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Table of Contents
Vol. 50, No. 5, 2004
Issue release date: September–October 2004
Section title: Experimental Section
Gerontology 2004;50:265–290
(DOI:10.1159/000079125)

Living and Dying for Sex

A Theory of Aging Based on the Modulation of Cell Cycle Signaling by Reproductive Hormones

Bowen R.L. · Atwood C.S.
aVoyager Pharmaceutical Corporation, Raleigh, N.C., bDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, and cSection of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin, Madison, Wisc., USA

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Article / Publication Details

First-Page Preview
Abstract of Experimental Section

Received: 12/12/2003
Accepted: 4/30/2004
Published online: 8/30/2004

Number of Print Pages: 26
Number of Figures: 3
Number of Tables: 3

ISSN: 0304-324X (Print)
eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER

Abstract

A mechanistic understanding of aging has yet to be described; this paper puts forth a new theory that has the potential to explain aging in all sexually reproductive life forms. The theory also puts forth a new definition of aging – any change in an organism over time. This definition includes not only the changes associated with the loss of function (i.e. senescence, the commonly accepted definition of aging), but also the changes associated with the gain of function (growth and development). Using this definition, the rate of aging would be synonymous with the rate of change. The rate of change/aging is most rapid during the fetal period when organisms develop from a single cell at conception to a multicellular organism at birth. Therefore, ‘fetal aging’ would be determined by factors regulating the rate of mitogenesis, differentiation, and cell death. We suggest that these factors also are responsible for regulating aging throughout life. Thus, whatever controls mitogenesis, differentiation and cell death must also control aging. Since life-extending modalities consistently affect reproduction, and reproductive hormones are known to regulate mitogenesis and differentiation, we propose that aging is primarily regulated by the hormones that control reproduction (hence, the Reproductive-Cell Cycle Theory of Aging). In mammals, reproduction is controlled by the hypothalamic-pituitary-gonadal (HPG) axis hormones. Longevity inducing interventions, including caloric restriction, decrease fertility by suppressing HPG axis hormones and HPG hormones are known to affect signaling through the well-documented longevity regulating GH/IGF-1/PI3K/Akt/Forkhead pathway. This is exemplified by genetic alterations in Caenorhabditis elegans where homologues of the HPG axis pathways, as well as the daf-2 and daf-9 pathways, all converge on daf-16, the homologue of human Forkhead that functions in the regulation of cell cycle events. In summary, we propose that the hormones that regulate reproduction act in an antagonistic pleiotrophic manner to control aging via cell cycle signaling; promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence.


Article / Publication Details

First-Page Preview
Abstract of Experimental Section

Received: 12/12/2003
Accepted: 4/30/2004
Published online: 8/30/2004

Number of Print Pages: 26
Number of Figures: 3
Number of Tables: 3

ISSN: 0304-324X (Print)
eISSN: 1423-0003 (Online)

For additional information: http://www.karger.com/GER


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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