Vascular aging countered by CR

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Hi All,

The fairly vague Medline citation and abstract of:

Kim JW, Zou Y, Yoon S, Lee JH, Kim YK, Yu BP, Chung HY.

Vascular aging: molecular modulation of the prostanoid cascade by calorie

restriction.

J Gerontol A Biol Sci Med Sci. 2004 Sep;59(9):B876-85.

PMID: 15472149

was presented in:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=15472149 & query_hl=28

More detail may be enlightening.

The investigators appeared to not use the now standard procedure in the upscale

CR

labs of adding extra vitamins and minerals with or without extra protein to the

media of the CRed rats.

Abbreviations include prostaglandin E2 (PGE2), PGI2, thromboxane A2 (TXA2),

cyclooxygenases (COXs) and glutathione peroxidase (GSH-Px).

See the below from the full-text, for which the pdf is available.

.... Fischer 344 rats were fed a diet of the following

composition: 21% soybean protein, 15% sucrose, 43.65%

dextrin, 10% corn oil, 0.15% a-methionine, 0.2% choline

chloride, 5% salt mix, 2% vitamin mix, and 3% Solka-Floc

(cellulose). The semisynthetic diet was supplied by Purina

Test Chow Co. (St. Louis, MO). ... All rats were fed

ad libitum (AL) until 6 weeks of age, and then divided into

AL and CR groups. Animals in the CR group were fed

a whole food intake that was restricted by 40% of that for the

AL group. Histopathological examination revealed no

evidence of nephritic lesions in these soy protein-fed Fischer

rats even at the advanced age of 24 months (18).

.... RESULTS

Effects of Age and CR on Prostanoids

Serum prostanoid contents were analyzed and compared

for AL and CR rats at 6 and 24 months of age. The PGE2

content was strongly affected by age as shown in Figure 1.

The serum content level of PGE2 for animals in the 24-

month-old AL group was 2.2-fold higher than for animals in

the 6-month-old group. Our results show that CR signifi-cantly

attenuated this age-related increase in PGE2 (Figure

1). TXA2 content also increased with age. Serum from rats

in the 24-month-old AL group showed an approximately

40% greater TXA2 content compared with rats in the 6-

month-old group. In the case of PGI2, although analysis of

serum PGI2 levels showed a substantial increase during

aging, CR did not suppress this increase.

[Of the 6, 12, 18 and 24 month times, all except the 6-months PGE2 levels were

noticeably less with CR.]

We also measured PGI2 and TXA2 levels in arachidonic

acid-treated aorta homogenates. As shown in Figure 2, the

age-related increase of PGI2 was estimated to be approxi-mately

40% in the AL-fed animals, but was shown to be

effectively attenuated in CR animals. When comparing

young and old animals in the AL group, we found the level

of TXA2 was enhanced about approximately 1.5-fold by the

aging process. We also found that CR animals showed

lower age-related increases in TXA2 levels than their AL-fed

counterparts (Figure 2).

[All values were noticeably lower with CR.]

Effects of Age and CR on the Prostaglandin Cascade System

Production of prostanoids is catalyzed by an enzyme

cascade that includes PLA2 s, COXs, and terminal PG

synthases. We evaluated the expression of prostanoids

cascade enzymes by RT-PCR. Between two isoforms of

PLA2 , we found the mRNA levels of cPLA2 increased

significantly during aging, while sPLA2 levels showed no

change (Figure 3).

[PGES levels were just over half the levels for CR versus AL at 6 months.]

COX also exists in two isoforms. COX-1 is expressed

constitutively while COX-2 is induced in many cell types by

the stimulation of inflammatory cytokines. COX-2 has been

identified as a key enzyme in the regulation of PG synthesis

and an important player in the inflammation process. We

observed considerable amounts of COX-2 mRNA in the

aorta of old rats, in contrast to the negligible amounts found

in young rats. On the other hand, approximately equal

amounts of COX-1 were found in young and old rats (Figure

3). Accordingly, in situ detection of COX-1 and COX-2

protein levels by immunohistochemical staining showed the

same tendencies (Figure 4).

Among the terminal PG synthases, we examined PGI2

synthase (PGIS) and PGE2 synthase (PGES) expression in

the aorta of young and old rats fed AL and CR diets.

Although no significant differences in PGES expression

were shown between young and old rats, the PGIS mRNA

level was significantly higher in old rats than in young rats

(Figure 4). Taken together, these data suggested that up-regulated

cPLA2 , COX-2, and PGIS were likely responsible

for increased PG production during aging.

The beneficial effects of CR on these enzymes were also

detected. CR significantly suppressed age-associated in-creases

in cPLA2 and COX-2.

Effects of Age and CR on Antioxidative Enzymes

SOD, catalase, and GSH-Px are three major antioxidant

enzymes that play a central role in an organism’s ability to

protect against oxidative stress during ROS metabolism.

The protein levels of these antioxidant enzymes during

aging were determined by Western blot analysis. As shown

in Figure 5, SOD and catalase levels were unchanged during

the aging process, while GSH-Px levels were very high in

old AL rats. CR rats were shown to have up-regulated

catalase protein levels, but showed no change in SOD

levels. On the other hand, we observed that CR blunted the

age-related induction of GSH-Px.

We also compared differences in antioxidant capacity

between young and old aorta of CR and AL-fed rats. Data in

Figure 5C indicate that, in the AL group, the aorta from old

rats had a significantly weakened antioxidant capacity for

H2O2 and the hydroxyl radical scavenging activity than that

from young AL rats, while the impaired antioxidant capacity

in old rats was attenuated by CR treatment.

....

Al Pater, PhD; email: old542000@...

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