Lifespan is controlled by levels of the hormone IGF-1 synthesized during early life

October 28 2008

The hormone IGF-1 (Insulin-like growth factor) which is synthesized during early life to stimulate growth and development also controls lifespan. It achieves this by interacting with other growth factors and in particular growth hormone (GH), that it regulates according to environmental factors. To reach these conclusions, the Inserm unit 893 team of Martin Holzenberger “Centre de recherche Saint-Antoine”, reduced the number of IGF-1 receptors present in a mouse brain by mutagenesis. When IGF-1 levels became low, growth was slowed and the lifespan of these mice was prolonged. These results are published in the journal PLoS Biology.

Previous publications have shown that the growth factor IGF, a hormone synthesized from the beginning of life in worms and insects, has a crucial importance for growth, development and metabolism. However these studies also showed that a low production of IGF prolonged the lifespan of these species. Martin Holzenberger and his team wanted to know if the same was true in mammals. They therefore carried out mutagenesis in mice in order to reduce the levels of brain IGF receptors to half their normal values. The mice obtained were in good health despite a few metabolic abnormalities and delayed growth. At adult age, their organs (heart, lung, liver, kidneys etc.) were smaller than the normal and their blood glucose and HDL cholesterol levels were increased. These changes in no way disturbed the fate of these rodents which had a longer life expectancy than normal mice! Their mortality rates at one hundred weeks, equivalent to 70 years in man, were six times lower. Their slower growth seemed to allow them to capitalize on their lifespan.

Continuing their investigations, these researchers found that by reducing the sensitivity of the brain to IGF-1, they caused a cascade of events in which several other growth factors were involved and in particular growth hormone (GH). IGF-1 does not therefore act alone. It controls a whole network of hormones, the combined action of which enables the organism to adjust its growth according to various environmental stimuli. For example, food restriction at the start of life causes, among other things, a fall in IGF-1 levels in order to slow down growth.

“These studies show that each individual acquires a height and metabolism partly defined in early childhood according to the environment in which he/she lives. Overfeeding children in order to make them grow taller and put on weight may shorten their life expectancy,” explains Martin Holzenberger. “Moreover, growth hormone is sometimes used off-label. This is the case for example in certain elderly persons who want to delay the effects of aging or sportsmen who seek to gain in size and performance. These persons may actually be destroying their life capital while seeking to increase their strength,” concluded the researcher.

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“Brain IGF-1 Receptors Control Mammalian Growth and Lifespan through a Neuroendocrine Mechanism”

Laurent Kappeler1, Carlos De Magalhaes Filho1,2, Joëlle Dupont3, Patricia Leneuve1,Pascale Cervera4, Laurence Périn1, Catherine Loudes5, Annick Blaise1,2, Rüdiger Klein6, Jacques Epelbaum5, Yves Le Bouc1,2 and Martin Holzenberger1

(1) Inserm Unit 893, Hôpital Saint-Antoine, 75012 Paris, France
(2) Université Pierre-et-Marie-Curie, 75005 Paris, France
(3) INRA, 37380 Nouzilly, France
(4) Service d’Anatomopathologie, Hôpital Saint-Antoine, 75012 Paris, France
(5) Inserm Unit 549, Centre Paul Broca, 75014 Paris, France
(6) Department of Molecular Neurobiology, Max-Planck Institute of Neurobiology, 82152 Munich-Martinsried, Germany

PLoS Biology, vol.6 (issue10): e254. doi:10.1371/journal.pbio.0060254 October 28, 2008

Researcher contact

Martin Holzenberger
Inserm Research Director
Inserm UMR893, Saint-Antoine Hospital
Phone: +33 (0)1 49 28 46 34

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