February 2, 1968

Dr. Gabe J. Maletta
Adult Development and Aging Branch
National Institute of Child Health

and Human Development
Department of Health Education and Welfare
National Institutes of Health
Bethesda, Maryland 20014

Dear Dr. Maletta:
Thank you for your letter of January 29.

I really was not acting as pecponent of any particular theory
of cellular aging in my remark relating this to studies on DNA.
In fact at the moment I am rather skeptical about any unitary
theory to account for aging in every aspect. I have no doubt
that genetic and chromosomal lesions play some part in some
circumstances but feel that it fs much too soon to exclude the
simultaneous action of many other mechanisms.

VLLaATyl

The point that underlies my remark is that whatever the funda-
mental mechanisms a knowledge of DNA replication and its controls
will surely be highly instrumental both in diagnosing the funda-
mental difficulties and in proposing ways of meeting them.
Whatever else it is aging is certainly a developmental phenomenon
and an indispensable part of our understanding of it will concern
the factors that control the integrity, replication and expression
of the genetic mechanism. We certainly do need to find out all
we can about the status of the DNA and of the DNA-replicating
enzymes in aging tissues; this is by no means in contradiction

to theories that would put a larger emphasis on chemical modifi-
cations of connective tissue proteins or on disorganization at
much higher levels - cells and tissues - than on the DNA.

These remarks should however not be taken as any lack of interest
in meeting you and please do let me know when you may happen to
be in this vicinity.

Sincerely,

Joshua Lederberg,
Professor of Genetics

JL/ gem