Modulatory Effect of Dietary Restriction on the Advance of Senescence in Senescence Accelerated Mouse (SAM)

饮食限制对衰老加速小鼠（SAM）衰老进展的调节作用

基本信息

批准号：
01480165
负责人：
TAKEDA Toshio
金额：
$ 4.48万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480165/
关键词：
Senescence Accelerated Mouse calorie restriction immune responsiveness modulation of aging auto-antibody

项目摘要

1. The effects of age and dietary restriction on immune response were investigated using an animal model of accelerated senescence, SAM. Spleen weight and total number of splenic cells were significantly lower in the food-restricted group (fed 60% of energy intake of ad libitum fed) at 8 mo of age. Percentages of T and B cells in the splenic cells were not significantly different between the two groups. The number of direct hemolytic plaqueforming cells per 10^6 spleen cells 4 d following immunization with SRBC and DNP-Ficoll was significantly greater in the 8-mo-old mice in the food-restricted group than in the control (ad libitum fed) group. Mitogen responses to concanavalin A and LPS were maintained in the food-restricted group but were depressed in the control group at 8 mo. In addition, though autoantibody to single-stranded DNA increased in the control group with advancing age, there was a steady decrease in the food-restricted group until 8 mo. Therefore, our results suggest that when SAM are subjected to food restriction, there may be a modulatory effect on te immune dysfunction associated with advancing age.2. After crossing with high responders, Blo. BR mice, about 12% of (Blo.BR SAM-P/1) (BRP) F_2 mice showed low responsiveness, as did SAM-P/1 mice, against two T-dependent antigens, SRBC and HRBC. Based on the incidence of the low responders in F_2 generation and statistical analyses, tehyporesponsiveness was postulated to be controlled by two genes. To survey the location of these genes, linkage analyses were performed in the F_2 mice using a large set of genetic markers. These results suggest that one of genes controlling the hyporesponsiveness of SAM-P/1 mice is linked t both Gpi-1 and c loci and that it locates at a more proximal site on Chr. /.

1. 使用加速衰老动物模型 SAM 研究了年龄和饮食限制对免疫反应的影响。 8月龄时，食物限制组（自由采食能量摄入的60%）的脾脏重量和脾细胞总数显着较低。两组之间脾细胞中 T 细胞和 B 细胞的百分比没有显着差异。在用 SRBC 和 DNP-Ficoll 免疫后 4 天，限制食物组的 8 个月大小鼠中每 10^6 个脾细胞的直接溶血空斑形成细胞数显着高于对照组（随意喂养）组。 8 个月时，食物限制组中伴刀豆球蛋白 A 和 LPS 的有丝分裂原反应得以维持，但对照组中则降低。此外，虽然对照组的单链 DNA 自身抗体随着年龄的增长而增加，但食物限制组的抗体在 8 个月之前一直稳定下降。因此，我们的结果表明，当 SAM 受到食物限制时，可能会对与年龄增长相关的免疫功能障碍产生调节作用。2．与高反应者交叉后，Blo。 BR 小鼠中，约 12% 的 (Blo.BR SAM-P/1) (BRP) F_2 小鼠与 SAM-P/1 小鼠一样，对两种 T 依赖性抗原 SRBC 和 HRBC 显示出低反应性。根据F_2代低反应者的发生率和统计分析，推测低反应性是由两个基因控制的。为了调查这些基因的位置，使用大量遗传标记在 F_2 小鼠中进行连锁分析。这些结果表明，控制 SAM-P/1 小鼠反应性低下的基因之一与 Gpi-1 和 c 位点均相关，并且位于 Chr 上更近的位点。 /。