1022-7954/01/3711- $25.00 © 2001
Russian Journal of Genetics, Vol. 37, No. 11, 2001, pp. 1213–1223. Translated from Genetika, Vol. 37, No. 11, 2001, pp. 1445–1458.
Original Russian Text Copyright © 2001 by Akifyev, Potapenko.
In the beginning of the 21st century it became evi-
dent that biology of aging lags behind genetics. During
a hundred years, genetics has advanced from a hypoth-
esis on hereditary factors (genes) to their chemical
identiﬁcation and isolation in virtually any quantities
required, directed in vitro modiﬁcation and introduc-
tion in recipient cells often obtaining desired results.
These advances in genetics are based on clear under-
standing of the chemical substrate of heredity and
By contrast, although biology of aging has been
recently focused on studying the nature of the initial
substrate of aging (ISA) , hundreds of hypotheses to
this effect have been put forward in the past 20–25
years . This shows that this discipline is at the ﬁrst
stage of formation. Recall that as early as in the ﬁrst
decades of its existence, genetics was transformed from
the formal Mendelian doctrine into the chromosomal
theory of heredity that related hypothetical hereditary
factors to chromosomes, which are visible under light
microscopy . In other words, genes were regarded as
parts of speciﬁc material structures. This route is still
ahead of biology of aging. However, this discipline
must pass it. Otherwise, it will not integrate into molec-
ular biology remaining at the backyard of science and
failing hopes of the aging humankind .
Thus, only discovering the ISA (if it exists) can
transform biology of aging into a modern scientiﬁc dis-
cipline like genetics was transformed by the demonstra-
tion that DNA is the basis of heredity.
In the present paper, we consider our concept of the
animal ISA based on the literature evidence and the
results of more than two decades of our experimental
studies of senescence mechanisms. Apparently, the
substrate of aging is nuclear DNA. We believe that this
ﬁnding may open a new ﬁeld of mutual interests of
genetics and biology of aging.
DEATH AS THE RESULT OF AGING:
POSSIBLE OR INEVITABLE?
First, we consider some general approaches to ani-
mal senescence and its biological role, which should be
reﬁned or even revised. This primarily concerns the
process of aging proper.
The most common view on aging deﬁnes it as regu-
lar destructive process of age-related changes of the
body that reduces its adaptive capabilities and increases
the probability of death . This deﬁnition currently
accepted by almost all gerontologists was coined by
Comfort more than 30 years ago and reiterated in his
subsequent fundamental works . It was inferred from
studying age-related alterations of animal cells and
bodies. Examination of these alterations provides myr-
iad possibilities since almost all tissues and organs
undergo certain, albeit sometimes not synchronous ,
changes during aging . This fact explains the exist-
ence of as many as 400 hypotheses on mechanisms of
aging . For instance, one of these hypotheses
ascribes mammal senescence to changes in collagen
. Hence, it cannot be a priori stated that collagen
does not play the role of the ISA. Other hypotheses pos-
tulate that aging is initiated by changes in mitochon-
dria, membranes, vascular walls, endocrine glands, etc.
. Most of these hypotheses refute the existence of a
speciﬁc aging mechanism and source.
Aging begins with the termination of the compensa-
tory ability of the body, i.e., its capability to cope with
destructive environmental effects . However, as there
is a multitude of age-related changes, which can occur
simultaneously in one organ and even in one cell, the
ISA concept may be no more than a working hypothesis
Nuclear Genetic Material as an Initial Substrate
of Aging in Animals
A. P. Akifyev
and A. I. Potapenko
Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, 117977 Russia
Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 119991 Russia
Received May 25, 2000; in ﬁnal form, March 23, 2001
—General properties of aging in animals are considered on the basis of the literature evidence and the
results obtained by the authors of this paper. The existence of a speciﬁc aging mechanism is inferred. The oper-
ation of this mechanism is controlled not only by genes but also by particular noncoding genomic sequences
with variable structure. The beginning of senescence in animals is determined by DNA lesions located in neural
cells and probably in a minor genomic fraction. The authors refute the narrow concept of aging as a mechanism
increasing the probability of death. Mortality as a continuous process occurring with the probability of 100 per-
cent is an integral attribute of living organisms on the Earth.