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Review
. 2013 Jan;12(1):436-44.
doi: 10.1016/j.arr.2012.05.003. Epub 2012 Jun 15.

Organ-specific Mediation of Lifespan Extension: More Than a Gut Feeling?

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Free PMC article
Review

Organ-specific Mediation of Lifespan Extension: More Than a Gut Feeling?

Michael Rera et al. Ageing Res Rev. .
Free PMC article

Abstract

Multicellular organisms are composed of an interactive network of various tissues that are functionally organized as discrete organs. If aging were slowed in a specific tissue or organ how would that impact longevity at the organismal level? In recent years, molecular genetic approaches in invertebrate model systems have dramatically improved our understanding of the aging process and have provided insight into the preceding question. In this review, we discuss tissue and organ-specific interventions that prolong lifespan in the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. These interventions include reduced Insulin/IGF-1 signaling, knockdown of genes important for mitochondrial electron transport chain function and, finally, up-regulation of the Drosophila PGC-1 homolog. An emerging theme from these studies is that the intestine is an important target organ in mediating lifespan extension at the organismal level.

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Figure 1
Figure 1. Intestine-specific alterations in gene expression can extend lifespan in C. elegans and D. melanogaster
In the worm, the intestine is an important target organ for insulin/IGF-1 signaling (IIS)-mediated longevity. Overexpression of either DAF-16 or SKN-1 in the intestine leads to an increase in longevity. Furthermore, knock-down of cco-1, a mitochondrial complex IV subunit, using an intestine-specific promoter driving a cco-1 hairpin construct significantly increases worm lifespan. In the fly, a moderate reduction in IIS in intestinal stem (ISC) and progenitor (enteroblasts; EB) cells can extends lifespan. At the same time, up-regulation of dPGC-1, the Drosophila PGC-1 homolog, in ISCs/EBs also promotes longevity. Taken together, these findings point to the intestine as an important target organ for interventions that delay aging in invertebrate model systems. An emerging theme from these studies is that maintaining intestinal homeostasis may be important for the health and vitality of aging animals.

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