Saturday, 25 August 2012

Potentially conserved pro-ageing pathways, their interconnections and possible targets for intervention

PubMed Central, Figure 1: Nature. 2008 August 28; 454(7208): 1065–1071. doi: 10.1038/nature07216 from

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In this very simplified depiction, three main pathways, the IIS (insulin/insulin-like growth factor 1 (IGF-I) signalling) pathway, TOR and mitochondrial pathway, are indicated.

The pro-ageing activities of these pathways are conserved across species, with energy sensors, such as AMPK, as potentially important hubs in the complex networks that integrate them.

However, it is important to note potential dissimilarities among species as well. Most, if not all, defects in the mitochondrial respiratory chain are lethal or cause disease in humans, but can increase lifespan in nematodes or yeast. In mammals, mitochondria play an important part in signalling apoptosis, which can either drive or retard ageing, depending on the cell type.

There is evidence that many longevity signals converge on members of the FOXO and sirtuin protein families, which can interact. Effects of FOXO and SIR2 in cells can be either beneficial (for example, increasing antioxidant defence) or detrimental (for example, apoptosis), and may or may not promote organismal survival. Apoptosis can be beneficial, for example, by eliminating damaged cells and preventing cancer, or can be detrimental, by eliminating irreplaceable cells, such as neurons.

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