REGULATION OF REDOX PARAMETERS AND APOPTOSIS IN CALORICALLY RESTRICTED RODENTS
A. Aronis, O. Tirosh, R. Miskin
Institute of Biochemistry, Food Science and Nutrition, Hebrew University of Jerusalem, Rehovot 76100, Israel
Caloric restriction (CR) can extend the life span of multiple species
and is the only intervention known to attenuate aging in mammals.
Mechanisms mediating the CR influence are as yet unknown. There is
strong evidence that some of these mechanisms are associated with
mitochondrial functions. The purpose of our study was to search
parameters of apoptosis and redox in caloric restriction. We used two
models: 1) alpha-MUPA transgenic mice previously reported to
spontaneously eat less and live longer compared to their wild type (WT)
control. We used this model to search apoptotic aspects in young mice
(5-7 months old). To prove the similarity of this model to caloric
restriction we measured some parameters in calorically restricted WT
mice. 2) Old calorically restricted (CR) Sprague-Dawley rats compared
to ad libitum old and young rats. The CR rats were restricted at the
age of 10 months for 60% of their average food consumption (40% caloric
restriction); the restriction continued for 1 year. Here we report that compared to their ad-libitum fed
WT, young alpha-MUPA mice and short-term (8 weeks) caloric restricted
WT mice showed increased susceptibility to calcium-induced high
amplitude swelling of isolated liver mitochondria and increased
cytochrome c release, as well as enhanced caspase-3 activity of fresh
liver homogenates and increased DNA fragmentation in hepatocytes. In
addition, alpha-MUPA mice showed significantly decreased rate of
spontaneously occurring tumors at the old age, and significantly
reduced level of plasma IGF-1. Old calorically restricted rats showed a
lower level of lipid peroxidation and a higher rate of mitochondrial
reactive oxygen species (ROS) production compared to their ad libitum
control. Long-term caloric restriction in old rats approximated these
parameters to young rats. These results provide an indication that CR
can moderately enhance mitochondria-dependent apoptotic capacity and
improve redox parameters. Collectively, the results are consistent with the possibility that a
combination of long lasting, moderately extended apoptosis, decreased
oxidative damage (lipid peroxidation) and normalized ROS production
that is important for cell signaling could play a role in the
CR-induced anti-aging influence.
Key words:
Caloric restriction, aging, mitochondria, reactive oxygen species, apoptosis
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