Senescence: Dominant or Recessive in Somatic Cell Crosses?

125 Pages·1978·3.808 MB·English

by  F. Marott Sinex (auth.), Warren W. Nichols, Donald G. Murphy (eds.)

Senescence
Dominant or Recessive in
Somatic Cell Crosses?
CELLULAR SENESCENCE AND SOMATIC CELL GENETICS
Series editors: Warren W. Nichols Donald G. Murphy
Institute for Medical Research National Institute on Aging
Camden, New Jersey Bethesda, Maryland
Volume 1 REGULATION OF CELL PROLIFERATION AND DIFFERENTIATION
Edited by Warren W. Nichols and Donald G. Murphy
Volume 2 SENESCENCE: DOMINANT OR RECESSIVE IN SOMATIC CELL CROSSES?
Edited by Warren W. Nichols and Donald G. Murphy
Volume 3 MYCOPLASMA INFECTION OF CELL CULT URES
Edited by Gerard J. McGarrity, Donald G. Murphy, and Warren W. Nichols
Senescence
Dominant or Recessive in
Somatic Cell Crosses?
Edited by
Warren W Nichols
Institute for Medical Researcb
Camden, New Jersey
and
Donald G. Murphy
National Institute on Aging
Bethesda, Maryland
PLENUM PRESS . NEW YORK AND LONDON
Ubrary 01 Congl'8Ss Calaloging in Publieation Oata
Main entry under litle:
Senescence: dominant or reces,ive in $Omat;c cell croues7
(Cellular senescence and somatic cell genel;cs; 2)
"Proceedings 01 the Institute for Medical Research sympO$ium."
Includes inde:.:.
1. Cells-Aging-Congresses. 2. Cytogenetics-Congreues. 3. Somatic hybrids-Congnmes. I. Nichols,
Warren W. 11. Murphy, OonaldG. 111. In$litutefor Medieal RlKesn::h, Cemden. N. J. IV. Series. [ONLM:
1. Cytogenetics-Congre$$eS. 2. Cells, Cultured-Congreues. 3. Aging-Congrflss81i. Wl CEl295 v. 2
1976/WT1Q4 5475 1976J
QH608.S46 574.8'761 77-25004
ISDN 978-1-4684-2510-9 ISBN 978-1-4684-2508-6 (eBook)
DOIIO.1007/978-1-4684-2508-6
Proceedings 01 the Institute for Medical Research Symposium held in May 1976
e 1977 Plenum Press, New York
Softcover reprint ofthe hardcover Ist edition 19n
A Division 01 Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
All righn reserve<!
No part of this book may be reproduce<!, nore<! in aretrieval system, or transmitted,
in any form or by sny means, eleclronic, mechanical, photocepying, microfilming,
recording, or otherwise, without written permission !rom the Publisher
Organizing Panel
Donald G. Murphy, Health Scientist Administrator
National Institute on Aging, National Institutes
of Health, Bethesda, MD
Warren W. Nichols, Head, Dept. of Cytogenetics
Institute for Medical Research, Camden, NJ
v
Participants
Vincent J. Cristofalo. The Wistar Institute of Anatomy
and Biology, Philadelphia, PA
Carlo M. Croce, The Wistar Institute of Anatomy and Biology,
Philadelphia. PA
Richard L. Davidson, Harvard Medical School, Boston. NA
Robert DeMars, University of Wisconsin, Madison, WI
John W. Littlefield. Johns Hopkins University School of Medicine,
Baltimore. MD
Orlando J. Miller, College of Physicians & Surgeons.
Columbia University, New York, NY
Audrey L. Muggleton-Harris. University of Massachusetts Medical
School, Worcester, MA
Thomas H. Norwood. University of Washington. Seattle. WA
F. Marott Sinex. Boston University School of Medicine,
Boston. MA
Rosalind Yanishevsky, University of Colorado, Boulder. CO
vi
Preface
This monograph, Senescence; Dominant or Recessive In Somatic
Cell Crosses? represents the second annual workshop to promote
theory and concept development in aging research. These workshops
are part of a resource to bank cultured cells of special interest
to aging research that was established at the Institute for
Medical Research in Camden. New Jersey. by the National Institute
on Aging in 1974. The underlying theme of the workshops is the
use of cultured cells in a variety of somatic cell genetic
systems designed to define mechanisms of in vitra cellular scen
escence and the possible insights that this may provide to the
