kapahi ) explored the role of the mammalian ribosomal protein S6 kinase 1 (S6K1), which regulates protein translation and cellular energy metabolism. Female knockout mice lacking expression of S6K1 showed characteristics of animals exposed to caloric restriction, including improved health and increased longevity. The beneficial effects included reduced fat mass in spite of increased food intake. Thus, inhibition of signaling pathways activated by S6K1 might prove beneficial in protecting against age-related disease.
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Reducing ribosome subunits or interfering with the TOR/ribosomal protein S6 kinase pathway changes lifespan in many species, including mammals.
“Depletion of ribosome subunits or interference with the target of rapamycin/ribosomal protein S6 kinase pathway, which functions to activate protein translation, were found to alter the lifespan of a variety of species including mammals (54–56).”
From Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability (2016) · cites this paper as [55]
Mice deficient in S6K1, a main mTORC1 substrate, are also long lived.
“and mice deficient in S6K1 (a main mTORC1 substrate) are also long lived.221”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [221]
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- Authors
- 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., Woods, A., Robinson, I. C. A., Schuster, E., Batterham, R. L., Kozma, S. C., Thomas, G., Carling, D., Okkenhaug, K., Thornton, J. M., Partridge, L., Gems, D., & Withers, D. J.
- Affiliations
- University College London (GB)
- European Bioinformatics Institute (GB)
- Institute of Healthy Ageing, Centre for Diabetes and Endocrinology, Department of Medicine, University College London, London WC1E 6JJ, UK.
- Medical Research Council (GB)
- Babraham Institute (GB)
- Imperial College London (GB)
- University of Cincinnati (US)
- Corresponding author
- Selman, Colin
- Withers, Dominic J.
- ORCID
- Venue
- Science
- Published
- 2009-10-02
- Volume
- 326
- Issue
- 5949
- Pages
- 140-144
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4954603
- OpenAlex
- W2014892893
- Cited by
- 1,120
- References
- 29
- Citations by year
- 2026: 26 · 2025: 28 · 2024: 38 · 2023: 64 · 2022: 50 · 2021: 59 · 2020: 57 · 2019: 58 · 2018: 73 · 2017: 65 · 2016: 57 · 2015: 82 · 2014: 84 · 2013: 90 · 2012: 107
- FWCI
- 29.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- BIROn (Birkbeck, University of London) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Kent Academic Repository (University of Kent) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust (066750)
- Biotechnology and Biological Sciences Research Council (BBS/E/B/0000C236, BBS/E/B/0000M979)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- ribosomal protein S6 kinase 1, mTOR signaling, caloric restriction, aging, lifespan, AMPK, age-related bone loss, immune dysfunction, motor impairment, insulin resistance
- MeSH terms
- Aging, Animals, Female, Gene Expression Regulation, Insulin, Liver, Longevity, Male, Mice, Inbred C57BL, Motor Activity, Protein Kinases, Transcription, Genetic, Signal Transduction, Bone Density, Gene Expression, T-Lymphocyte Subsets, Gene Deletion, Muscle, Skeletal, Caloric Restriction, Ribosomal Protein S6 Kinases, 90-kDa, Mice, Adipose Tissue, White, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases
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