2014
DOI: 10.18632/aging.100687 View full text |Buy / Rent full text
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Abstract: Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) or GDF15 is a divergent member of the transforming growth factor beta (TGF-β) superfamily and mice expressing hNAG-1/hGDF15 have been shown to be resistant to HFD-induced obesity and inflammation. This study investigated if hNAG-1 increases lifespan in mice and its potential mechanisms. Here we report that female hNAG-1 mice had significantly increased both mean and median life spans in two transgenic lines, with a larger difference in life spans in mi… Show more

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“…DUSP10 preferentially dephosphorylates p38 MAPK [49]. Growth differentiation factor 15 ( GDF15 ) was the top upregulated AMPK-independent gene (Fig 2B) and its overexpression is known to result in improved insulin sensitivity [50]. The transporter solute carrier family 19, member 3 ( SLC19A3 ) was also an upregulated AMPK-dependent gene (S1 Table), and is known to play a role in the intestinal absorption and tissue distribution of metformin [51].…”
Section: Discussionmentioning
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“…DUSP10 preferentially dephosphorylates p38 MAPK [49]. Growth differentiation factor 15 ( GDF15 ) was the top upregulated AMPK-independent gene (Fig 2B) and its overexpression is known to result in improved insulin sensitivity [50]. The transporter solute carrier family 19, member 3 ( SLC19A3 ) was also an upregulated AMPK-dependent gene (S1 Table), and is known to play a role in the intestinal absorption and tissue distribution of metformin [51].…”
Section: Discussionmentioning
“…Several recent reports have shown the association of GDF15 with aging and longevity. Female transgenic mice overexpressing human GDF15 in various tissues, such as skin, colon, kidney, brain and adipose tissues, present a prolongation of both mean and median lifespans, and the effects are more prominent in mice fed a high‐fat diet than in those fed a low‐fat diet . In contrast, several epidemiological studies have shown an association between GDF15 and all‐cause mortality.…”
Section: Agingmentioning
“…Notably, we here show that the induction of Gdf15 was not affected by the loss of FGF21 action. It was previously shown that overexpression of Gdf15 in mice prevents dietinduced obesity and increases lifespan by activating adipose tissue as well as systemic energy metabolism [66,67]. Conversely, circulating levels of GDF15 are also highly elevated in patients with muscle atrophy [68] and in cancer patients with severe anorexia and weight loss [69] and chronic inflammation [70].…”
Section: Discussionmentioning