Abstract
Cyclic adenosine monophosphate (cAMP) plays an important role in many biological processes as a second messenger, and cAMP treatment has been reported to extend the lifespan of wild-type Drosophila melanogaster. Our study showed that exogenous cAMP improved ageing-related phenotypes by increasing the protein level of Sirtuins, which prevented metabolic disorders to mimic the effect of calorie restriction. Experiments in vitro showed that cAMP directly bound to SIRT1 and SIRT3 and consequently increased their activity. These findings suggest that cAMP slows the ageing process and is a good candidate to mimic calorie restriction. Our research provides a promising therapeutic strategy to target metabolic disorder-induced ageing-related diseases.
Highlights
Calorie restriction is an effective intervention to extend both the average and maximum lifespan[1]
Our study shows that dietary Cyclic adenosine monophosphate (cAMP) supplements can up-regulate the protein level of Sirtuin to delay the onset of ageing-related phenotypes by preventing metabolic disorders
We demonstrated that cAMP could directly bind both SIRT1 and SIRT3 in vitro, increasing the activities of SIRT1 and SIRT3 and mimicking the effects of calorie restriction
Summary
Calorie restriction is an effective intervention to extend both the average and maximum lifespan[1]. The anti-ageing effect of calorie restriction calls for an approximately 30%–40% reduction in caloric intake, which is intolerable for most people. Many researchers have attempted to find a drug to mimic calorie restriction that has anti-ageing effects without reducing energy intake, such as resveratrol[2]. A recent study reported that resveratrol exerts anti-ageing effects by inhibiting cAMP hydrolysis. Rolipram, which inhibits cAMP hydrolysis, had similar effects as resveratrol[3], indicating the potential of cAMP as a candidate calorie restriction mimetic. Another study showed that the lifespan of wild-type Drosophila melanogaster significantly increased after cAMP treatment[4], suggesting that cAMP may play a pivotal role in delaying the ageing process of organisms
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