Genetic Signaling Pathway that Regulates Mammalian Life Span

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Hi,

there is a new study in Science (Issue, October 2, 2009) " Ribosomal Protein S6

Kinase 1 Signaling Regulates Mammalian Life Span " that shows when in mice a gene

that produces the Ribosomal S6 Kinease 1 (S6K1) protein is deleted the mice show

the same extended life span of 20% like mice on CR an similar gene expresssions

like CR. Only the female mice showed the extended life span. The life span of

the male mice was only short extended but they had health benefits. Inspection

of the T-cells also showed that they are more youthful. The block of this

pathway mimics the effect of calorie reduction.

Shortly was shown in Nature that Rapamycin also blocks the S6K1 pathway. There

is a growing evidence that there is a genetic signalling pathway that controls

the ageing process in mammals which is sensitive to drugs.

http://www.sciencemag.org/cgi/content/abstract/326/5949/140

Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span

Colin Selman,1,* M. A. Tullet,2 a Wieser,3 Elaine Irvine,1

J. Lingard,1 Agharul I. Choudhury,1 Marc

Claret,1 Hind Al-Qassab,1 le Carmignac,4 Faruk Ramadani,5 Woods,6

Iain C. A. ,4 Eugene Schuster,3

L. Batterham,1 Sara C. Kozma,7 ,7 Carling,6 Klaus

Okkenhaug,5 Janet M. Thornton,3 Partridge,2 Gems,2 Dominic J.

Withers1,8,9

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.

1 Institute of Healthy Ageing, Centre for Diabetes and Endocrinology, Department

of Medicine, University College London, London WC1E 6JJ, UK.

2 Institute of Healthy Ageing, Department of Genetics, Evolution and

Environment, University College London, London WC1E 6BT, UK.

3 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton,

Cambridge CB10 1SD, UK.

4 Division of Molecular Neuroendocrinology, Medical Research Council National

Institute for Medical Research, London NW7 1AA, UK.

5 Laboratory of Lymphocyte Signalling and Development, The Babraham Institute,

Cambridge CB22 3AT, UK.

6 Cellular Stress Group, Medical Research Council Clinical Sciences Centre,

Imperial College, London W12 0NN, UK.

7 Department of Cancer and Cell Biology, Genome Research Institute, University

of Cincinnati, Cincinnati, OH 45237, USA.

8 Metabolic Signaling Group, Medical Research Council Clinical Sciences Centre,

Imperial College, London W12 0NN, UK.

* Present address: Institute of Biological and Environmental Sciences,

University of Aberdeen, Aberdeen AB24 2TZ, UK.

9 To whom correspondence should be addressed. E-mail: d.withers@... or

d.withers@....