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> Blennow Kaj 1958
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> Gu Harvest F >
Evidence that the g...
Evidence that the gene encoding insulin degrading enzyme influences human lifespan.
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- Hong, Mun-Gwan (author)
- Karolinska Institutet
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Reynolds, Chandra (author)
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Gatz, Margaret (author)
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- Johansson, Boo (author)
- Gothenburg University,Göteborgs universitet,Psykologiska institutionen,Department of Psychology
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Palmer, Jennifer C (author)
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- Gu, Harvest F (author)
- Karolinska Institutet
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Kehoe, Patrick G (author)
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- De Faire, Ulf (author)
- Karolinska Institutet
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- Pedersen, Nancy L (author)
- Karolinska Institutet
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- Prince, Jonathan A (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2008-04-30
- 2008
- English.
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In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 17:15, s. 2370-8
- Related links:
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https://academic.oup...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Studies in model organisms have demonstrated that components of insulin and insulin-like signaling pathways are involved in the regulation of lifespan but the relevance of those findings to humans has remained obscure. Here we provide evidence suggesting that variants of the gene encoding insulin-degrading enzyme (IDE) may be influencing human lifespan. We have employed a variety of models and diverse samples that reproducibly indicate the relative change in IDE genotype frequency across the age spectrum as well as allow the detection of association with age-at-death. A tenable molecular basis of this is suggested by the observation of genetic association with both fasting plasma insulin levels and IDE mRNA expression. Across populations the emergent genetic model is indicative of over-dominance, where heterozygotes of critical markers have increased IDE mRNA expression and insulin levels, and this is reflected in diminished heterozygosity at advanced age. A critical and replicating feature of this study is that change in IDE genotype frequency with advancing age appears to be occurring only in men, and this is supported in that insulin levels are only associated with IDE in men. Results suggest a relationship between a gene that is intimately involved in insulin metabolism and the determination of lifespan in humans, but over-dominance and gender specificity will be important parameters to consider clarifying the biological importance of these findings.
Keyword
- Aged
- Aged
- 80 and over
- Alternative Splicing
- Female
- Gene Expression
- Genotype
- Humans
- Insulin
- metabolism
- Insulysin
- genetics
- physiology
- Linkage Disequilibrium
- Longevity
- genetics
- Male
- Middle Aged
- RNA
- Messenger
- biosynthesis
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Hong, Mun-Gwan
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Reynolds, Chandr ...
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Gatz, Margaret
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Johansson, Boo
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Palmer, Jennifer ...
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Gu, Harvest F
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show more...
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Blennow, Kaj, 19 ...
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Kehoe, Patrick G
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De Faire, Ulf
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Pedersen, Nancy ...
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Prince, Jonathan ...
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show less...
- Articles in the publication
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Human molecular ...
- By the university
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University of Gothenburg
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Karolinska Institutet