CYCLIC AMP SKIN
CYCLIC AMP ACTIVATOR

The red line indicates the angle of the mouse spine. ( A) The appearance of aged mice (24-month-old) with (right) or without (left) db-cAMP treatment. These results explain why cAMP-treated mice exhibited improved appearance and show that cAMP treatment can delay the onset of ageing-related phenotypes.ĬAMP Treatment Mimics the Calorie Restriction Effect to Improve Ageing-associated Phenotypes in Aged Mice.

Because ROS accumulation is one of the causes of ageing-related phenotypes 14, we assessed ROS-related damage to proteins and lipids in mouse livers and found that cAMP treatment can significantly reduce the amount of carbonyl and MDA levels in aged mice ( Fig.

CYCLIC AMP SKIN

In the skin of aged mice, the collagen and muscle tissue was reduced, which could be restored by cAMP treatment ( Fig. As observed from tissue sections, liver hydropic degeneration was more severe in untreated aged mice compared with the cAMP-treated group ( Fig. Because cAMP signalling enhancers have been reported as a companion therapy in the treatment of cognitive dysfunction 13, we performed a behavioural test and the results showed, consistent with the mice’s appearance, that cAMP treatment improved behavioural performance in aged mice, including learning and memory, local motor activity, motor coordination and muscular strength ( Fig. Compared with the untreated group, the average lifespan of cAMP treated mice was extended by 6 weeks (4%, Fig. As observed from their appearance, cAMP treatment improved ageing-related phenotypes in aged mice, including thicker hair, stronger body and straighter spine ( Fig.

To study the potential role of cAMP in the ageing process, we administered cAMP (20 mg per kg diet) to young (3-month-old) and aged (21-month-old) mice for 3 months. The results showed that cAMP could directly combine with SIRT1/SIRT3, suggesting that cAMP has an anti-ageing effect and is a good candidate for a calorie restriction mimetic.Įxogenous cAMP Improves the Ageing-associated Phenotype in Aged Mice Our study showed that administration of exogenous cAMP (dibutyryl cyclic adenosine, db-cAMP) increased the protein level of Sirtuin to mimic the anti-ageing effects of calorie restriction, including the prevention of metabolic disorders and improvement in ageing-related phenotypes. In addition, there is an independent system to regulate the formation and degradation of cAMP in mitochondria to control ROS generation 10, 11, but whether cAMP can regulate SIRT3 to reduce oxidative stress has not been reported.ĬAMP performs a variety of metabolic-related hormone signalling processes as a second messenger and the cAMP response for many hormones becomes blunted with ageing 12, suggesting that there should be an important role for cAMP in the regulation of the ageing process. SIRT3, as a SIRT1 homologous deacetylase, is mainly located in mitochondria, where it reduces the amount of reactive oxygen species (ROS) responsible for inducing cell senescence 8, 9.

CYCLIC AMP ACTIVATOR

These findings highlighted the relationship between cAMP and SIRT1 in different pathways and suggested the potential of cAMP to be a specific activator of SIRT1 and mimic the anti-ageing effect of calorie restriction. Another study showed that the activation of the cAMP-PKA signalling pathway led to rapid SIRT1 phosphorylation, without changing the NAD + level 7. A recent study showed that cAMP activated calmodulin kinase kinase II (CaMKKII) to increase the AMPK phosphorylation level, thus promoting NAD + production and SIRT1 activation 3. It has been reported that cAMP responsive-element binding (CREB) deficiency reduces the expression of SIRT1 CREB directly regulates the transcription of Sirt1 in neuronal cells by binding to Sirt1 chromatin 6. SIRT1 has been proposed as an anti-ageing protein and its activation results in health benefits in multiple organisms 5. 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.

Rolipram, which specifically inhibits cAMP hydrolysis, had similar effects as resveratrol 3, indicating the potential of cAMP as a candidate calorie restriction mimetic. A recent study reported that resveratrol exerts anti-ageing effects by inhibiting cAMP hydrolysis. 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. However, the anti-ageing effect of calorie restriction calls for an approximately 30%–40% reduction in caloric intake, which is intolerable for most people. Calorie restriction is an effective intervention to extend both the average and maximum lifespan 1.

Cyclic amp