problems of in viva aging. The concept also includes bringing
together workers from a variety of disciplines to stimulate new
and innovative thoughts and work in the area. The current work
shop focuses on the relative role of nucleus and cytoplasm on
determining the in vitra lifespan of human diploid cells as well
as the relative influence of old and young cells when combined
within a single cell structure. The techniques and procedures
discussed should make significant contributions to understanding
in vitra senescence and may lead to the mapping of an area or
areas of the genome linked to senescence as is being accomplished
with viral transformation of normal cells.
Warren W. Nichols
Donald G. Murphy
~i
Contents
Theoretic Mechanisms of in vitpo Senescence
F. MaPott Sinex . . . . . . . . . . . . 1
Senescence in Ce1l Cu1ture: An Accumu1ation of Errors or
Terminal Differentiation?
Vincent J. GPistofaZo . . . . . . . . . . . . . . 13
Synkaryon and Heterokaryon Ana1yses of C1ona1 Senescence
Thomas H. Nopwood, HoZgep Hoehn~ AndPew O. Maptinez and
Geopge M. MaPtin. . . • . . . . . . . . . . . . . . 23
Comments about the paper by Norwood et a1., and an Idea
Re1ating Somatic Ce1l Mutations to Cel1u1ar Senescence
Robept DeMaps . . • . . . • . . . . . . . . . . . . 39
Fusion of Cytop1asts and Karyop1asts and How This Pertains
to Research of Aging and Transformation
AudPey L. MUggZeton-HaPPis. . . . . . . . . . . . . 57
Dominance or Recessiveness of the Senescent Phenotype in
Somatic Cel1 Fusions
RosaZind Yanishevsky and Gpetchen H. Stein. . . . . 73
Improved Techniques for the Fusion of Mamma1ian Ce11s
RichaPd L. Davidson . . . . . . . . . • . . 81
Mapping the SV40 Integration Sites in SV40-Transformed
Human Ce11s
CapZo M. Cpoce . . . . 87
Discussion of Dr. Croce's Paper
105
OPZando J. . . . . .
~ZZep
ix
x CONTENTS
Research on Ce11u1ar Senescence: Present and Future Directions
John W. LittZefieZd, Wai Nang Choy and
Joshua Epstein . . . . . . . . . . . . . . . . . . 111
Subject Index 121
THEORETICAL MECHANISMS OF IN VITRO SENESCENCE
F. Marott Sinex
Boston University School of Medicine
80 East Concord St., Boston, Mass. 02118
In this chapter we will discuss how somatic mutations might be
involved in the senescence of cells in culture and in the intact
organism. We will also discuss the possible role that stable pheno
typic variations may play in senescence.
Strictly speaking somatic mutations refer to changes in DNA
which alter the genetic information available to a cell and which
are capable of transmission to the cells progeny. In culture it
is sometimes difficult to tell whether DNA is truly altered or
whether a relatively stable change in regulation or differentiation
has occurred.
Without knowing what is altered it is difficult to really under
stand mechanisms, or to conceptualize means of intervention. If
aging is indeed due to mutation why does the mutation occur and how
can it be prevented? Is the mutation intrinsic to cell replication
or are base pairs actually altered chemically, even in the resting
state? On the other hand, might not stable phenotypic variants arise
through altered cellular regulation or differentiation in a cell
culture which would be propagated?
What can be demonstrated in tissue culture is the following:
Certain cell types, but thus far by no means all, can be propagated.
Different diploid cell types will undergo a variable number of
divisions characteristic of the tissue or origin. After a number of
population doublings the cells usually die or transform. Human
fibroblasts may be passaged a relatively large number of times before
dying out, and show little tendency to transform, differing from
rodent fibroblasts which transform much more readily. We can