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• W2048776985 abstract "Metabolism and ageing are intimately linked. Compared with ad libitum feeding, dietary restriction consistently extends lifespan and delays age-related diseases in evolutionarily diverse organisms. Similar conditions of nutrient limitation and genetic or pharmacological perturbations of nutrient or energy metabolism also have longevity benefits. Recently, several metabolites have been identified that modulate ageing; however, the molecular mechanisms underlying this are largely undefined. Here we show that α-ketoglutarate (α-KG), a tricarboxylic acid cycle intermediate, extends the lifespan of adult Caenorhabditis elegans. ATP synthase subunit β is identified as a novel binding protein of α-KG using a small-molecule target identification strategy termed drug affinity responsive target stability (DARTS). The ATP synthase, also known as complex V of the mitochondrial electron transport chain, is the main cellular energy-generating machinery and is highly conserved throughout evolution. Although complete loss of mitochondrial function is detrimental, partial suppression of the electron transport chain has been shown to extend C. elegans lifespan. We show that α-KG inhibits ATP synthase and, similar to ATP synthase knockdown, inhibition by α-KG leads to reduced ATP content, decreased oxygen consumption, and increased autophagy in both C. elegans and mammalian cells. We provide evidence that the lifespan increase by α-KG requires ATP synthase subunit β and is dependent on target of rapamycin (TOR) downstream. Endogenous α-KG levels are increased on starvation and α-KG does not extend the lifespan of dietary-restricted animals, indicating that α-KG is a key metabolite that mediates longevity by dietary restriction. Our analyses uncover new molecular links between a common metabolite, a universal cellular energy generator and dietary restriction in the regulation of organismal lifespan, thus suggesting new strategies for the prevention and treatment of ageing and age-related diseases." @default.
• W2048776985 created "2016-06-24" @default.
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• W2048776985 date "2014-05-14" @default.
• W2048776985 modified "2023-10-06" @default.
• W2048776985 title "The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR" @default.
• W2048776985 cites W1486450190 @default.
• W2048776985 cites W1944127002 @default.
• W2048776985 cites W1964150693 @default.
• W2048776985 cites W1964976203 @default.
• W2048776985 cites W1966132436 @default.
• W2048776985 cites W1970637701 @default.
• W2048776985 cites W1973722927 @default.
• W2048776985 cites W1977767269 @default.
• W2048776985 cites W1982085282 @default.
• W2048776985 cites W1986525197 @default.
• W2048776985 cites W1994305081 @default.
• W2048776985 cites W1997510569 @default.
• W2048776985 cites W1999010280 @default.
• W2048776985 cites W2001695752 @default.
• W2048776985 cites W2002030208 @default.
• W2048776985 cites W2002741326 @default.
• W2048776985 cites W2005868568 @default.
• W2048776985 cites W2011859278 @default.
• W2048776985 cites W2018422556 @default.
• W2048776985 cites W2031323796 @default.
• W2048776985 cites W2034574579 @default.
• W2048776985 cites W2035016947 @default.
• W2048776985 cites W2040805319 @default.
• W2048776985 cites W2043738446 @default.
• W2048776985 cites W2048376025 @default.
• W2048776985 cites W2048967691 @default.
• W2048776985 cites W2053493267 @default.
• W2048776985 cites W2054550570 @default.
• W2048776985 cites W2055969029 @default.
• W2048776985 cites W2058484936 @default.
• W2048776985 cites W2061148345 @default.
• W2048776985 cites W2066727453 @default.
• W2048776985 cites W2069024509 @default.
• W2048776985 cites W2070719504 @default.
• W2048776985 cites W2071950147 @default.
• W2048776985 cites W2072780644 @default.
• W2048776985 cites W2076724288 @default.
• W2048776985 cites W2092527265 @default.
• W2048776985 cites W2099540110 @default.
• W2048776985 cites W2104431515 @default.
• W2048776985 cites W2109188407 @default.
• W2048776985 cites W2113636792 @default.
• W2048776985 cites W2119629514 @default.
• W2048776985 cites W2119711811 @default.
• W2048776985 cites W2123754932 @default.
• W2048776985 cites W2130757625 @default.
• W2048776985 cites W2131860315 @default.
• W2048776985 cites W2134138119 @default.
• W2048776985 cites W2143505819 @default.
• W2048776985 cites W2147501289 @default.
• W2048776985 cites W2148581106 @default.
• W2048776985 cites W2150419930 @default.
• W2048776985 cites W2163382569 @default.
• W2048776985 cites W2172993862 @default.
• W2048776985 cites W4238567307 @default.
• W2048776985 cites W2037426198 @default.
• W2048776985 doi "https://doi.org/10.1038/nature13264" @default.

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