IGF-1 signaling and aging.
We briefly compare calorie restriction, GHRH-R and Pit-1 mutants with knockout phenotypes of GH receptor, IGF-1 receptor and p66Shc, to make some general conclusions. Growth, fertility and longevity phenotypes may dissociate in some of these mutants, and we try to interpret this. Follows a short discussion on the importance of genetic background for aging studies in mice. We then evoke studies in C. elegans showing that lifespan may be regulated in a non-cell-autonomous fashion, and that the nervous system could play a central role therein. Recent findings on DILP-2 regulation in Drosophila transpose this hypothesis of endocrine lifespan regulation to insects. Work in mice shows that inactivation of the insulin receptor specifically in the adipose tissue is sufficient to increase the mouse lifespan. In summary, exciting findings obtained in very different model organisms are rapidly converging and suggest that animal lifespan may be subject to endocrine regulation. Interestingly, the hypothalamus centralizes many age related hormonal regulations and at the same time participates in the integration of numerous nutritional signals, such that one could ask whether the hypothalamus may be at the crossroads of metabolic and endocrine lifespan regulation.
Holzenberger
Martin
M
Inserm U515, Hôpital Saint-Antoine, 75571 Paris 12, France. holzenberger@st-antoine.inserm.fr
Kappeler
Laurent
L
De Magalhaes Filho
Carlos
C
D000375:Aging / Q000502:physiology*; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005508:Food Deprivation; D013006:Growth Hormone / Q000378:metabolism; D007031:Hypothalamus / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008136:Longevity; D008297:Male; D051379:Mice; D023421:Models, Animal; D009154:Mutation; D010902:Pituitary Gland / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D013006:Growth Hormone; D007334:Insulin-Like Growth Factor I; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494185:Pou1f1 protein, mouse; C048250:somatotropin releasing hormone receptor