Ribosomal protein S6 kinase 1 signaling regulates mammalian life span

Colin Selman; Jennifer M A Tullet; Daniela Wieser; Elaine Irvine; Steven J Lingard; Agharul I Choudhury; Marc Claret; Hind Al-Qassab; Danielle Carmignac; Faruk Ramadani; Angela Woods; Iain C A Robinson; Eugene Schuster; Rachel L Batterham; Sara C Kozma; George Thomas; David Carling; Klaus Okkenhaug; Janet M Thornton; Linda Partridge; David Gems; Dominic J Withers

doi:10.1126/science.1177221

Ribosomal protein S6 kinase 1 signaling regulates mammalian life span

Colin Selman, Jennifer M A Tullet, Daniela Wieser, Elaine Irvine, Steven J Lingard, Agharul I Choudhury, Marc Claret, Hind Al-Qassab, Danielle Carmignac, Faruk Ramadani, Angela Woods, Iain C A Robinson, Eugene Schuster, Rachel L Batterham, Sara C Kozma, George Thomas, David Carling, Klaus Okkenhaug, Janet M Thornton, Linda PartridgeDavid Gems, Dominic J Withers

Aberdeen Centre For Environmental Sustainability

Research output: Contribution to journal › Article › peer-review

901 Citations (Scopus)

Abstract

Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.

Original language	English
Pages (from-to)	140-144
Number of pages	5
Journal	Science
Volume	326
Issue number	5949
DOIs	https://doi.org/10.1126/science.1177221
Publication status	Published - 2 Oct 2009

Keywords

AMP-activated protein kinases
adipose tissue, white
aging
animals
bone density
caloric restriction
female
gene deletion
gene expression
gene expression regulation
insulin
liver
longevity
male
mice
mice, inbred C57BL
motor activity
muscle, skeletal
protein kinases
ribosomal protein S6 kinases, 90-kDa
signal transduction
T-lymphocyte subsets
transcription, genetic

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10.1126/science.1177221

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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., ... Withers, D. J. (2009). Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science, 326(5949), 140-144. https://doi.org/10.1126/science.1177221

Selman, C, Tullet, JMA, Wieser, D, Irvine, E, Lingard, SJ, Choudhury, AI, Claret, M, Al-Qassab, H, Carmignac, D, Ramadani, F, Woods, A, Robinson, ICA, Schuster, E, Batterham, RL, Kozma, SC, Thomas, G, Carling, D, Okkenhaug, K, Thornton, JM, Partridge, L, Gems, D & Withers, DJ 2009, 'Ribosomal protein S6 kinase 1 signaling regulates mammalian life span', Science, vol. 326, no. 5949, pp. 140-144. https://doi.org/10.1126/science.1177221

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title = "Ribosomal protein S6 kinase 1 signaling regulates mammalian life span",

abstract = "Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.",

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author = "Colin Selman and Tullet, {Jennifer M A} and Daniela Wieser and Elaine Irvine and Lingard, {Steven J} and Choudhury, {Agharul I} and Marc Claret and Hind Al-Qassab and Danielle Carmignac and Faruk Ramadani and Angela Woods and Robinson, {Iain C A} and Eugene Schuster and Batterham, {Rachel L} and Kozma, {Sara C} and George Thomas and David Carling and Klaus Okkenhaug and Thornton, {Janet M} and Linda Partridge and David Gems and Withers, {Dominic J}",

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AU - Selman, Colin

AU - Tullet, Jennifer M A

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AU - Irvine, Elaine

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AU - Choudhury, Agharul I

AU - Claret, Marc

AU - Al-Qassab, Hind

AU - Carmignac, Danielle

AU - Ramadani, Faruk

AU - Woods, Angela

AU - Robinson, Iain C A

AU - Schuster, Eugene

AU - Batterham, Rachel L

AU - Kozma, Sara C

AU - Thomas, George

AU - Carling, David

AU - Okkenhaug, Klaus

AU - Thornton, Janet M

AU - Partridge, Linda

AU - Gems, David

AU - Withers, Dominic J

PY - 2009/10/2

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N2 - Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.

AB - Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.

KW - AMP-activated protein kinases

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KW - aging

KW - animals

KW - bone density

KW - caloric restriction

KW - female

KW - gene deletion

KW - gene expression

KW - gene expression regulation

KW - insulin

KW - liver

KW - longevity

KW - male

KW - mice

KW - mice, inbred C57BL

KW - motor activity

KW - muscle, skeletal

KW - protein kinases

KW - ribosomal protein S6 kinases, 90-kDa

KW - signal transduction

KW - T-lymphocyte subsets

KW - transcription, genetic

U2 - 10.1126/science.1177221

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SP - 140

EP - 144

JO - Science

JF - Science

SN - 0036-8075

IS - 5949

ER -

Ribosomal protein S6 kinase 1 signaling regulates mammalian life span

Abstract

Keywords

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