Food restriction, hormones, genes and aging

Abstract

Pituitary hormones play an important role in aging and longevity. Hypophysectomy retards aging but shortens life in the rat. However, life-long studies show that when young male Wistar rats aged 60 days are hypophysectomized (HYP) and receive 1 mg cortisone once per week and the same amount of food as food restricted (FR) rats they age more slowly than control (C) or FR rats. HYP rats have the slowest aging in collagen fibre strength, kidney basement membrane thickness, thoracic aorta width, percentage of gross tumors at death and live significantly longer suggesting that ACTH and glucocorticoids may have anti-aging actions. Other pituitary hormones also play key roles in aging. Many studies have focused on growth hormone, IGF-1 and insulin. Deficiencies or perturbations in the expression of other pituitary factors have uncovered roles for thyroid stimulating hormone and luteinizing hormone as well. Study of the interaction of mouse longevity genes with FR have revealed differential responses in endocrine mutants. In Ames dwarfs, FR produced further increases in insulin sensitivity and longevity. In contrast, identical regimen of FR in GHRKO mice did not further augment their insulin sensitivity, did not affect longevity of males and produced a minor increase in maximal longevity of females. These results support the importance of altered insulin signaling in mediating the effects of GH on longevity. Overall, it is clear that pituitary hormones affect age-related physiological processes and longevity. FR alters expression of these hormones thus contributing to delayed aging and lifespan extension observed in FR rodents.