1062-3604/01/3204- $25.00 © 2001
Russian Journal of Developmental Biology, Vol. 32, No. 4, 2001, pp. 199–204. Translated from Ontogenez, Vol. 32, No. 4, 2001, pp. 245–251.
Original Russian Text Copyright © 2001 by Zainullin, Moskalev.
It was already proposed in 1982 that senescence
may be due to the pleiotropic effect of a group of genes
carrying the information about programmed cell death
(apoptosis). On the one hand, this program is essential
for the development and functioning of the multicellu-
lar organism; on the other hand, it makes the death of
cells inevitable in the adult organism. In this case,
senescence may be a consequence of the gradual loss of
functionally active cells (Umansky, 1982).
Apoptosis may be involved in senescence in two
ways (Warner, 1997; Warner
(1) Damaged senescing cells, such as ﬁbroblasts and
hepatocytes, are removed through apoptosis, and they
can be later be replaced by means of cell proliferation,
so that the tissue homeostasis is preserved.
(2) Postmitotic cells, such as neurons and cardiomy-
ocytes, are eliminated through apoptosis, and they can-
not be replaced, which leads to pathologies.
Active studies of the pattern of apoptosis during
senescence revealed many examples of age-related
deregulation of this processes and some mechanisms
underlying these changes. Their relationship with vari-
ous age-related pathologies has also been shown. It
turned out that senescence of many cell types is associ-
ated with the changes in their sensitivity to apoptosis.
Most cell types are characterized by an age-related
increase in sensitivity to the induction of apoptosis:
hepatocytes, T-cells, oocytes, megakaryocytes, mac-
rophages, chondrocytes-endotheliocytes, neurons,
splenocytes, and cardiomyocytes. However, this sensi-
tivity remains unchanged for the keratinocytes and
even decreases for the ﬁbroblasts (Zainullin
A number of genes involved in the control of apop-
tosis in both animals and plants undergo age-related
changes in their expression (the table).
Apoptosis is as evolutionarily conservative and
inherent in each of the cells as senescence itself.
In animals, apoptosis plays an important role in tis-
sue homeostasis (maintenance of a constant number of
cells). It realizes the protective elimination of old, pre-
neoplastic, or excessive cells. Hence, the disfunction-
ing of the program of cell death may directly affect the
development of the degeneration of neoplastic age-
related changes (James
Role of Apoptosis in Age-Related Pathologies
V. G. Zainullin
and A. A. Moskalev
Institute of Biology, Komi Research Center, Ural Division, Russian Academy of Sciences,
Syktyvkar, 167000 Komi Republic, Russia
Syktyvkar State University, Syktyvkar, 167982 Russia
Received July 5, 1999; in ﬁnal form, March 6, 2000
—A review of recent data concerning the apoptotic death of cells during senescence at the organismic
level. The data analyzed suggest interrelations between apoptosis deregulation and some age-related patholo-
gies and senescent phenotypes. Genetic aspects and possible mechanisms of age-related changes in the program
of apoptosis are considered. It has been proposed that age-related deregulation of apoptosis is a mechanism of
: senescence, apoptosis, life span, age-related pathologies
Age-related expression of apoptosis inducers and inhibitors
Inducers of apoptosis Inhibitors of apoptosis
Increases p53, TNF-
, DNAse I,
, active oxygen forms,
-amyloid peptide, ceramide,
in fibroblasts (mammals)