Bertrand H A, Masoro E J, Yu B P
Endocrinology. 1980 Aug;107(2):591-5. doi: 10.1210/endo-107-2-591.
Life-prolonging food restriction is known to delay physiological changes that occur during senescence. The aim of the present study was to learn if this nutritional manipulation also can influence changes that occur during the developmental phase of life. Male, specific pathogen-free Fischer 344 rats were fed ad libitum (group A) or 60% of the ad libitum intake (group R) beginning at 6 weeks of age. The group R rats had a markedly increased median length of life. Starting at 6 months of age, rats were periodically killed, and free adipocytes were prepared from epididymal and perirenal depots. The free adipocytes were used for the in vitro study of the promotion of lipolysis by glucagon. At 6 months of age and all older ages, adipocytes from group A rats were not responsive to the lipolytic action of glucagon; this agrees with earlier studies showing a marked loss in responsiveness to glucagon between 4-15 weeks of age. However, adipocytes from group R rats were quite responsive to glucagon at 6 and 12 months of age. Although after 12 months of age there was a loss in responsiveness to glucagon, this response remained significant through 36 months of age in the group R rats. Thus, life-prolonging food restriction delays not only functional changes that take place late in life (senescent changes) but also those occurring during the developmental period of life. The value of these findings as a model for experimental gerontology is discussed.
众所周知，延长寿命的食物限制可延缓衰老过程中发生的生理变化。本研究的目的是了解这种营养干预是否也能影响生命发育阶段发生的变化。从6周龄开始，对雄性无特定病原体的Fischer 344大鼠进行随意进食（A组）或按随意摄入量的60%进食（R组）。R组大鼠的中位寿命显著延长。从6月龄开始，定期处死大鼠，并从附睾和肾周脂肪库中制备游离脂肪细胞。游离脂肪细胞用于体外研究胰高血糖素对脂肪分解的促进作用。在6月龄及所有更大年龄时，A组大鼠的脂肪细胞对胰高血糖素的脂解作用无反应；这与早期研究结果一致，早期研究表明在4 - 15周龄之间对胰高血糖素的反应性显著丧失。然而，R组大鼠的脂肪细胞在6月龄和12月龄时对胰高血糖素相当敏感。虽然在12月龄后对胰高血糖素的反应性有所丧失，但在R组大鼠中，这种反应在36月龄时仍很显著。因此，延长寿命的食物限制不仅能延缓生命后期发生的功能变化（衰老变化），还能延缓生命发育阶段发生的变化。本文讨论了这些发现作为实验老年学模型的价值。
