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Science Forum Index » Life Extension Forum » Genetic Suppression of GH-IGF-1 Activity, Combined...
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 Posted: Wed May 14, 2008 12:06 pm |
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Am J Nephrol. 2008 Apr 24;28(5):755-764 [Epub ahead of print] Links
Genetic Suppression of GH-IGF-1 Activity, Combined with Lifelong
Caloric Restriction, Prevents Age-Related Renal Damage and Prolongs
the Life Span in Rats.Zha Y, Taguchi T, Nazneen A, Shimokawa I, Higami
Y, Razzaque MS.
Department of Pathology, Nagasaki University Graduate School of
Biomedical Sciences, Nagasaki, Japan.
Aim: The aim of this study was to determine the effects of kidney
pathology on overall survival and longevity and the combined effects
of chronic suppression of growth hormone (GH)/insulin-like growth
factor-1 (IGF-1) activity and lifelong caloric restriction on age-
associated nephropathy. Methods: We analyzed the kidneys of rats with
suppressed GH activity through genetic manipulation with an antisense
GH transgene. Rats were fed normally or with a 30% calorie-restricted
diet for 24-26 months. The kidneys of male wild-type young (6 months)
and old (24-26 months) rats were compared with male hemizygote
transgenic young (6 months) and old (24-26 months) rats fed with
either regular diet or 30% calorie-restricted diet for their entire
life span. Results: The transgenic rats had relatively less pituitary
GH-secreting cells, and the plasma levels of IGF-1 were decreased by
53% in homozygote rats (tg/tg) and by 28% in hemizygote rats (tg/wt)
compared to wild-type rats (wt/wt) of the same age (6 months). Wild-
type rats fed the regular diet developed age-associated nephropathy as
they aged, showing severe inflammatory cell infiltration,
glomerulosclerosis, and tubulointerstitial fibrosis. In addition,
about 83% of the wild-type rats allowed to survive naturally showed
signs of nephropathy. In contrast, only 26% of the naturally surviving
hemizygote rats showed features of nephropathy, despite the fact that
these rats lived 8% longer (maximum survival 171 weeks) than the wild-
type rats (maximum survival 158 weeks). When chronic suppression of GH/
IGF-1 activity was combined with lifelong caloric restriction,
however, age- associated nephropathy was nonexistent in hemizygote
transgenic rats, and they showed about 30% increase in survival
(maximum survival 204 weeks). There was no significant difference in
the rate of neoplastic or nonneoplastic lesions (other than in the
kidney) in the regularly fed wild-type rats or in the calorie-
restricted hemizygote transgenic rats that survived longer.
Conclusion: We concluded that kidney pathology is an important
determinant of overall survival, and that prevention of kidney
pathology by dietary restriction, combined with chronic suppression of
GH/IGF-1 activity, significantly extends overall survival and
longevity. Copyright © 2008 S. Karger AG, Basel.
PMID: 18434714 [PubMed - as supplied by publisher] |
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