ISSN 10623604, Russian Journal of Developmental Biology, 2013, Vol. 44, No. 6, pp. 336–341. © Pleiades Publishing, Inc., 2013.
Original Russian Text © A.N. Khokhlov, 2013, published in Ontogenez, 2013, Vol. 44, No. 6, pp. 434–440.
The ability of tissues and organs to regenerate in the
overwhelming majority of multicellular organisms
declines with age (or, more precisely, in aging; see
The paper is based on the plenary lecture given by the author at the
international conference “Regenerative Medicine: Topical Issues”
(October 4–5, 2012, Kyiv, Ukraine).
below). As a rule, such a decline is determined by a
decrease in the ability of the corresponding body cells to
proliferate (Beausejour and Campisi, 2006; Macieira
Coelho, 2011), although cell proliferation is not the
only process that determines the efficiency of regenera
tion. Correspondingly, many gerontological concepts
Decline in Regeneration during Aging:
Appropriateness or Stochastics?
A. N. Khokhlov
Evolutionary Cytogerontology Sector, School of Biology, Moscow State University, Moscow, 119991 Russia
Received May 9, 2013; in final form, June 25, 2013
If you want to make God laugh,
tell Him your theory of aging.
—There is a standpoint according to which the suppression of the ability of cells in a multicellular
organism to proliferate, taking place during aging, as well as the corresponding decline in the regenerative
capacities of tissues and organs, is caused by the specialized mechanisms having emerged in the evolution that
decrease the risk of malignant transformation and, thereby, provide for protection against cancer. At the same
time, various macromolecular defects start to accumulate in senescent cells of the body, which, on the con
trary, elevate the probability for malignant transformation of these cells. Thus, according to the mentioned
concept, the restriction of cell proliferation is a doubleedged sword, which, on the one hand, decreases the
probability for malignant tumor development in young age and, on the other hand, limits the lifespan due to
accumulation of “spoiled” cells in old age. However, it remains unclear why normal human cells placed under
in vitro conditions and thus having no mentioned “anticancer” barriers, which function at the body level only,
NEVER undergo spontaneous malignant transformation. In addition, it is unclear how the freshwater hydra
escapes both aging and cancer, as it under certain conditions contains no postmitotic and senescent cells at
all and under these conditions (excluding the need for sexual reproduction) can live almost indefinitely, pos
sessing a tremendous regenerative potential (a new organism can emerge from even 1/100 part of the old one).
Presumably, the restriction of cell proliferation in an aging multicellular organism is not the result of a certain
special program. Apparently, there is no program of aging at all, the aging being a “byproduct” of the program
of development, whose implementation in higher organisms necessarily requires emergence of cell popula
tions with a very low and even zero proliferative activity, which actually determines the limited ability of the
corresponding organs and tissues to regenerate. On the other hand, the populations of highly differentiated
cells incapable or poorly capable of reproduction (e.g., neurons, cardiomyocytes, and hepatocytes) are the
particular factor that determines the normal functioning of higher animals and humans. Even regeneration
of such organs with the help of stem cells may interfere with the necessary links in elaborate systems. The
reductionism (“everything is determined by adverse changes in individual cells”), which has recently become
widespread in experimental gerontological research, has brought about several model systems for studying the
aging mechanisms in isolated cells (Hayflick phenomenon, stationary phase aging model, cellular kinetic
model for testing of geroprotectors and geropromoters, etc.). However, it currently seems that data obtained
using such models are inappropriate for an automatic extrapolation to the situation in the whole body. Pre
sumably, impairments in regulatory processes functioning at the neurohumoral level are the major players in
the mechanisms underlying aging of multicellular organisms rather than a mere accumulation of macromo
lecular damage in individual cells. It cannot be excluded that a disturbance of such regulation is the particular
reason for the abnormal INCREASE in proliferation intensity of some cell populations that are frequently
observed in old age and that lead to senile acromegaly and development of numerous benign tumors. It looks
like the quality of CONTROL over cells, organs, and tissues becomes poorer with age rather than the quality
of the cells themselves, which leads to an increase in the death rate.
: aging, regeneration, program, cell proliferation, cell aging, cancer