Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity?
Present knowledge on the effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I) deficiency on aging and lifespan are controversial. Studying untreated patients with either isolated GH deficiency due to GH gene deletion, patients with multiple pituitary hormone deficiency due to PROP-1 gene mutation and patients with isolated IGF-I deficiency due to deletions or mutations of the GH receptor gene (Laron syndrome); it was found, that these patients despite signs of early aging (wrinkled skin, obesity, insulin resistance and osteopenia) have a long life span reaching ages of 80-90 years. Animal models of genetic GH deficiencies such as Snell mice (Pit-1 gene mutations) the Ames mice (PROP-1 gene mutation) and the Laron mice (GH receptor gene knock-out) have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting high amounts of GH have premature death. Those data raise the question whether pharmacological GH administration to adults is deleterious, in contrast to policies advocating such therapies.
Laron
Zvi
Z
Endocrinology and Diabetes Research Unit, Schneider Children's Medical Center, WHO Collaborating Center for the Study of Diabetes in Youth, Tel Aviv University, Tel Aviv, Israel. laronz@clalit.org.il
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D013006:Growth Hormone / Q000097:blood* / Q000172:deficiency* / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000378:metabolism; D046150:Laron Syndrome; D008136:Longevity; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D013997:Time Factors
D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone