Exp Gerontol. 2004 Sep;39(9):1361-8. Links


Suppression of apoptosis by calorie restriction in aged kidney.

Lee JH, Jung KJ, Kim JW, Kim HJ, Yu BP, Chung HY.

Department of Pharmacy, Aging Tissue Bank, Pusan National University,
Gumjung-ku, Busan 609-735, South Korea.

Programmed cell death by apoptosis is regarded as an organism's protective
mechanism against the accumulation of defective cells. Apoptotic activity is
shown to be elevated in most aged tissues, and its intracellular regulation 
is
intricately manipulated by mitochondria. In this study, to determine the
progression of apoptosis during aging, we investigated the expression of
several key apoptosis-related markers in kidney of 12- and 24-month-old rats
.
Mitochondrial damage was detected by lipid peroxidation and Western blot
analysis in several target apoptotic proteins in aged rat kidney. Our result
s
showed that the expression levels of a pro-apoptotic Bax protein, was
significantly enhanced at the age of 24 months, while an anti-apoptotic
protein, Bcl-2, was reduced in the aged rat kidney. We also found that the
cytosolic cytochrome c level was significantly increased in the aged kidney.
However, these age-related changes were reversed by calorie restriction (CR)
,
exhibiting its modulatory action on apoptotic activity. Furthermore, caspase
-3
activation was markedly increased in kidney of 24-month-old rats fed ad libi
tum
(AL), as indicated by the cleaved, active form of caspase-3 (17-19kDa), whic
h
we found was replaced with the procaspase (32kDa) in the CR rats of both age
groups. We also found that a cleaved active form (85kDa) of poly (ADP-ribose
)
polymerase (116kDa inactivated form), which serves as a nuclear substrate fo
r
active caspase-3, was increased in aged AL kidney and was blunted by CR. In
addition, to investigate the oxidative status in aged kidney, we measured an
d
compared the malondialdehyde (MDA) and 4-hydroxynonenal (HNE) levels in aged
 AL
and CR rat kidneys. Our results showed increased MDA and HNE levels in aged 
AL
rats, while these levels were markedly lower in CR rats, even at 24 months.
These results indicate that the kidneys of rats fed ad libitum are under the
influence of high oxidative stress compared to CR rats. Thus, our present da
ta
strongly suggest that the apoptotic activity observed in the aged kidney is
likely modulated by the age-related oxidative status, and reversed by CR as 
a
result of its anti-oxidative and anti-aging actions.

PMID: 15489059 [PubMed - in process]

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