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Brain growth receptors control lifespan.

Robinson R - PLoS Biol. (2008)

View Article: PubMed Central - PubMed

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Remarkably, inhibiting one or both of these two not only retards growth, but also extends lifespan, not just in lab animals, but possibly also in people: mutations that reduce the function of the IGF-1 receptor have recently been discovered in centenarians (who are also short)... Growth occurs throughout the body, and receptors for IGF-1 are found in every organ on virtually every cell... But Laurent Kappeler et al. now show that it is the IGF-1 receptors in the brain that set the pattern for growth and lifespan... The hypothalamus controls differentiation and daily function of the pituitary, sending it instructions in the form of “releasing hormones,” including growth hormone releasing hormone (GHRH)... To test this, they selectively knocked out IGF-1 receptors in the brains of mice, leaving peripheral receptors (including those in the pituitary) alone... Despite normal levels of IGF-1 receptors on the pituitary, the size of the gland was reduced, and its ability to produce GH was correspondingly smaller... Mean lifespan was also increased in the knockout mice, by about 10%... The effect on lifespan was curious, however... The increased mean lifespan can be explained by low peripheral GH and IGF-I, which is itself a consequence of reduced central IGF sensitivity, in keeping with previous studies that have shown that reduced peripheral IGF-I and GH extend lifespan... The reason for the second effect (unchanged maximum lifespan) is unclear and will require more investigation... These results suggest that IGF-1 feedback onto the hypothalamus during development plays a key role in determining the set-point of the somatotropic axis throughout life... While previous experiments have implicated IGF-1 suppression in lifespan extension, this study shows that central, rather than peripheral, suppression is sufficient to trigger the effect... Longer lifespan can also be the consequence of caloric restriction, and these results may indicate one mechanism that mediates that phenomenon.

No MeSH data available.


Somatoliberin produced by the developing hypothalamus (the red label represents hypothalamic somatoliberin, or GHRH) has an impact on late life mortality and lifespan in the mouse.
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pbio-0060274-g001: Somatoliberin produced by the developing hypothalamus (the red label represents hypothalamic somatoliberin, or GHRH) has an impact on late life mortality and lifespan in the mouse.


Brain growth receptors control lifespan.

Robinson R - PLoS Biol. (2008)

Somatoliberin produced by the developing hypothalamus (the red label represents hypothalamic somatoliberin, or GHRH) has an impact on late life mortality and lifespan in the mouse.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2573943&req=5

pbio-0060274-g001: Somatoliberin produced by the developing hypothalamus (the red label represents hypothalamic somatoliberin, or GHRH) has an impact on late life mortality and lifespan in the mouse.

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Remarkably, inhibiting one or both of these two not only retards growth, but also extends lifespan, not just in lab animals, but possibly also in people: mutations that reduce the function of the IGF-1 receptor have recently been discovered in centenarians (who are also short)... Growth occurs throughout the body, and receptors for IGF-1 are found in every organ on virtually every cell... But Laurent Kappeler et al. now show that it is the IGF-1 receptors in the brain that set the pattern for growth and lifespan... The hypothalamus controls differentiation and daily function of the pituitary, sending it instructions in the form of “releasing hormones,” including growth hormone releasing hormone (GHRH)... To test this, they selectively knocked out IGF-1 receptors in the brains of mice, leaving peripheral receptors (including those in the pituitary) alone... Despite normal levels of IGF-1 receptors on the pituitary, the size of the gland was reduced, and its ability to produce GH was correspondingly smaller... Mean lifespan was also increased in the knockout mice, by about 10%... The effect on lifespan was curious, however... The increased mean lifespan can be explained by low peripheral GH and IGF-I, which is itself a consequence of reduced central IGF sensitivity, in keeping with previous studies that have shown that reduced peripheral IGF-I and GH extend lifespan... The reason for the second effect (unchanged maximum lifespan) is unclear and will require more investigation... These results suggest that IGF-1 feedback onto the hypothalamus during development plays a key role in determining the set-point of the somatotropic axis throughout life... While previous experiments have implicated IGF-1 suppression in lifespan extension, this study shows that central, rather than peripheral, suppression is sufficient to trigger the effect... Longer lifespan can also be the consequence of caloric restriction, and these results may indicate one mechanism that mediates that phenomenon.

No MeSH data available.