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Science Forum Index » Life Extension Forum » Evidence that the Gene Encoding Insulin Degrading...
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 Posted: Fri May 09, 2008 1:55 pm |
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Hum Mol Genet. 2008 Apr 30 [Epub ahead of print] Links
Evidence that the Gene Encoding Insulin Degrading Enzyme Influences
Human Lifespan.Hong MG, Reynolds C, Gatz M, Johansson B, Palmer JC, Gu
HF, Blennow K, Kehoe PG, de Faire U, Pedersen NL, Prince JA.
Department of Medical Epidemiology and Biostatistics, Karolinska
Institutet, 171 77 Stockholm, Sweden.
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 only be occurring 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 towards clarifying the biological importance of
these findings.
PMID: 18448515 [PubMed - as supplied by publisher] |
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