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senescence, and this situation is named as stress-induced premature senes-
cence (SIPS). Repeated nonlethal concentrations of H 2 O 2 or other oxidants
can be used to induce a senescent-like phenotype, including the loss of repro-
duction, the changes in morphology, the low response to growth factors, and
the reduced activity of cell cycle-related enzymes (80-85). Numerous cell
cultures were aged in vitro and employed as models of cellular aging in order
to test for basic biochemical and cellular processes of aging (86). Another
approach for studies on aging is the cultivation of cells obtained from young
and old humans or animals. However, due to the changes in the connective
tissue structure and cell binding to this with age, it is highly questionable
whether the isolated cells from young and old animals are representative (6).
In addition to that, since cultivated cells lack interaction with other tissues,
hormone stimulation, or regulation, and do not “age” in a normal environment,
all these models were seriously doubted, but nevertheless these models provide
a useful tool for some questions.
In an early study, Oliver et al. (87) demonstrated that in cultured fibroblasts
from normal donors, the levels of oxidatively modified proteins increase with
increasing PDbs. Several investigators reported that growth of cells on a col-
lagen matrix markedly enhanced the resistance of cells to stresses. Volloch and
Kaplan (72) have used collagen matrices on the aging process in human
primary fibroblasts IMR90 and they reported that, based on several aging-
related markers, growth of primary human cells on certain collagen matrices
results in at least temporary “rejuvenation” of aged cells and appears to sig-
nificantly reduce the rate of aging in young human cells.
The proliferation-related changes in protein oxidation and proteasome
activity during and after an acute oxidative stress have been studied. It was
demonstrated that the activity of the cytosolic proteasomal system declines
during proliferative senescence of human MRC-5 fibroblasts and was not able
to efficiently remove oxidized proteins in old cells. Whereas, in young cells,
removal of oxidized proteins was accompanied by an increase in the overall
protein turnover. This increase in protein turnover could not be seen in old
MRC-5 fibroblasts. This confirms the previous results that old fibroblasts are
much more vulnerable to the accumulation of oxidized proteins after oxidative
stress and are not able to remove these oxidized proteins as efficiently as
young fibroblasts (88). There was no significant difference in energy charge of
mitochondria if early and late passage cultures were compared, whereas the
NAD/NADH ratio was decreased in senescent cells (89).
Human BJ fibroblasts at confluency, at different PDb levels (including
those that are essentially postmitotic), were used under conditions where
cells do not divide. The same studies were also carried out in the proliferat-
ing cells. The activity of the cytosolic proteasome was found to have declined
dramatically during senescence of nondividing BJ fibroblasts. The peptidyl-
glutamyl-hydrolyzing activity was particularly affected. This decline in pro-
teasome activity was accompanied by a decrease in the overall turnover of
short-lived (radiolabeled) proteins in the nondividing BJ fibroblasts. However,
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